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Shi B, Ye J, Chen W, Liao B, Gu W, Yin H, Lyu J. Prognosis of critically ill patients with early and late sepsis-associated acute kidney injury: an observational study based on the MIMIC-IV. Ren Fail 2025; 47:2441393. [PMID: 39980278 PMCID: PMC11849006 DOI: 10.1080/0886022x.2024.2441393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 12/04/2024] [Accepted: 12/08/2024] [Indexed: 02/22/2025] Open
Abstract
OBJECTIVE The Acute Disease Quality Initiative (ADQI) working group recently released a consensus definition of sepsis-associated acute kidney injury (SA-AKI), but the prognosis and risk factors for early and late SA-AKI have not been studied. METHODS This was a retrospective cohort study based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (v2.2). First, SA-AKI patients that met the new definition from the ADQI were screened, and then, the relationships between SA-AKI occurrence time and relevant clinical parameters were analyzed. RESULTS After propensity score matching, 1,090 early SA-AKI (AKI occurring within 48 h of sepsis diagnosis) cases and late SA-AKI (AKI occurring between 48 h and 7 days after sepsis diagnosis) cases were identified. Compared with late SA-AKI patients, early SA-AKI patients had no significant differences in all-cause mortality at 28 days, 60 days or 180 days, renal replacement therapy (RRT) rates; or major adverse kidney events at 30 days (MAKE-30). However, the renal recovery of early SA-AKI patients was significantly better than that of late SA-AKI patients, their lengths of hospital stay and intensive care unit stay were significantly shorter, and the number of patients with positive fluid balance was lower, but the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and nephrotoxic antibiotics and the incidence of septic shock were higher. In addition, there was a difference in the number of patients with early and late SA-AKI at highest AKI stages 1 and 3. Data analysis also revealed that liver disease, cancer, highest AKI stage 3 and septic shock were associated with renal nonrecovery. CONCLUSIONS Although there was no significant difference in mortality between early and late SA-AKI patients, there were significant differences in renal recovery, positive fluid balance, nephrotoxic antibiotic use, septic shock and AKI stage. Therefore, the classification of early and late SA-AKI has certain scientific and rational validity, but whether the two have different clinical outcomes and pathogeneses requires further study.
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Affiliation(s)
- Bowen Shi
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Jianfeng Ye
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Weisheng Chen
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Bojian Liao
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Wanjie Gu
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Haiyan Yin
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Jun Lyu
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, Guangdong, China
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Jiang S, Xu L, Wang X, Li C, Guan C, Che L, Wang Y, Shen X, Xu Y. Risk prediction for acute kidney disease and adverse outcomes in patients with chronic obstructive pulmonary disease: an interpretable machine learning approach. Ren Fail 2025; 47:2485475. [PMID: 40195585 PMCID: PMC11983531 DOI: 10.1080/0886022x.2025.2485475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 03/18/2025] [Accepted: 03/19/2025] [Indexed: 04/09/2025] Open
Abstract
BACKGROUND Little is known about acute kidney injury (AKI) and acute kidney disease (AKD) in patients with chronic obstructive pulmonary disease (COPD) and COPD mortality based on the acute/subacute renal injury. This study develops machine learning models to predict AKI, AKD, and mortality in COPD patients, utilizing web applications for clinical decisions. METHODS We included 2,829 inpatients from January 2016 to December 2018. Data were split into 80% for training and 20% for testing. Eight machine learning algorithms were used, and model performance was evaluated using various metrics. SHAP was used to visualize the decision process. The best models, assessed using AUROC were used to develop web applications for identifying high-risk patients. RESULTS The incidence rates were 13.71% for AKI and 15.11% for AKD. The overall mortality rate was 4.84%. LightGBM performed best with AUROC of 0.815, 0.827, and 0.934 in AKI, AKD, and mortality, respectively. Key predictors for AKI were Scr, neutrophil percentage, cystatin c, BUN, and LDH. For AKD, the key predictors were age, AKI grade, HDL-C, Scr, and BUN. The key predictors for mortality included the use of dopamine and epinephrine drugs, cystatin c, renal function trajectory, albumin, and neutrophil percentage. Force plots visualized the prediction process for individual patients. CONCLUSIONS The incidence of AKI and AKD is significant in patients with COPD. Renal function trajectory is crucial for predicting mortality in these patients. Web applications were developed to predict AKI, AKD, and mortality, improving prognosis by identifying high-risk patients and reducing adverse events and disease progression.
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Affiliation(s)
- Siqi Jiang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lingyu Xu
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xinyuan Wang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chenyu Li
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
- Division of Nephrology, Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Munich, Germany
| | - Chen Guan
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lin Che
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yanfei Wang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xuefei Shen
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yan Xu
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
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Xie B, Ye N, Wang G, Cheng H. Factors influencing early renal function changes after SGLT2 inhibitors use and its long-term prognosis: a real-world retrospective study. Ren Fail 2025; 47:2496980. [PMID: 40289726 PMCID: PMC12039407 DOI: 10.1080/0886022x.2025.2496980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 02/28/2025] [Accepted: 04/13/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND The renal protective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been confirmed. However, SGLT2i may lead to an increase in serum creatine shortly after administration. This study explores the factors influencing this change and its impact on long-term renal function. METHODS We retrospectively studied patients starting SGLT2i treatment, classifying them into kidney function deterioration (RD) and non-deterioration (non-RD) groups based on three-month serum creatinine changes. Multivariate logistic regression identified factors influencing RD, and mixed-effects linear models evaluated eGFR slope changes. RESULTS A total of 544 patients were included, with 78 (14.3%) in the RD group and 466 (85.7%) in the non-RD group. Lower eGFR and serum albumin are independent risk factors for RD. With the decrease of eGFR by 10 mL/min/1.73㎡, the risk of RD increased by 42.3% (p < .001). With the decrease of serum albumin by 5 g/L, the risk of RD increased by 41.7% (p < .001). The maximum difference in eGFR between the RD and non-RD groups was 13.88 mL/min/1.73 m2 (95%CI, 9.99 to 17.78; p < .001) on two months. One year after medication, the difference in eGFR was not related to whether RD occurred (p ≥ .05). During the first three months post-medication, the difference in the eGFR slope between the two groups was 40.51 mL/min/1.73 m2 per year (95%CI, 27.43 to 53.60; p < .001). Over three years, the difference in the eGFR slope was 0.59 mL/min/1.73 m2 per year (95%CI, -0.69 to 1.88; p > .05). CONCLUSIONS While some experiences an increase in serum creatine, there is no significant long-term difference in renal function between the two groups.
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Affiliation(s)
- Bing Xie
- Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Nan Ye
- Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Guoqin Wang
- Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Hong Cheng
- Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
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Xia X, Liu R, Jiang X. Integration of mitochondrial gene expression and immune landscape in acute kidney injury prediction. Ren Fail 2025; 47:2502608. [PMID: 40369940 PMCID: PMC12082736 DOI: 10.1080/0886022x.2025.2502608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2025] [Revised: 04/17/2025] [Accepted: 05/01/2025] [Indexed: 05/16/2025] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a life-threatening condition with limited early biomarkers. Mitochondrial dysfunction is central to AKI pathophysiology, yet its potential for predicting AKI remains underexplored. METHODS Gene expression data from three publicly available AKI datasets (GSE30718, GSE61739, and GSE139061) were analyzed to identify differentially expressed genes (DEGs). A set of 11 mitochondrial-related genes was selected and used to construct a mitochondrial risk score (MRS) model via Lasso and elastic net regression. The model was validated across multiple datasets. Immune infiltration was assessed using the xCell algorithm to explore the relationship between MRS and immune cell dynamics in AKI. Stable HK-2 cells were constructed of XRCC3 knockdown and overexpression to investigate the effects of XRCC3 on cell activities. Additionally, the impact of XRCC3 on mitochondrial structure and function was examined in vivo and in vitro. RESULTS Eleven mitochondrial-related genes were consistently dysregulated across all datasets. PCA demonstrated a clear separation between AKI and normal samples. Functional enrichment analysis revealed that upregulated genes were linked to extracellular matrix remodeling and stress responses, while downregulated genes were associated with mitochondrial dysfunction. The MRS model showed strong predictive performance. We found that XRCC3 significantly promoted the activities of HK-2 cells and improved the integrity of mitochondrial structure and function in vivo and in vitro. CONCLUSION The mitochondrial gene-based MRS model is a robust tool for predicting AKI. Our findings underscore the critical role of mitochondrial dysfunction and immune modulation in AKI, offering potential avenues for targeted therapeutic strategies.
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Affiliation(s)
- Xiaoping Xia
- Department of Intensive Care Unit, Taizhou Integrated Traditional Chinese and Western Medicine Hospital, Wenling, Zhejiang, China
| | - Renyang Liu
- Emergency and Critical Care Center, Intensive Care Unit, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Xiaohui Jiang
- Emergency and Critical Care Center, Intensive Care Unit, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
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Chen L, Cheng Y, Bu X, Zhang C, Sun J, Liu X, Kong S, Ge Y, Shi H, Zhou J. Intraoperative hemodynamics in prediction of postoperative kidney injury after type a aortic dissection surgery: a retrospective cohort study. Ann Med 2025; 57:2474859. [PMID: 40042458 PMCID: PMC11884094 DOI: 10.1080/07853890.2025.2474859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 02/12/2025] [Accepted: 02/18/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND Type A aortic dissection (TAAD) is a severe cardiovascular condition associated with high risks for postoperative complications, particularly renal dysfunction. This study investigated whether intraoperative hypotension and venous congestion are important predictors of postoperative kidney injury and major adverse events. METHODS We retrospectively analyzed 543 adults undergoing TAAD surgery (2016-2023). Primary outcomes were acute kidney injury (AKI) and acute kidney disease (AKD). Secondary outcomes included death, stroke and composite outcome. Patients were divided into four groups: AKI only, AKD only, AKI and AKD, Non-AKI or AKD. We used restricted cubic spline and multivariate logistic regression models to adjust for confounding factors. RESULTS AKI or AKD was significantly associated with each 10-minute epoch of central venous pressure (CVP) ≥10, 12, 16, 20 mmHg (all p < 0.001), with each 60-minute epoch of CVP ≥10, 12, 16, 20 mmHg area under the curve (AUC) (all p < 0.001). Regarding death, a 6% to 13% increase rate for each 10-minute epoch of CVP ≥10, 12, 16, 20 mmHg (all p ≤ 0.003), a 5% to 21% increase for each 60-minute epoch of CVP ≥10, 12, 16, 20 mmHg AUC (all p < 0.001). In terms of stroke risk, a 5% increase rate for every 10-minute increase in the CVP AUC above 16 mmHg, and an 11% increased risk for CVP AUC above 20 mmHg (p = 0.039 and p = 0.031, respectively). CONCLUSION Elevated CVP and lower MAP levels were linked to postoperative AKI and AKD risk. CVP showed stronger associations with mortality and stroke. Optimizing perioperative hemodynamic management may improve individualized interventions.
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Affiliation(s)
- Lihai Chen
- Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yi Cheng
- School of International Business, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Xinyi Bu
- Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Chen Zhang
- Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jie Sun
- Department of Anesthesiology, Zhongda Hospital, Southeast University, Nanjing, China
| | - Xuesheng Liu
- Department of Anesthesiology, First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Siyu Kong
- School of International Business, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Yali Ge
- Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Hongwei Shi
- Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jifang Zhou
- School of International Business, China Pharmaceutical University, Nanjing, Jiangsu, China
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Lin H, Pan J, Zhang J, He Y, Ge Y, Niu D, Han W, Han X, Li F, Bai X, Feng X, Lin L, Shen R, Su X, Qiao X. Intermedin protects peritubular capillaries by inhibiting eNOS uncoupling through AMPK/GTPCH-I/BH4 pathway and alleviate CKD following AKI. Free Radic Biol Med 2025; 234:72-85. [PMID: 40228707 DOI: 10.1016/j.freeradbiomed.2025.04.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 03/26/2025] [Accepted: 04/08/2025] [Indexed: 04/16/2025]
Abstract
BACKGROUND Even after recovery of kidney function following AKI, progression to CKD may still occur, characterized by a reduction in peritubular capillaries (PTC) and subsequent kidney fibrosis. Reactive oxygen species (ROS) from uncoupled eNOS are suspected to damage endothelial cells and cause PTC rarefaction observed in AKI-CKD. Intermedin (IMD) inhibits eNOS uncoupling by activating AMPK, but its impact on AKI-CKD transition remains unclear. METHODS We utilized IMD-deficient (IMD-/-) mice to explore its effects on AKI-CKD transition, PTC density, endothelial damage, and kidney ROS in a kidney ischemia/reperfusion injury (IRI) model. To elucidate its protective mechanism for PTCs, we subsequently investigated the effects of IMD on endothelial cells and ROS using a hypoxia/reoxygenation (HR) model with human umbilical vein endothelial cells (HUVECs). Finally, we investigated the influence of IMD on AMPK/GTPCH-I/BH4/eNOS to explore its mechanism in alleviating oxidative stress. RESULTS Compared with IMD+/+ littermate sham controls, PTC density was significantly reduced in IMD-/- sham mice, with significantly increased oxidative stress. Post-AKI, both IMD+/+ and IMD-/- mice demonstrated substantial declines in kidney function and histology, along with significant fibrosis, PTC reduction, and heightened oxidative stress. Moreover, the severity of kidney damage in IMD-/- mice following AKI was considerably more pronounced than in IMD+/+ mice. HR significantly induced eNOS uncoupling and oxidative stress in HUVECs. Treatment with IMD effectively inhibited eNOS uncoupling and ROS production, achieving levels comparable to the antioxidant N-acetylcysteine. The inhibitory effect of IMD on eNOS uncoupling was abrogated when L-NAME was introduced after HR. HR significantly impaired AMPK activation, which could be reversed by IMD. Additional experiments with inhibitors of GTPCH-I and AMPK, and exogenous BH4, confirmed that IMD protects endothelial cells by activating AMPK/GTPCH-I/BH4, thereby inhibiting eNOS uncoupling and ROS production. CONCLUSION We concluded that IMD inhibits AKI-CKD transition by protecting endothelial cells of PTC via AMPK/GTPCH-I/BH4/eNOS pathway.
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Affiliation(s)
- Hui Lin
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Juan Pan
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Junhua Zhang
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Yuyin He
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Yuan Ge
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Dan Niu
- Department of Pathology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Weixia Han
- Department of Pathology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Xiaoli Han
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Fan Li
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Xiaomei Bai
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Xinyuan Feng
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Ling Lin
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Ruihua Shen
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Xiaole Su
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China
| | - Xi Qiao
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China; Shanxi Kidney Disease Institute, Taiyuan, People's Republic of China; Kidney Research Center of Shanxi Medical University, Taiyuan, People's Republic of China.
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Raymakers-Janssen PAMA, van den Berg G, Lilien MR, van Kessel IA, van der Steeg AFW, Wijnen MHWA, Triest MI, van Peer SE, Jongmans MCJ, van Tinteren H, Janssens GO, Fiocco M, Wösten-van Asperen RM, van den Heuvel-Eibrink MM. The incidence and outcome of acute kidney injury during pediatric kidney tumor treatment-a national cohort study. Pediatr Nephrol 2025; 40:2393-2401. [PMID: 39966140 PMCID: PMC12116620 DOI: 10.1007/s00467-025-06684-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 12/30/2024] [Accepted: 12/30/2024] [Indexed: 02/20/2025]
Abstract
BACKGROUND Acute kidney injury (AKI) is a serious complication of pediatric cancer treatment that is suggested to increase the risk of chronic kidney disease (CKD). Children with a kidney tumor may be at particular risk. This study aimed to determine the incidence and risk factors of AKI and its association with CKD during pediatric kidney tumor treatment. METHODS We analyzed data from a prospective national cohort of patients ≤ 18 years old diagnosed with a kidney tumor between 2015 and 2021 in the Princess Máxima Center for Pediatric Oncology in the Netherlands. AKI was defined according to KDIGO criteria. CKD was assessed 1 year post-treatment based on proteinuria and/or decreased estimated glomerular filtration rate (eGFR). RESULTS Of 147 patients, we observed AKI in 104 patients (71%) during therapy. AKI occurred most often within 48 h after tumor nephrectomy (88/104), while the rest had non-nephrectomy-related AKI from multifactorial causes. Sixteen patients experienced more than one AKI episode, and 92/104 episodes were reversible. Patients who developed AKI had a higher eGFR prior to surgery compared to those who did not develop AKI. CKD was observed in 16/120 patients (13%). Risk factors for developing CKD included the occurrence of at least 1 AKI event, the use of a > 3-drug regimen, and a lower eGFR at the start of treatment. CONCLUSION The high incidence of AKI and its association with early CKD highlights the need for early detection, prevention, and intervention strategies during pediatric kidney tumor treatment.
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Affiliation(s)
- Paulien A M A Raymakers-Janssen
- Department of Pediatric Intensive Care, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
- Princess Máxima Center for Pediatric Oncology and Wilhelmina Children's Hospital, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands.
| | - Gerrit van den Berg
- Princess Máxima Center for Pediatric Oncology and Wilhelmina Children's Hospital, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
- Department of Pediatric Nephrology, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands
| | - Marc R Lilien
- Department of Pediatric Nephrology, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands
| | - Inge A van Kessel
- Department of Pediatric Intensive Care, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands
| | - Alida F W van der Steeg
- Princess Máxima Center for Pediatric Oncology and Wilhelmina Children's Hospital, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
| | - Marc H W A Wijnen
- Princess Máxima Center for Pediatric Oncology and Wilhelmina Children's Hospital, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
| | - Mieke I Triest
- Princess Máxima Center for Pediatric Oncology and Wilhelmina Children's Hospital, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
| | - Sophie E van Peer
- Princess Máxima Center for Pediatric Oncology and Wilhelmina Children's Hospital, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
| | - Marjolijn C J Jongmans
- Princess Máxima Center for Pediatric Oncology and Wilhelmina Children's Hospital, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
| | - Harm van Tinteren
- Princess Máxima Center for Pediatric Oncology and Wilhelmina Children's Hospital, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
| | - Geert O Janssens
- Princess Máxima Center for Pediatric Oncology and Wilhelmina Children's Hospital, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Marta Fiocco
- Princess Máxima Center for Pediatric Oncology and Wilhelmina Children's Hospital, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
- Mathematical Institute, Leiden University, Leiden, The Netherlands
- Department of Biomedical Science, Medical Statistical Section, Leiden University Medical Centre, Leiden, The Netherlands
| | - Roelie M Wösten-van Asperen
- Department of Pediatric Intensive Care, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands
| | - Marry M van den Heuvel-Eibrink
- Princess Máxima Center for Pediatric Oncology and Wilhelmina Children's Hospital, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands
- Wilhelmina Children's Hospital/University Medical Center Utrecht, Theme Child Health, Utrecht, The Netherlands
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Ye C, Zhu C, Hu S, Mei Y, Yang T. A study on the factors influencing mortality risk in sepsis-induced acute kidney injury based on analysis of the MIMIC database. Clin Exp Med 2025; 25:192. [PMID: 40481893 PMCID: PMC12145314 DOI: 10.1007/s10238-025-01681-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Accepted: 04/12/2025] [Indexed: 06/11/2025]
Abstract
Sepsis-induced acute kidney injury (SA-AKI) significantly increases mortality and healthcare burdens. Identifying key mortality risk factors is crucial for improving patient outcomes. This study aims to identify the primary factors affecting mortality in SA-AKI patients using the MIMIC-III database. A retrospective analysis was conducted on 4868 SA-AKI patients from the MIMIC-III database. Clinical data from the first 24 h of ICU admission were analyzed using logistic regression to identify mortality predictors. Key mortality predictors included advanced age (OR = 1.015, 95% CI: 1.006-1.024), severe AKI stages (OR = 1.470, 95% CI: 1.285-1.676), low serum albumin (OR = 0.606, 95% CI: 0.506-0.722), delayed antibiotics (OR = 1.001, 95% CI: 1.000-1.002), high AST (OR = 1.035, 95% CI: 1.027-1.083), and bilirubin (OR = 1.055, 95% CI: 1.037-1.083). The area under the curve (AUC) of the combined predictors for mortality risk was 0.796, indicating high predictive accuracy. Conclusions: Early intervention and monitoring of identified risk factors such as age, AKI stage, albumin levels, and antibiotic timeliness can enhance survival rates in SA-AKI patients.
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Affiliation(s)
- Chongyang Ye
- Department of Critical Care Medicine, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of science and Technology of China, Hefei, Anhui Province, 230001, China
| | - Chunyan Zhu
- Department of Critical Care Medicine, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of science and Technology of China, Hefei, Anhui Province, 230001, China
| | - Shijing Hu
- Department of Critical Care Medicine, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of science and Technology of China, Hefei, Anhui Province, 230001, China
| | - Yulin Mei
- Department of Critical Care Medicine, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of science and Technology of China, Hefei, Anhui Province, 230001, China
| | - Tianjun Yang
- Department of Critical Care Medicine, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of science and Technology of China, Hefei, Anhui Province, 230001, China.
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9
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Nagalingam K, Whiting L, Farrington K, Migliozzi J, Pattison N. Clinical Assessment of Fluid Status in Adults With Acute Kidney Injury: A Scoping Review. J Ren Care 2025; 51:e70014. [PMID: 40186545 PMCID: PMC11971954 DOI: 10.1111/jorc.70014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 03/05/2025] [Accepted: 03/19/2025] [Indexed: 04/07/2025]
Abstract
BACKGROUND Acute kidney injury refers to sudden, potentially reversible, reduction in kidney function. Hypovolaemia is commonly the major risk factor. When acute kidney injury is established, fluid can accumulate leading to fluid overload. Undertaking a rigorous fluid assessment is vital in the management of a patient in hospital with acute kidney injury, as insufficient or excessive fluid can lead to increased morbidity and mortality. OBJECTIVES The aim of this scoping review is to identify which clinical assessments are useful when undertaking fluid assessment in a patient with acute kidney injury, and to identify signs and symptoms of fluid overload or dehydration in patients in hospital with acute kidney injury. DESIGN The JBI methodology for scoping reviews was followed and reported using the PRISMA-ScR checklist. PubMed, CINAHL Plus and SCOPUS were searched for research papers relating to the signs and symptoms or fluid assessments in patients with acute kidney injury. RESULTS Fifteen research papers were identified with four key areas being: Fluid balance/urine output and weight; early warning scores; clinical signs and symptoms; holistic assessment. The primary studies included in this scoping review have shown that hypovolaemia may be indicated by low blood pressure, orthostatic hypotension, low Mean Arterial Pressure, elevated heart rate, prolonged capillary refill time on the sternum (> 4.5 s) and subjectively reported cold peripheries. With clinical symptoms including dry mouth, increased thirst and dry skin. Accurate documentation of urine output and fluid balance is crucial in determining fluid status. CONCLUSION The assessment of fluid should be holistic and include history taking, diagnosis, blood tests and associated clinical signs and symptoms.
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Affiliation(s)
- Karen Nagalingam
- University of HertfordshireHatfieldUK
- Lister Hospital, East and North Hertfordshire NHS TrustStevenageUK
| | | | - Ken Farrington
- University of HertfordshireHatfieldUK
- Lister Hospital, East and North Hertfordshire NHS TrustStevenageUK
| | | | - Natalie Pattison
- University of HertfordshireHatfieldUK
- Lister Hospital, East and North Hertfordshire NHS TrustStevenageUK
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10
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Li W, Dong C, Sun C, Wang K, Zheng W, Wei X, Han C, Yang Y, Wang Z, Cui G, Li L, Gao W. Combining Acute Kidney Injury Grading and Recovery Mode for Screening in Pediatric Liver Transplantation: A Retrospective Observational Study. Pediatr Transplant 2025; 29:e70089. [PMID: 40313057 DOI: 10.1111/petr.70089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 02/17/2025] [Accepted: 04/17/2025] [Indexed: 05/03/2025]
Abstract
BACKGROUND A growing number of studies indicate that acute kidney injury (AKI) and the pattern of recovery after kidney injury are associated with poor outcomes for grafts and long-term renal function after liver transplantation (LT). However, few systematic studies have been conducted on the pediatric liver transplantation (PLT) population. MATERIALS AND METHODS In this single-centered retrospective observational study, according to AKI degree and whether AKI was persistent, patients were divided into three groups: non-AKI/stage 1 AKI, stage 2/3 transient AKI, and stage 2/3 persistent AKI. We compared the survival of patients, graft, and chronic kidney disease (CKD) among the three groups, analyzing the risk factors for the stage 2/3 persistent AKI. RESULTS Among 700 patients, the total incidence of AKI was 39.57%; of children with stage 2/3 AKI, the condition was persistent in 38.06%. In the stage 2/3 persistent-AKI group, the risk of graft loss was 3.264× greater than in the no-AKI/stage 1 AKI group and 4.329× greater than in the stage 2/3 transient AKI group. Pediatric End-stage Liver Disease (PELD) score, preoperative estimated glomerular filtration rate (eGFR), duration of vena cava occlusion, postoperative respiratory support time, and postoperative early allograft dysfunction (EAD) were significantly correlated with the occurrence of stage 2/3 persistent AKI. CONCLUSIONS By combining AKI recovery mode with AKI grading, clinicians can screen out stage 2/3 persistent AKI with a worse prognosis. This method was more accurate in predicting prognosis than applying AKI grading alone.
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Affiliation(s)
- Weihan Li
- The First Central Clinical School, Tianjin Medical University, Tianjin, China
| | - Chong Dong
- Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
| | - Chao Sun
- Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
| | - Kai Wang
- Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
| | - Weiping Zheng
- Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
| | - Xinzhe Wei
- Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
| | - Chao Han
- Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
| | - Yang Yang
- Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
| | - Zhen Wang
- Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
| | - Ganlin Cui
- The First Central Clinical School, Tianjin Medical University, Tianjin, China
| | - Linxiao Li
- The First Central Clinical School, Tianjin Medical University, Tianjin, China
| | - Wei Gao
- Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
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11
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Butz E, Schultheiss UT, Sekula P. Modelling heterogeneity in the progression of chronic kidney disease. Nephrol Dial Transplant 2025; 40:1107-1114. [PMID: 39701823 DOI: 10.1093/ndt/gfae288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Indexed: 12/21/2024] Open
Abstract
Cohort studies with comprehensive follow-up periods that track patients with chronic kidney disease (CKD) and gather extensive health data are important for understanding the diverse progression patterns of CKD. This review explores the potential of emerging analytical techniques that can be applied in addition to conventional analysis approaches to enhance CKD research by offering more detailed insights into disease progression. To maximize the insights available from CKD cohort data with extended follow-up, we examined two advanced approaches: analysis of disease trajectories and analysis of recurrent events. The analysis of trajectories examines the timing and relationships between events, uncovering progression patterns and identifying key events that could signal future outcomes. In contrast, the application of recurrent event analysis facilitates the examination of repeated occurrences of significant events, thereby providing a more nuanced understanding of the evolution of risk over time. Using data from the German Chronic Kidney Disease study, this review illustrates how these approaches can enhance conventional analyses. The application of these supplementary methodologies to CKD research has the potential to facilitate a transition towards a more personalized approach to patient care. The insights gained may inform the development of tailored treatment strategies and contribute to enhanced overall patient outcomes.
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Affiliation(s)
- Elena Butz
- Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
| | - Ulla T Schultheiss
- Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
- Department of Medicine IV, Nephrology and Primary Care, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany and
- Synlab, MVZ Humangenetik Freiburg GmbH, Freiburg, Germany
| | - Peggy Sekula
- Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
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12
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Kattna A, Singh L. Genistein as a renoprotective agent: mechanistic insights into antioxidant, anti-inflammatory, and fibrosis-regulating pathways. Mol Biol Rep 2025; 52:500. [PMID: 40411620 DOI: 10.1007/s11033-025-10603-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2025] [Accepted: 05/12/2025] [Indexed: 05/26/2025]
Abstract
Kidney diseases refer to a group of disorders that affect the structure and function of the kidneys, impairing their ability to filter waste products, excess fluids, and toxins from the blood. These diseases can be acute and chronic, and if left untreated, can lead to kidney failure. Their progression is closely associated with inflammation and oxidative stress. Key signaling cascades, such as TLR-4/MAPK and TLR-4/NF-κB, are instrumental in fostering renal inflammation. Excessive ROS production worsens kidney damage, whereas activation of the Nrf-2/ARE pathway mitigates this by enhancing antioxidant defense. Moreover, the TGF-β/Smad pathway is heavily implicated in driving renal fibrosis, a major factor in disease progression. Additionally, elevated uric acid levels exacerbate inflammatory signaling, thereby worsening renal injury and dysfunction. Current treatments for kidney diseases have several concerns, including the need for routine monitoring, side effects, and long-term regimens. Several natural compounds have shown promise in supporting kidney health by modulating these key molecular targets. Genistein is a naturally occurring isoflavone predominantly found in soybeans and soy-based products, such as tofu, soy milk, and tempeh. It has demonstrated beneficial effects in various renal disorders, including both acute and chronic conditions, by regulating key molecular mediators involved in tissue injury, fibrosis, and cellular defense mechanisms. These mediators include TLR-4, MAPK, NF-κB, TGF-β, Smads, ACE, angiotensin, SIRT1, Nrf-2, ROS, SERBP, JAK/STAT and cytokines, among others. Considering the potential of genistein in modulating these mediators, the current review investigates the mechanistic interactions among these mediators in mediating its renoprotective effects.
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Affiliation(s)
- Ayush Kattna
- University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India
| | - Lovedeep Singh
- University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India.
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13
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Karmakar S, Dasgupta D, Akhtar S, Poddar S, Giri PP, Tse Y, Sinha R. Progression of acute kidney injury to chronic kidney disease: a prospective cohort study. Pediatr Nephrol 2025:10.1007/s00467-025-06810-5. [PMID: 40397129 DOI: 10.1007/s00467-025-06810-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 04/03/2025] [Accepted: 04/29/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND Prospective studies on kidney outcomes in critically ill children with acute kidney injury (AKI) are scarce from low- and middle-income countries (LMIC). We conducted a pilot study to evaluate the continuum of transient AKI-persistent AKI-acute kidney disease (AKD) and chronic kidney disease (CKD). METHODS Children (1-18 years) admitted to our tertiary Pediatric Intensive Care Unit (PICU) and developing AKI with no known pre-existing kidney co-morbidities from January 2021 to June 2022 were included with follow up visits at 1 and 3 months after AKI onset. AKI and CKD were defined as per KDIGO 2012. At risk of CKD was defined by albuminuria, hypertension, estimated glomerular filtration rate (eGFR) 60-90 ml/kg/1.73 m2 or hyperfiltration (eGFR ≥ 150 ml/kg/1.73 m2). RESULTS Of 390 children, 15% (n = 57) developed AKI. 75% (n = 43) with AKI had underlying primarily non-kidney systemic etiology. Fourteen (25%) died at median 5 days (IQR 4-7) after admission, and three were lost to follow up after discharge. For the 40 AKI survivors with three months data, incidence of transient AKI was 40% (n = 16), persistent AKI 20% (n = 8), AKD 32% (n = 13), and CKD 8% (n = 3). In addition, 18% (n = 7) were at risk of CKD. 38% with AKI for > 48 h vs. 6% with AKI < 48 h developed CKD or were at risk of CKD (p = 0.025). All three AKI survivors who progressed to CKD had an underlying primarily kidney etiology and progressed from AKD to CKD. CONCLUSIONS In this LMIC study, kidney sequelae were high at 3 months among PICU AKI survivors. This pilot supports the need and feasibility of larger prospective trials in LMIC settings to understand outcomes for all children with AKI.
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Affiliation(s)
- Shreyashi Karmakar
- Division of Pediatric Nephrology, Institute of Child Health, Kolkata, India
| | - Deblina Dasgupta
- Division of Pediatric Nephrology, Institute of Child Health, Kolkata, India
| | - Shakil Akhtar
- Division of Pediatric Nephrology, Institute of Child Health, Kolkata, India
| | - Sanjukta Poddar
- Division of Pediatric Nephrology, Institute of Child Health, Kolkata, India
| | - Prabhas Prasun Giri
- Division of Pediatric Intensive Care, Institute of Child Health, Kolkata, India
| | - Yincent Tse
- Division of Pediatric Nephrology, Great North Children Hospital, Newcastle, UK
| | - Rajiv Sinha
- Division of Pediatric Intensive Care, Institute of Child Health, Kolkata, India.
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14
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Hong Y, An Q, Wang Z, Hu B, Yang Y, Zeng R, Yao Y. Multi-omics Analysis Reveals the Propagation Mechanism of Ferroptosis in Acute Kidney Injury. Inflammation 2025:10.1007/s10753-025-02311-7. [PMID: 40358793 DOI: 10.1007/s10753-025-02311-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 04/01/2025] [Accepted: 04/28/2025] [Indexed: 05/15/2025]
Abstract
Acute kidney injury (AKI) is a prevalent and critical clinical condition characterized by high morbidity and mortality. Recently, numerous studies have implicated ferroptosis, an iron-dependent programmed cell death process, in the pathophysiology of AKI. Despite this, the mechanism underlying the widespread occurrence of ferroptosis in AKI remains elusive. To address this, our study analyzed snRNA-seq data from AKI and healthy renal tissues. The analysis revealed notable differences in ferroptosis activity within proximal tubule (PT) cells of AKI patients, specifically highlighting a strong correlation between ferroptosis and the expression of genes GPX4, FTH1, and FTL. Spatial transcriptomics confirmed that the genes GPX4, FTH1, and FTL play a crucial role in driving ferroptosis propagation in AKI. Furthermore, utilizing a mouse model of bilateral renal ischemia-reperfusion injury, we validated the emergence of ferroptosis mediated by these key genes following AKI. The findings from our in vivo experiments were consistent with the spatial transcriptomics data. Chromatin accessibility and transcription factor analysis identified KLF6 as a repressor of ferroptosis-related genes. An in-depth analysis of PT revealed a subpopulation closely associated with ferroptosis. The cellular microenvironment within this subpopulation may regulate ferroptosis through the SPP1 signaling pathway, ultimately influencing the outcome of PT following AKI. In conclusion, this study elucidates the crucial role of GPX4, FTH1, and FTL in ferroptosis propagation during AKI and underscores the potential therapeutic benefits of targeting ferroptosis in the management of AKI.
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Affiliation(s)
- Yu Hong
- Department of Nephrology, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Qi An
- Department of Nephrology, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Zheng Wang
- Department of Nephrology, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Bin Hu
- Department of Nephrology, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Yi Yang
- Department of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
| | - Rui Zeng
- Department of Nephrology, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
- Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei, China.
| | - Ying Yao
- Department of Nephrology, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
- Department of Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
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15
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Adams T, Batte A, Polidoro R, Cordy RJ. Analysis of Serum Creatinine Data from Long-tailed and Rhesus Macaques to Assess Malaria-associated Acute Kidney Injury. Semin Nephrol 2025:151617. [PMID: 40348697 DOI: 10.1016/j.semnephrol.2025.151617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Malaria caused by the protozoan parasite Plasmodium is associated with vast morbidity and mortality worldwide. Among the serious clinical complications of this disease are acute kidney injury (AKI) and acute kidney disease (AKD), characterized by a decline in kidney function measurable by changes in serum creatinine. Research using nonhuman primates (NHPs) has revealed commonalities between NHPs and humans in malaria pathogenesis. Here, we perform a reanalysis of serum creatinine data from published studies on P. knowlesi malaria infections of long-tailed (natural host) and rhesus (nonnatural host) macaques to assess AKI and AKD. In rhesus macaques, despite receiving antimalarial treatment to reduce parasitemia, delayed onset of AKD occurred days to weeks post-treatment, showing a disconnect between parasitemia and AKD. While the high mortality of rhesus macaques prohibited a prolonged experimental design, the use of long-tailed macaques, naturally resistant to P. knowlesi, enabled longer time series studies and revealed more details about disease progression. Most long-tailed macaques, despite having a natural ability to control parasitemia, also exhibited a delayed onset of AKD in the period following peak parasitemia. Altogether, this study shows that both rhesus and long-tailed macaques exhibit a delayed onset of AKD during malaria, as has been reported in humans.
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Affiliation(s)
- Tryphena Adams
- Department of Biology, Wake Forest University, Winston-Salem, NC, USA
| | - Anthony Batte
- Child Health and Development Center, College of Health Sciences, Makerere University, Kampala, Uganda; Medicine and Translational Research program, University of Barcelona, Barcelona, Spain
| | - Rafael Polidoro
- Ryan White Center for Pediatric Infectious Diseases and Global Health, Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
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16
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Shigidi MMT. Evaluating the use of tunneled hemodialysis catheters in the treatment of acute kidney disease patients requiring hemodialysis: a case-control study. Int Urol Nephrol 2025; 57:1609-1614. [PMID: 39572516 DOI: 10.1007/s11255-024-04292-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 11/12/2024] [Indexed: 04/17/2025]
Abstract
PURPOSE Tunneled hemodialysis catheters (TDCs) are increasingly used in the emergency management of severe acute kidney disease (AKD). This study aimed to evaluate the effectiveness of TDCs in AKD patients requiring hemodialysis. METHODS A case-control study was conducted in Khartoum, Sudan between February and September 2020. Adult patients admitted to the Baraha Medical City Intensive Care Unit with AKD due to non-infectious causes, and requiring hemodialysis were enrolled. Patients were randomly assigned to undergo hemodialysis using either tunneled or non-tunneled hemodialysis catheters (NTDCs). The performance and complications associated with TDCs were assessed during the hospital stay, after discharge, and until catheter removal. Data were analyzed using SPSS. RESULTS A total of 122 patients with a mean age of 60.4 ± 5.7 years were included. AKD was primarily due to acute tubular necrosis (67.2%) and interstitial nephritis (16.4%). Indications for hemodialysis were mostly acute pulmonary edema (64.8%) and symptomatic uremia (27.9%). TDCs were used in 54 (44.3%) patients, while NTDCs were used in 68 (55.7%). The right internal jugular vein was the most common insertion site (95.9%). TDCs were associated with significantly higher blood flow (P < 0.0001) and lower rates of exit site infections (P = 0.034), catheter-related bacteremia (P = 0.011), and catheter malfunction (P = 0.001). They showed a significantly longer functional duration compared to NTDCs (P < 0.0001). CONCLUSION TDCs appear to be a safer and more effective option for AKD patients requiring urgent and prolonged hemodialysis, with fewer complications and longer catheter function.
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Affiliation(s)
- Mazin M T Shigidi
- Department of Internal Medicine, College of Medicine, Jouf University, 72388, Al Jouf, Saudi Arabia.
- Nephrology Division, Department of Medicine, Baraha Medical City, Khartoum North, Khartoum State, Sudan.
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Vijayan A, Heung M, Awdishu L, Babroudi S, Green GB, Koester L, McCoy IE, Menon S, Palevsky PM, Proctor LA, Selewski DT, Struthers SA. ASN Kidney Health Guidance on the Outpatient Management of Patients with Dialysis-Requiring Acute Kidney Injury. J Am Soc Nephrol 2025; 36:926-939. [PMID: 40014384 PMCID: PMC12059106 DOI: 10.1681/asn.0000000646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025] Open
Abstract
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2025_03_11_KTS_March2025.mp3
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Affiliation(s)
- Anitha Vijayan
- Intermountain Health Kidney Services, Intermountain Health, Salt Lake City, Utah
| | - Michael Heung
- Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Linda Awdishu
- Division of Clinical Pharmacy, University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, California
| | - Seda Babroudi
- Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts
| | - Gopa B. Green
- U.S. Renal Care, Inc., Plano, Texas
- Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - Lisa Koester
- Division of Nephrology, Washington University School of Medicine, St. Louis, Missouri
| | - Ian E. McCoy
- Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California
| | - Shina Menon
- Division of Nephrology, Department of Pediatrics, Stanford University, Palo Alto, California
| | - Paul M. Palevsky
- Kidney Medicine Section, Medical Service, VA Pittsburgh Healthcare System and Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Lorri A. Proctor
- Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - David T. Selewski
- Division of Nephrology, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
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18
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Tan BW, Tan BW, Akalya K, Hong WZ, Da Y, Low S, Ng WY, Chua HR. Effect of Post-Acute Kidney Injury Use of Renin-Angiotensin Inhibitors on Long-term Mortality and Major Adverse Kidney Events: A 5-year Retrospective Observational Cohort Study. Kidney Med 2025; 7:100996. [PMID: 40321973 PMCID: PMC12049942 DOI: 10.1016/j.xkme.2025.100996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/08/2025] Open
Abstract
Rationale & Objective Acute kidney injury (AKI) is common in hospitalized adults and a risk factor for chronic kidney disease and mortality. The effect of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) post-AKI on mortality and long-term kidney function remains unclear. Study Design Propensity-weighted retrospective observational cohort study. Setting & Participants A total of 3,289 patients with AKI admitted to a tertiary care hospital from November 2015-October 2016, with follow-up until September 2020. Exposures ACEi/ARB use within 180 days post-AKI. Outcomes All-cause mortality, and major adverse kidney events (MAKE) as defined by composite of renal replacement therapy post-AKI, sustained estimated glomerular filtration rate (eGFR) decline >30% from baseline, or eGFR ≤15 mL/min/1.73 m2. Analytical Approach We generated propensity weights for ACEi/ARB use post-AKI, using age, sex, comorbid conditions, prior medication, intensive care unit admission, severe sepsis, and index AKI Kidney Disease: Improving Global Outcomes severity. Cox proportional hazard models were used to test associations of post-AKI ACEi/ARB with mortality, MAKE, and joint models for eGFR slopes. Results A total of 2,309 (70.2%) participants died or experienced MAKE by end of follow-up. 161 (4.9%) and 406 (12.3%) patients initiated or resumed prior ACEi/ARB use within 180 days post-AKI, respectively. Although the overall cohort had no significant mortality association with post-AKI ACEi/ARB use, a significant association with lower mortality was observed in patients with KDIGO 3 AKI (HR, 0.40; 95% CI, 0.21-0.75; P interaction = 0.003). However, post-AKI ACEi/ARB use was associated with increased MAKE in patients without cardiovascular indications for ACEi/ARB use (HR, 1.52; 95% CI, 1.17-1.98; P interaction = 0.03). Although post-AKI use of ACEi/ARB was associated with acute eGFR decline (initial eGFR change -2.3 mL/min/1.73 m2/year; 95% CI, -3.1 to -1.5; P < 0.001), no association with longer-term eGFR decline was observed. Limitations Retrospective observational study on heterogeneous AKI cohort without data on ACEi/ARB cumulative exposure. Conclusions Early ACEi/ARB post-AKI was not associated with better long-term survival or kidney function but was associated with lower mortality in patients with KDIGO 3 AKI.
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Affiliation(s)
- Byorn W.L. Tan
- Department of Medicine, National University Hospital, Singapore
| | - Bryce W.Q. Tan
- Department of Medicine, National University Hospital, Singapore
| | - K. Akalya
- Division of Nephrology, Department of Medicine, National University Hospital, Singapore
| | - Wei-Zhen Hong
- Division of Nephrology, Department of Medicine, National University Hospital, Singapore
- Fast and Chronic Programmes, Department of Medicine, Alexandra Hospital, Singapore
| | - Yi Da
- Division of Nephrology, Department of Medicine, National University Hospital, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Sanmay Low
- Division of Renal Medicine, Department of Medicine, Ng Teng Fong General Hospital, Singapore
| | - Wan-Ying Ng
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Neurology, Department of Medicine, National University Hospital, Singapore
| | - Horng-Ruey Chua
- Division of Nephrology, Department of Medicine, National University Hospital, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Patidar KR, Ma AT, Juanola A, Barone A, Incicco S, Kulkarni AV, Hernández JLP, Wentworth B, Asrani SK, Alessandria C, Abdelkader NA, Wong YJ, Xie Q, Pyrsopoulos NT, Kim SE, Fouad Y, Torre A, Cerda E, Ferrer JD, Maiwall R, Simonetto DA, Papp M, Orman ES, Perricone G, Solé C, Lange CM, Farias AQ, Pereira G, Gadano A, Caraceni P, Thevenot T, Verma N, Kim JH, Vorobioff JD, Cordova-Gallardo J, Ivashkin V, Roblero JP, Maan R, Toledo C, Gioia S, Fassio E, Marino M, Nabilou P, Vargas V, Merli M, Goncalves LL, Rabinowich L, Krag A, Balcar L, Montes P, Mattos AZ, Bruns T, Mohammed A, Laleman W, Carrera E, Cabrera MC, Girala M, Samant H, Raevens S, Madaleno J, Kim RW, Arab JP, Presa J, Ferreira CN, Galante A, Allegretti AS, Takkenberg B, Marciano S, Sarin SK, Durand F, Ginès P, Angeli P, Solà E, Piano S. Global epidemiology of acute kidney injury in hospitalised patients with decompensated cirrhosis: the International Club of Ascites GLOBAL AKI prospective, multicentre, cohort study. Lancet Gastroenterol Hepatol 2025; 10:418-430. [PMID: 40058397 DOI: 10.1016/s2468-1253(25)00006-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 01/03/2025] [Accepted: 01/06/2025] [Indexed: 04/14/2025]
Abstract
BACKGROUND Acute kidney injury (AKI) is a serious complication of cirrhosis. A systematic, global characterisation of AKI occurring in patients with cirrhosis is lacking. We therefore aimed to assess global differences in the characteristics, management, and outcomes of AKI in hospitalised patients with cirrhosis. METHODS In this prospective, multicentre, cohort study, we enrolled adults (≥18 years) with decompensated cirrhosis who were hospitalised for a cirrhosis-related complication, with or without AKI, at 65 centres across five continents. We captured AKI prevalence, stage, phenotype, and details on AKI management and clinical course. Universal health coverage index and gross national income per capita were also collected. The primary outcome was 28-day mortality. Multivariable models including demographic and clinical variables, cirrhosis cause, cirrhosis severity, AKI severity, AKI management variables, universal health coverage, and gross national income were used to analyse independent associations with 28-day mortality. Secondary outcomes were AKI classification, progression, and resolution. This study is complete and registered with ClinicalTrials.gov (NCT05387811). FINDINGS Between July 1, 2022, and May 31, 2023, we enrolled 3821 patients who were hospitalised for decompensated cirrhosis. Mean age was 57·7 years (SD 13·1), 2467 (64·6%) were men, and 1354 (35·4%) were women. Most patients were White (2128 [55·7%]). 1456 (38·1%, 95% CI 36·6-39·6) of 3821 patients had AKI (943 [64·8%] men and 513 [35·2%] women). Globally, patients presented with similar AKI stages, but patients from North America and Asia had the highest MELD-Na scores at presentation and the highest rates of peak AKI stage 3. Overall, hypovolaemic AKI was the most common phenotype (858 [58·9%] of 1456), followed by HRS-AKI (253 [17·4%]) and acute tubular necrosis (216 [14·8%]). The prevalences of hypovolaemic AKI and HRS-AKI were similar across regions, but acute tubular necrosis was more frequent in Asia (p<0·0001 across regions). Additionally, regional differences in the management of AKI (use of albumin, vasopressors, and diuretics) were found. 335 (28·6%) of 1171 patients with initial AKI stages 1 or 2 had progression to higher stages during hospitalisation. AKI resolved in 862 (59·2%) cases during hospitalisation. 333 (22·9%) patients with AKI had died by 28 days. Multivariable analyses showed that increased age, female sex, presence of ascites, presence of hepatic encephalopathy, increased white blood cell count, increased MELD-Na, hospital-acquired AKI, a lower universal health coverage index (<80), and not being in a high-income country were independently associated with an increased risk of 28-day mortality. Increased serum albumin was associated with a decreased risk of 28-day mortality. INTERPRETATION This study found important regional differences in AKI severity, phenotype, management, and outcomes in patients with decompensated cirrhosis. Health-care coverage remains an important driver of survival in patients with cirrhosis and AKI. FUNDING European Association Study for the Study of the Liver and the Italian Society of Internal Medicine.
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Affiliation(s)
- Kavish R Patidar
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Ann T Ma
- Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada
| | - Adrià Juanola
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas, Barcelona, Spain; School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Anna Barone
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
| | - Simone Incicco
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
| | | | - José Luis Pérez Hernández
- Department of Gastroenterology and Hepatology, Hospital General de México Dr Eduardo Liceaga, Mexico City, Mexico
| | - Brian Wentworth
- Division of Gastroenterology and Hepatology, University of Virginia School of Medicine, Charlottesville, VA, USA
| | | | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, University of Turin, Turin, Italy
| | | | - Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore; Duke-NUS Medical School, Singapore
| | - Qing Xie
- Department of Infectious Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Nikolaos T Pyrsopoulos
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Sung-Eun Kim
- Division of Gastroenterology and Hepatology, Hallym University College of Medicine, Chuncheon, South Korea
| | - Yasser Fouad
- Department of Gastroenterology, Hepatology and Endemic Medicine, Minia University, Minia, Egypt
| | - Aldo Torre
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Eira Cerda
- Central Military Hospital, Mexico City, Mexico
| | - Javier Diaz Ferrer
- Departamento del Aparato Digestivo, Hospital Edgardo Rebagliati-Clínica Internacional, Lima, Peru
| | - Rakhi Maiwall
- Institute of Liver and Biliary Sciences, New Delhi, India
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, NY, USA
| | - Maria Papp
- Division of Gastroenterology, Kalman Laki Doctoral School of Biomedical and Clinical Sciences, and Institute of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Eric S Orman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Giovanni Perricone
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Cristina Solé
- Gastroenterology and Hepatology Department, Parc Taulí University Hospital, Sabadell, Spain; Institut d'investigació i innovació Parc Taulí, Sabadell, Spain; CiberEHD, Madrid, Spain
| | - Christian M Lange
- Department of Medicine II, LMU University Hospital Munich, Munich, Germany
| | | | - Gustavo Pereira
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital, Rio de Janeiro, Brazil
| | - Adrian Gadano
- Liver Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Unit of Semeiotics, Liver and Alcohol-related diseases, IRCSS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Thierry Thevenot
- Department of Hepatology, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France
| | - Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Jeong Han Kim
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, South Korea
| | - Julio D Vorobioff
- Gastroenterology Department and Liver Unit, University of Rosario Medical School, Rosario, Argentina
| | | | - Vladimir Ivashkin
- Department of Internal Medicine, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Juan Pablo Roblero
- Departamento de Gastroenterología, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Raoel Maan
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, Netherlands
| | - Claudio Toledo
- Gastroenterology Unit, Universidad Australe de Chile, Valdivia, Chile
| | - Stefania Gioia
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Eduardo Fassio
- Gastroenterology Department and Liver Unit, Hospital Nacional Prof Alejandro Posadas, Buenos Aires, Argentina
| | - Monica Marino
- Liver Unit, Carlos Bonorino Udaondo Hospital, Buenos Aires, Argentina
| | - Puria Nabilou
- Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Victor Vargas
- Liver Unit, Hospital Vall d'Hebron, Universitat Autònoma, Barcelona, Spain
| | - Manuela Merli
- Department of Translational and Precision Medicine, Universita' degli Studi di Roma Sapienza, Roma, Italy
| | - Luciana Lofego Goncalves
- Serviço de Gastroenterologia, University Hospital-Federal University of Espirito Santo, Vitòria, Brazil
| | - Liane Rabinowich
- Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Department of Gastroenterology, Tel Aviv University, Tel Aviv, Israel
| | - Aleksander Krag
- Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Lorenz Balcar
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Pedro Montes
- Servicio de Gastroenterología, Hospital Nacional Daniel A Carrion, Bellavista, Peru
| | - Angelo Z Mattos
- Gastroenterology and Hepatology Unit, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Tony Bruns
- Medical Department III, University Hospital RWTH Aachen, Aachen, Germany
| | | | - Wim Laleman
- Department of Gastroenterology and Hepatology, Section of Liver and Biliopancreatic Disorders, University Hospitals Leuven, KU LEUVEN, Leuven, Belgium; Department of Medicine B (Gastroenterology, Hepatology, Endocrinology, Clinical Infectiology), University Hospital Muenster, Muenster, Germany
| | - Enrique Carrera
- Departamento de Gastroenterologia y Hepatologia, Hospital Eugenio Espejo, Universidad San Francisco de Quito, Quito, Ecuador
| | - María Cecilia Cabrera
- Gastroenterology Unit, Guillermo Almenara Hospital, Universidad Nacional Mayor de San Marcos, Lima, Peru
| | - Marcos Girala
- Departamento de Gastroenterología, Universidad Nacional de Asunciòn, Asunciòn, Paraguay
| | - Hrishikesh Samant
- Department of Hepatology, Ochsner Transplant Center, New Orleans, LA, USA
| | - Sarah Raevens
- Liver Research Centre Ghent, Ghent University Hospital, Ghent, Belgium
| | - Joao Madaleno
- Internal Medicine Department, Hospitais da Universidade de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal
| | - Ray W Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Juan Pablo Arab
- Department of Gastroenterology, Pontificia Universidad Católica de Chile, Santiago, Chile; Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - José Presa
- Liver Unit, Centro Hospitalar de Trásos-Montes e Alto Douro, Vila Real, Portugal
| | - Carlos Noronha Ferreira
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Unidade Local de Saúde Santa Maria, Lisbon, Portugal
| | - Antonio Galante
- Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Università della Svizzera Italiana, Lugano, Switzerland
| | | | - Bart Takkenberg
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, Netherlands
| | | | - Shiv K Sarin
- Institute of Liver and Biliary Sciences, New Delhi, India
| | - François Durand
- Hepatology and Liver Intensive Care, Beaujon Hospital, Clichy, France
| | - Pere Ginès
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
| | - Elsa Solà
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy.
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Mathis MR, Mentz GB, Cao J, Balczewski EA, Janda AM, Likosky DS, Schonberger RB, Hawkins RB, Heung M, Ailawadi G, Ladhania R, Sjoding MW, Kheterpal S, Singh K. Hospital and Clinician Practice Variation in Cardiac Surgery and Postoperative Acute Kidney Injury. JAMA Netw Open 2025; 8:e258342. [PMID: 40314957 PMCID: PMC12048843 DOI: 10.1001/jamanetworkopen.2025.8342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 02/27/2025] [Indexed: 05/03/2025] Open
Abstract
Importance Approximately 30% of US patients develop acute kidney injury (AKI) after cardiac surgery, which is associated with increased morbidity, mortality, and health care costs. The variation in potentially modifiable hospital- and clinician-level operating room practices and their implications for AKI have not been rigorously evaluated. Objective To quantify variation in clinician- and hospital-level hemodynamic and resuscitative practices during cardiac surgery and identify their associations with AKI. Design, Setting, and Participants This cohort study analyzed integrated hospital, clinician, and patient data extracted from the Multicenter Perioperative Outcomes Group dataset and the Society of Thoracic Surgeons Adult Cardiac Surgical Database. Participants were adult patients (aged ≥18 years) who underwent cardiac surgical procedures between January 1, 2014, and February 1, 2022, at 8 geographically diverse US hospitals. Patients were followed up through March 2, 2022. Statistical analyses were performed from October 2024 to February 2025. Exposures Hospital- and clinician-level variations in operating room hemodynamic practices (inotrope infusion >60 minutes and vasopressor infusion >60 minutes) and resuscitative practices (homologous red blood cell [RBC] transfusion and total fluid volume administration). Main Outcomes and Measures The primary outcome was consensus guideline-defined AKI (any stage) within 7 days after cardiac surgery. Hospital- and clinician-level variations were quantified using intraclass correlation coefficients (ICCs). Associations of hospital- and clinician-level practices with AKI were analyzed using multilevel mixed-effects models, adjusting for patient-level characteristics. Results Among 23 389 patients (mean [SD] age, 63 [13] years; 16 122 males [68.9%]), 4779 (20.4%) developed AKI after cardiac surgery. AKI rates varied across hospitals (median [IQR], 21.7% [15.5%-27.2%]) and clinicians (18.1% [10.1%-23.7%]). Significant clinician- and hospital-level variation existed for inotrope infusion (ICC, 6.2% [95% CI, 4.2%-8.0%] vs 17.9% [95% CI, 3.3%-31.9%]), vasopressor infusion (ICC, 11.7% [95% CI, 8.3%-14.9%] vs 44.5% [95% CI, 11.7%-63.5%]), RBC transfusion (ICC, 1.7% [95% CI, 0.9%-2.6%] vs 4.5% [95% CI, 1.2%-9.4%]), and fluid volume administration (ICC, 2.1% [95% CI, 1.3%-2.7%] vs 23.8% [95% CI, 2.7%-39.9%]). In multilevel risk-adjusted models, the AKI rate was higher for patients at hospitals with higher inotrope infusion rates (adjusted odds ratio [AOR], 1.98; 95% CI, 1.18-3.33; P = .01) and lower among clinicians with higher RBC transfusion rates (AOR, 0.89; 95% CI, 0.79-0.99; P = .03). Other practice variations were not associated with AKI. Conclusions and Relevance This cohort study of adult patients found that hospital- and clinician-level variation in operating room practices was associated with AKI after cardiac surgery, suggesting possible targets for intervention.
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Affiliation(s)
- Michael R. Mathis
- Department of Anesthesiology, University of Michigan Medical School, Ann Arbor
- Department of Computational Bioinformatics, University of Michigan Medical School, Ann Arbor
| | - Graciela B. Mentz
- Department of Anesthesiology, University of Michigan Medical School, Ann Arbor
| | - Jie Cao
- Joan and Irwin Jacobs Center for Health Innovation, University of California San Diego
| | - Emily A. Balczewski
- Department of Computational Bioinformatics, University of Michigan Medical School, Ann Arbor
| | - Allison M. Janda
- Department of Anesthesiology, University of Michigan Medical School, Ann Arbor
| | - Donald S. Likosky
- Department of Cardiac Surgery, University of Michigan Medical School, Ann Arbor
| | | | - Robert B. Hawkins
- Department of Cardiac Surgery, University of Michigan Medical School, Ann Arbor
| | - Michael Heung
- Nephrology Division, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor
| | - Gorav Ailawadi
- Department of Cardiac Surgery, University of Michigan Medical School, Ann Arbor
| | - Rahul Ladhania
- Department of Health Management and Policy, University of Michigan, Ann Arbor
- Department of Biostatistics, University of Michigan, Ann Arbor
| | - Michael W. Sjoding
- Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor
| | - Sachin Kheterpal
- Department of Anesthesiology, University of Michigan Medical School, Ann Arbor
| | - Karandeep Singh
- Joan and Irwin Jacobs Center for Health Innovation, University of California San Diego
- Division of Biomedical Informatics, Department of Medicine, University of California, San Diego
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Rabin B, D’Souza R, Weil EJ, Chang HH, Ebelt S, Scovronick N. Estimating the Association Between Outdoor Temperature and Acute Kidney Injury Using Alternative Case Definitions. J Occup Environ Med 2025; 67:e287-e293. [PMID: 39971751 PMCID: PMC12120693 DOI: 10.1097/jom.0000000000003333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
OBJECTIVE This study aimed to improve estimates of the association between acute kidney injury (AKI) and ambient heat exposure through better case ascertainment and by isolating community-acquired AKI. METHODS We conducted a case-crossover study using data on AKI-related emergency department (ED) visits in Atlanta. Daymet meteorology was used to assess exposure. We compared effect estimates for seven approaches (definitions) for identifying AKI. RESULTS There were between 5868 and 64,269 AKI cases depending on the definition. Higher temperatures were associated with AKI for all case definitions. Associations were strongest for cases with an ICD-coded AKI as a primary diagnosis (OR, 1.15; 95% CI, 1.01-1.31). We also observed significant ( P < 0.05) heat associations among cases identified using laboratory results but without an ICD-coded AKI diagnosis. CONCLUSIONS Many AKI cases are not diagnosed; these cases are associated with heat.
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Affiliation(s)
- Benjamin Rabin
- School of Medicine, Emory University, Atlanta, Georgia
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Rohan D’Souza
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA
| | - E. Jennifer Weil
- Department of Medicine, School of Medicine, Emory University, Atlanta, GA
| | - Howard H. Chang
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Stefanie Ebelt
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA
- Epidemiology, Editor
| | - Noah Scovronick
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA
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22
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Li N, Wang J, Zhou W, Li S, Yang L. External Validation of the Simple Postoperative Acute Kidney Injury Risk Index in Patients Admitted to the Intensive Care Unit After Noncardiac Surgery. Anesth Analg 2025; 140:1140-1148. [PMID: 39919018 DOI: 10.1213/ane.0000000000007320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Abstract
BACKGROUND The Simple Postoperative AKI Risk (SPARK) index is a novel model for predicting risk of postoperative acute kidney injury (PO-AKI) among patients after noncardiac surgery. However, the performance of the index has been inconsistent partly due to heterogeneity in case mix and effects of the involved clinical features. To clarify potential reasons for poor performance, we tested the SPARK index in a cohort of high-risk patients requiring intensive care unit (ICU) care after noncardiac surgery and examined whether model modification by refitting coefficients of clinical features could optimize model performance. METHODS This was a single-center prospective cohort study. Preoperative variables of the SPARK index were extracted from electronic medical records. PO-AKI was defined by an increase in sCr ≥26.5 mmol/L within 48 hours or 150% compared with the preoperative baseline value within 7 days after surgery, whereas critical AKI was defined as AKI stage 2 or greater and/or any AKI connected to postoperative death or requiring renal replacement therapy during the hospital stay. Discrimination was evaluated by the area under the receiver operating characteristic curve (AUC), and calibration was evaluated by the Hosmer-Lemeshow χ 2 test and calibration plot. Model modification was performed by rebuilding the model with the original variables of the SPARK index through proportional odds logistic regression among participants in the earlier study period and was validated in the later one. RESULTS A total of 973 patients were enrolled, among whom 79 (8.1%) PO-AKI cases and 14 (1.4%) critical AKI cases occurred. Our study participants demonstrated a higher SPARK risk score than the SPARK discovery cohort (eg, 8.02% vs 1.20% allocated in the highest risk group), and the incidence of both outcomes increased through the classes of the score (incidence proportion of PO-AKI increased from 2.56% in the lowest risk group to 25.64% in the highest risk group). The AUCs for PO-AKI and critical AKI were 0.703 (95% confidence interval [CI], 0.641-0.765) and 0.699 (95% CI, 0.550-0.848), respectively. The sensitivity, specificity, negative predictive value and positive predictive value were 68.35%, 57.49%, 95.36%, and 12.44%, respectively, when using 10% of predicted probability of PO-AKI as threshold. Calibration plots suggested acceptable consistency between the predicted and actual risk. After model modification, external validation demonstrated a significantly improved AUC for PO-AKI. CONCLUSIONS The SPARK index showed fair discrimination and calibration among patients admitted to the ICU after noncardiac surgery. Modification of the model improved the performance of the model in terms of predicting PO-AKI.
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Affiliation(s)
- Nan Li
- From the Department of Critical Care Medicine, Peking University First Hospital, Beijing, China
| | - Jinwei Wang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Weijie Zhou
- From the Department of Critical Care Medicine, Peking University First Hospital, Beijing, China
| | - Shuangling Li
- From the Department of Critical Care Medicine, Peking University First Hospital, Beijing, China
| | - Li Yang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
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Wu YJ, Yang YR, Yan YL, Yang HY, Du JR. Targeting mitochondrial dysfunction: an innovative strategy for treating renal fibrosis. Mol Cell Biochem 2025:10.1007/s11010-025-05297-w. [PMID: 40299265 DOI: 10.1007/s11010-025-05297-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Accepted: 04/23/2025] [Indexed: 04/30/2025]
Abstract
The incidence and hospitalization rate of kidney disease, especially end-stage renal disease, have increased significantly, which seriously endangers the health of patients. Mitochondria are the core organelles of cellular energy metabolism, and their dysfunction can lead to kidney energy supply insufficiency and oxidative stress damage, which has become a global public health problem. Studies have shown that the disturbance of mitochondrial quality control mechanisms, including mitochondrial dynamics, autophagy, oxidative stress regulation and biosynthesis, is closely related to the occurrence and development of renal fibrosis (RF). As a multicellular pathological process, RF involves the injury and shedding of podocytes, the transdifferentiation of renal tubular epithelial cells, the activation of fibroblasts, and the infiltration of macrophages, among which the mitochondrial dysfunction plays an important role. This review systematically elaborates the molecular mechanisms of mitochondrial damage during RF progression, aiming to provide theoretical foundations for developing novel therapeutic strategies to delay RF advancement.
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Affiliation(s)
- Yi-Jin Wu
- Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China
| | - Yan-Rong Yang
- Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China
| | - Ya-Ling Yan
- Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China
| | - Han-Yinan Yang
- Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China
| | - Jun-Rong Du
- Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
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Endre Z, Rebora P, Ostermann M. Persistent severe AKI is bad-where to go now? Intensive Care Med 2025:10.1007/s00134-025-07900-6. [PMID: 40298976 DOI: 10.1007/s00134-025-07900-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Accepted: 04/04/2025] [Indexed: 04/30/2025]
Affiliation(s)
- Zoltan Endre
- Department of Nephrology, School of Clinical Medicine, Faculty of Medicine & Health, Prince of Wales Hospital, UNSW Sydney, Sydney, Australia
| | - Paola Rebora
- Bicocca Bioinformatics Biostatistics and Bioimaging B4 Center, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- Fondazione IRCCS San Gerardo dei Tintori, Monza, MB, Italy
| | - Marlies Ostermann
- Department of Intensive Care, King's College London, Guy's & St Thomas' Hospital, London, UK.
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Jiang W, Zhang Y, Weng J, Song L, Liu S, Li X, Xu S, Shi K, Li L, Zhang C, Wang J, Yuan Q, Zhang Y, Shao J, Yu J, Zheng R. Explainable Machine Learning Model for Predicting Persistent Sepsis-Associated Acute Kidney Injury: Development and Validation Study. J Med Internet Res 2025; 27:e62932. [PMID: 40200699 PMCID: PMC12070005 DOI: 10.2196/62932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 03/10/2025] [Accepted: 04/07/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Persistent sepsis-associated acute kidney injury (SA-AKI) shows poor clinical outcomes and remains a therapeutic challenge for clinicians. Early identification and prediction of persistent SA-AKI are crucial. OBJECTIVE The aim of this study was to develop and validate an interpretable machine learning (ML) model that predicts persistent SA-AKI and to compare its diagnostic performance with that of C-C motif chemokine ligand 14 (CCL14) in a prospective cohort. METHODS The study used 4 retrospective cohorts and 1 prospective cohort for model derivation and validation. The derivation cohort used the MIMIC-IV database, which was randomly split into 2 parts (80% for model construction and 20% for internal validation). External validation was conducted using subsets of the MIMIC-III dataset and e-ICU dataset, and retrospective cohorts from the intensive care unit (ICU) of Northern Jiangsu People's Hospital. Prospective data from the same ICU were used for validation and comparison with urinary CCL14 biomarker measurements. Acute kidney injury (AKI) was defined based on serum creatinine and urine output, using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Routine clinical data within the first 24 hours of ICU admission were collected, and 8 ML algorithms were used to construct the prediction model. Multiple evaluation metrics, including area under the receiver operating characteristic curve (AUC), were used to compare predictive performance. Feature importance was ranked using Shapley Additive Explanations (SHAP), and the final model was explained accordingly. In addition, the model was developed into a web-based application using the Streamlit framework to facilitate its clinical application. RESULTS A total of 46,097 patients with sepsis from multiple cohorts were enrolled for analysis. Among 17,928 patients with sepsis in the derivation cohort, 8081 patients (45.1%) showed progression to persistent SA-AKI. Among the 8 ML models, the gradient boosting machine (GBM) model demonstrated superior discriminative ability. Following feature importance ranking, a final interpretable GBM model comprising 12 features (AKI stage, ΔCreatinine, urine output, furosemide dose, BMI, Sequential Organ Failure Assessment score, kidney replacement therapy, mechanical ventilation, lactate, blood urea nitrogen, prothrombin time, and age) was established. The final model accurately predicted the occurrence of persistent SA-AKI in both internal (AUC=0.870) and external validation cohorts (MIMIC-III subset: AUC=0.891; e-ICU dataset: AUC=0.932; Northern Jiangsu People's Hospital retrospective cohort: AUC=0.983). In the prospective cohort, the GBM model outperformed urinary CCL14 in predicting persistent SA-AKI (GBM AUC=0.852 vs CCL14 AUC=0.821). The model has been transformed into an online clinical tool to facilitate its application in clinical settings. CONCLUSIONS The interpretable GBM model was shown to successfully and accurately predict the occurrence of persistent SA-AKI, demonstrating good predictive ability in both internal and external validation cohorts. Furthermore, the model was demonstrated to outperform the biomarker CCL14 in prospective cohort validation.
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Affiliation(s)
- Wei Jiang
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Yaosheng Zhang
- School of Clinical and Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Jiayi Weng
- School of Economics and Management, Beijing Jiao Tong University, Beijing, China
| | - Lin Song
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Siqi Liu
- School of Economics and Management, Beijing Jiao Tong University, Beijing, China
| | - Xianghui Li
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Shiqi Xu
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Keran Shi
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Luanluan Li
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Chuanqing Zhang
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Jing Wang
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Quan Yuan
- School of Clinical and Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Yongwei Zhang
- School of Clinical and Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Jun Shao
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Jiangquan Yu
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Ruiqiang Zheng
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
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Qiao C, Zhou J, Wei C, Cao J, Zheng K, Lv M. Cardiac surgery-associated acute kidney injury: a decade of research trends and developments. Front Med (Lausanne) 2025; 12:1572338. [PMID: 40351461 PMCID: PMC12062005 DOI: 10.3389/fmed.2025.1572338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Accepted: 04/09/2025] [Indexed: 05/14/2025] Open
Abstract
Background Cardiac surgery-associated acute kidney injury (CSA-AKI) significantly increases postoperative mortality and healthcare costs. Despite the growing volume of CSA-AKI research, the field remains fragmented, with challenges in identifying high-impact studies, collaborative networks, and emerging trends. Bibliometric analysis addresses these gaps by systematically mapping knowledge structures, revealing research priorities, and guiding resource allocation for both researchers and clinicians. Method We analyzed 4,474 CSA-AKI-related publications (2014-2023) from the Web of Science Core Collection (WoSCC) using VOSviewer, CiteSpace, the Bibliometrix Package in R, and the bibliometric online analysis platform. Results Annual publications increased steadily, with the USA and China leading productivity. The Journal of Cardiothoracic and Vascular Anesthesia serves as the foremost preferred journal within this domain. Critical Care (IF = 15.1) has the highest impact factor. Yunjie Li published the most papers. John A Kellum has the highest H-index. The definition, pathogenesis or etiology, diagnosis, prediction, prevention and treatment, which are the research basis in CSA-AKI. Machine learning (ML) and prediction models emerged as dominant frontiers (2021-2023), reflecting a shift toward personalized risk stratification and real-time perioperative decision-making. These advancements align with clinical demands for early AKI detection and precision prevention. Conclusion This study not only maps the evolution of CSA-AKI research but also identifies priority areas for innovation: multicenter validation of predictive models to strengthen generalizability, preventive nephrology frameworks for long-term AKI survivor monitoring, and randomized controlled trials to confirm efficacy of machine learning-based CSA-AKI prediction tools.
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Affiliation(s)
- Changlong Qiao
- Department of Anesthesiology, Shandong Provincial Clinical Research Center for Anesthesiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Anesthesia and Respiratory Critical Medicine, Jinan, Shandong, China
| | - Jing Zhou
- Laboratory of Laparoscopic Technology, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Chuansong Wei
- Department of Anesthesiology, Shandong Provincial Clinical Research Center for Anesthesiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Anesthesia and Respiratory Critical Medicine, Jinan, Shandong, China
| | - Jing Cao
- Department of Anesthesiology, Shandong Provincial Clinical Research Center for Anesthesiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Anesthesia and Respiratory Critical Medicine, Jinan, Shandong, China
| | - Ke Zheng
- Graduate School, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Meng Lv
- Department of Anesthesiology, Shandong Provincial Hospital of Shandong First Medical University, Jinan, Shandong, China
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Chen JY, Pan HC, Wu VC. Association of Angiotensin Receptor-Neprilysin Inhibitors Use and Better Cardiorenal Outcomes in Patients With Heart Failure and Acute Kidney Disease. Cardiovasc Drugs Ther 2025:10.1007/s10557-025-07698-x. [PMID: 40266448 DOI: 10.1007/s10557-025-07698-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/08/2025] [Indexed: 04/24/2025]
Abstract
PURPOSE Angiotensin receptor-neprilysin inhibitors (ARNi) have been shown to improve cardiovascular outcomes in heart failure (HF) patients. However, their impact on HF patients with concurrent acute kidney disease (AKD) remains underexplored. This study investigated the outcomes of ARNi compared to angiotensin-converting enzyme inhibitors (ACEi) in HF patients with AKD. METHODS The study included 20,009 hospitalized HF and AKD patients who underwent dialysis during hospitalization, recovered from dialysis within 90 days after discharge, and were followed until November 30, 2022, using data from TriNetX. The study period began in July 2015, coinciding with the availability of ARNi in the market. Propensity score matching (1:1) was applied to balance ARNi and ACEi groups. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were calculated to assess the risks of mortality, major adverse kidney events (MAKE), readmission and major adverse cardiac events (MACE). The follow-up period was conducted with a maximum duration of 5 years. RESULTS A total of 20,009 AKD patients (mean [SD] age, 59.1 [12.2] years) were enrolled, of whom 21.9% received ARNi, with a median follow-up of 2.3 years. After matching, 4391 patients (mean age, 58.6 years; male, 67.9%) were identified in both the ARNi and control groups. ARNi users exhibited a significantly lower risk of mortality (aHR, 0.32, 95% CI 0.13-0.80, p = 0.01), MAKE (aHR, 0.58, 95% CI 0.51-0.66, p < 0.01 ), and readmission (aHR, 0.61, 95% CI 0.55-0.68, p <0.01) versus controls. However, no significant difference in the risk of MACE was observed between the two groups (aHR, 0.94, 95% CI 0.82-1.09, p = 0.78). Subgroup analysis revealed ARNi users, when concomitantly treated with mineralocorticoids, diuretics, or beta-blockers had significantly lower risks of mortality, readmission, and MAKE than the control group. In addition, ARNi significantly reduced mortality and MAKE in patients with GFR 30-60 mL/min/1.73 m2, irrespective of proteinuria status. However, no significant benefit was observed in patients with GFR <30 mL/min/1.73 m2. CONCLUSIONS In HF patients with AKD, ARNi was associated with reduced all-cause mortality, MAKE, and readmission risks compared to ACEi, particularly with concurrent mineralocorticoids, diuretics, or beta-blockers. Future research is necessary to further investigate the impact of ARNi on outcomes in patients with HF and AKD.
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Affiliation(s)
- Jui-Yi Chen
- Division of Nephrology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
- Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Heng-Chih Pan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Vin-Cent Wu
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- NSARF (National Taiwan University Hospital Study Group of ARF) and TAIPAI, (Taiwan Primary Aldosteronism Investigators), Taipei, Taiwan.
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Casas-Aparicio G, Caballero-Islas AE, León-Ortiz A, Escamilla-Illescas D, Rueda-Escobedo Y, Ascención-López C, Hernández-Quino D, Flores-Vargas A, Sosa-Chombo J, Tolentino-de La Mora A, Saucedo-Pruneda A, Piten-Isidro E. Early Driving Pressure Is Associated with Major Adverse Kidney Events at 30 Days in ARDS Patients with SARS-CoV-2. J Clin Med 2025; 14:2783. [PMID: 40283616 PMCID: PMC12027899 DOI: 10.3390/jcm14082783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 04/05/2025] [Accepted: 04/11/2025] [Indexed: 04/29/2025] Open
Abstract
Background: Major adverse kidney events (MAKEs), including death, persistent AKI (pAKI), and renal replacement therapy, are more common in SARS-CoV-2-related ARDS. Invasive mechanical ventilation (IMV), systemic inflammation, and hemodynamic changes drive this risk. This study examines early IMV settings and urinary kidney biomarkers (UKBs) to better understand the development of MAKEs at 30 days. Methods: This prospective, cross-sectional cohort study was conducted in a single center between September and October 2021. This study included adults (≥18 years) diagnosed with ARDS due to SARS-CoV-2, requiring IMV within the first 6 h of admission. Exclusion criteria included a history of chronic kidney disease (CKD) and pregnant women. Initial mechanical ventilator settings were recorded after compliance-guided PEEP titration, and urine samples were collected for the analysis of UKBs at the same time. Our primary and secondary endpoints were to assess risk factors associated with MAKEs at 30 days and pAKI, respectively. Results: The cohort included 45 patients, with a median age of 57.75 (±18.64) years. In total, 32 (71%) developed MAKEs and 22 (48.8%) developed pAKI. MAKEs were associated with older age (adjusted odds ratio (aORs) = 1.23 95% CI: 1.00-1.22; p = 0.038) and higher driving pressure (ΔP) (aORs = 1.62, 95% CI:1.01-2.60, p = 0.043). Only urinary neutrophil gelatinase-associated lipocalin (uNGal) > 40 ng/mL was associated with pAKI (aORs = 8.54, 95% CI:1.75-41.65, p = 0.008). Conclusions: Early ventilator settings, particularly higher ΔP, play a critical role in the development of MAKEs. uN-Gal could enhance the early detection of pAKI, providing opportunities for timely interventions.
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Affiliation(s)
- Gustavo Casas-Aparicio
- Coordinación de Nefrología, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México 14080, Mexico; (A.E.C.-I.); (A.L.-O.)
- Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México 14080, Mexico;
| | - Adrián E. Caballero-Islas
- Coordinación de Nefrología, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México 14080, Mexico; (A.E.C.-I.); (A.L.-O.)
| | - Antonio León-Ortiz
- Coordinación de Nefrología, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México 14080, Mexico; (A.E.C.-I.); (A.L.-O.)
| | - David Escamilla-Illescas
- Dirección de Medicina, Fundación Clínica Médica Sur. Puente de Piedra 29, Col. Toriello Guerra, Ciudad de México 14040, Mexico;
| | - Yovanna Rueda-Escobedo
- Departamento de Enseñanza, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col. Sección XVI, Ciudad de Mexico 14080, Mexico;
| | - Carlos Ascención-López
- Facultad de Medicina Benemérita Universidad Autónoma de Puebla, Heroica Puebla de Zaragoza 72420, Mexico; (C.A.-L.); (D.H.-Q.)
| | - Diana Hernández-Quino
- Facultad de Medicina Benemérita Universidad Autónoma de Puebla, Heroica Puebla de Zaragoza 72420, Mexico; (C.A.-L.); (D.H.-Q.)
| | - Aimee Flores-Vargas
- Médico Adscrito a la Subdirección de Atención Médica de Neumología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col. Sección XVI, Ciudad de Mexico 14080, Mexico; (A.F.-V.); (J.S.-C.); (A.S.-P.)
| | - Jesús Sosa-Chombo
- Médico Adscrito a la Subdirección de Atención Médica de Neumología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col. Sección XVI, Ciudad de Mexico 14080, Mexico; (A.F.-V.); (J.S.-C.); (A.S.-P.)
| | - Abraham Tolentino-de La Mora
- Departamento de Investigación en Tabaquismo y EPOC, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col. Sección XVI, Ciudad de México 14080, Mexico;
| | - Ana Saucedo-Pruneda
- Médico Adscrito a la Subdirección de Atención Médica de Neumología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Col. Sección XVI, Ciudad de Mexico 14080, Mexico; (A.F.-V.); (J.S.-C.); (A.S.-P.)
| | - Elvira Piten-Isidro
- Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México 14080, Mexico;
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Peng X, Cai Y, Huang H, Fu H, Wu W, Hong L. A Predictive Model for Acute Kidney Injury Based on Leukocyte-Related Indicators in Hepatocellular Carcinoma Patients Admitted to the Intensive Care Unit. Mediators Inflamm 2025; 2025:7110012. [PMID: 40270515 PMCID: PMC12017962 DOI: 10.1155/mi/7110012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 03/06/2025] [Indexed: 04/25/2025] Open
Abstract
Background: This study aimed to develop and validate a straightforward clinical risk model utilizing white blood cell (WBC) counts to predict acute kidney injury (AKI) in critically sick patients with hepatocellular carcinoma (HCC). Methods: Data were taken from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database for the training cohort. Data for an internal validation cohort were obtained from the eICU Collaborative Research Database (eICU-CRD), while patients from our hospital were utilized for external validation. A risk model was created utilizing significant indicators identified through multivariate logistic regression, following logistic regression analysis to determine the primary predictors of WBC-related biomarkers for AKI prediction. The Kaplan-Meier curve was employed to evaluate the prognostic efficacy of the new risk model. Results: A total of 1628 critically sick HCC patients were enrolled. Among these, 23 (23.2%) patients at our hospital, 84 (17.9%) patients in the eICU-CRD database, and 379 (35.8%) patients in the MIMIC-IV database developed AKI. A unique risk model was developed based on leukocyte-related indicators following the multivariate logistic regression analysis, incorporating white blood cell to neutrophil ratio (WNR), white blood cell to monocyte ratio (WMR), white blood cell to hemoglobin ratio (WHR), and platelet to lymphocyte ratio (PLR). This risk model exhibited robust predictive capability for AKI, in-hospital mortality, and ICU mortality across the training set, internal validation set, and external validation set. Conclusion: This risk model seems to have practical consequences as an innovative and accessible tool for forecasting the prognosis of critically ill HCC patients, which may, to some degree, aid in identifying equitable risk assessments and treatment strategies.
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Affiliation(s)
- Xiulan Peng
- Department of Oncology, The Second Affiliated Hospital of Jianghan University, Wuhan 430050, Hubei Province, China
| | - Yahong Cai
- Department of Oncology, The Second Affiliated Hospital of Jianghan University, Wuhan 430050, Hubei Province, China
| | - Huan Huang
- Department of Oncology, Suizhou Zengdu Hospital, Suizhou 441300, Hubei, China
| | - Haifeng Fu
- Department of Hepatopancreatobiliary Surgery, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan 442008, Hubei, China
| | - Wei Wu
- Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430000, Hubei Province, China
| | - Lifeng Hong
- Department of Cardiology, The Second Affiliated Hospital of Jianghan University, Wuhan 430050, Hubei Province, China
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dos Reis AA, Duarte TTDP, Ipolito MZ, da Silva KGN, Magro PPM, da Silva Magro MC. Impact of prognostic scores on acute kidney injury assessment in the postoperative period of myocardial revascularization. Rev Esc Enferm USP 2025; 59:e20240410. [PMID: 40233209 PMCID: PMC11999537 DOI: 10.1590/1980-220x-reeusp-2024-0410en] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 02/06/2025] [Indexed: 04/17/2025] Open
Abstract
OBJECTIVE To determine the impact of the Simplified Acute Physiology Score 3 and the Sequential Organ Failure Assessment in assessing the severity of acute kidney injury in patients after cardiopulmonary bypass. METHOD A retrospective cohort study with a non-probabilistic sample. Inferential analysis was performed using Pearson's chi-square, Fisher's exact and Mann-Whitney tests, with a significance level of 5%. RESULTS The prevalence of acute kidney injury was 31.4%. The Simplified Acute Physiology Score 3 and the Sequential Organ Failure Assessment showed higher scores in patients with kidney injury (58 (48-64) versus 48 (37-57), p = 0.02; 7 (6-9) versus 6 (5-7), p = 0.003), in addition to a longer stay in intensive care, 8 (6-16) versus 6 (5-8) (p = 0.02) days, respectively. CONCLUSION Patients with acute kidney injury remained in intensive care longer, and the Simplified Acute Physiology Score 3 and the Sequential Organ Failure Assessment showed good performance, evidencing greater severity among patients with acute kidney injury in the postoperative period of coronary artery bypass grafting.
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Affiliation(s)
- Abraão Alves dos Reis
- Universidade de Brasília, Faculdade de Ciências e Tecnologias em Saúde, Brasília, DF, Brazil
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La Via L, Cuttone G, Sinatra N, Abrignani MG, Geraci G, Ippati G, Rubulotta FM. The Furosemide Stress Test: A Dynamic Tool for Predicting Acute Kidney Injury Progression in Critical Care Medicine. J Clin Med 2025; 14:2595. [PMID: 40283425 PMCID: PMC12028265 DOI: 10.3390/jcm14082595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2025] [Revised: 03/25/2025] [Accepted: 04/04/2025] [Indexed: 04/29/2025] Open
Abstract
Acute kidney injury (AKI) remains a significant challenge in critical care medicine, affecting up to 50% of intensive care unit patients with substantial mortality rates. While traditional approaches to AKI assessment rely on static measurements like serum creatinine and urine output, the furosemide stress test (FST) has emerged as a dynamic functional tool for evaluating renal tubular function and predicting AKI progression. This comprehensive review examines the historical development, physiological basis, technical aspects, and clinical applications of FST in various patient populations. Originally developed and validated in 2013, FST has demonstrated superior predictive capabilities for AKI progression and the need for renal replacement therapy compared to conventional biomarkers. The test's mechanism relies on assessing the kidney's response to a standardized furosemide challenge, providing insights into both the structural integrity and functional reserve of the renal tubular system. Standardized protocols have been established for different clinical scenarios, though implementation challenges remain, including timing considerations, patient selection, and resource requirements. FST has shown utility in critical care, post-cardiac surgery, sepsis-associated AKI, and heart failure settings. Recent developments include integration with artificial intelligence, personalized medicine approaches, and combination with novel biomarkers. While limitations exist, including contraindications and technical challenges, ongoing research continues to refine protocols and expand applications. This review highlights FST's role as a valuable prognostic tool in modern AKI management and discusses future directions, including automated monitoring systems, protocol standardization efforts, and potential applications in different patient populations.
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Affiliation(s)
- Luigi La Via
- Department of Anesthesia and Intensive Care 1, University Hospital Policlinico “G. Rodolico–San Marco”, 95123 Catania, Italy;
| | - Giuseppe Cuttone
- Trauma Center Unit, “Villa Sofia-Cervello” Hospital, 90146 Palermo, Italy;
| | - Nicola Sinatra
- Nephrology and Dialysis Unit, “Paolo Borsellino” Hospital, 91025 Marsala, Italy;
| | | | - Giulio Geraci
- Faculty of Medicine and Surgery, Kore University, 94100 Enna, Italy;
| | - Giovanni Ippati
- Department of Anesthesia and Intensive Care, “S.A. Abate” Hospital, 91016 Erice, Italy;
| | - Francesca Maria Rubulotta
- Department of Anesthesia and Intensive Care 1, University Hospital Policlinico “G. Rodolico–San Marco”, 95123 Catania, Italy;
- Department of General Surgery and Medical Surgical Specialties, University of Catania, 95124 Catania, Italy
- The International Women in Intensive and Critical Care Network IWIN Foundation, 94011 Sicily, Italy
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Mauroner L, Kellum JA, Levey AS, Formeck C, Fuhrman DY. The Incidence and Outcomes of Acute Kidney Disease in Critically Ill Children. KIDNEY360 2025; 6:543-549. [PMID: 39786980 PMCID: PMC12045505 DOI: 10.34067/kid.0000000693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 01/06/2025] [Indexed: 01/12/2025]
Abstract
Key Points Major adverse kidney events are common in children who develop acute kidney disease in the intensive care unit. Acute kidney disease criteria identify critically ill children at risk for major adverse kidney event who do not meet AKI or CKD criteria. Background Acute kidney disease (AKD) includes abnormalities of kidney function present for <90 days. AKI is defined as a subset of AKD with onset within 7 days. There are scant data on the rates of AKD in children and its association with outcomes. Our primary objective was to examine the rates of AKD with and without AKI and compare major adverse events in children in the pediatric intensive care unit (PICU). Methods This is a retrospective cohort study of patients aged 18 years or younger who were admitted to a quaternary care PICU between 2009 and 2016 using the high-density pediatric database. All patients included in the primary analysis had a known baseline serum creatinine. Patients who had a baseline eGFR <60 ml/min per 1.73 m2 or a history of dialysis dependence or kidney transplant were excluded. AKI and AKD were defined by Kidney Disease Improving Global Outcomes definitions. Major adverse kidney events at 90 days (MAKE-90) was defined as a composite outcome of death, dialysis, or persistent kidney dysfunction 90 days after PICU admission. Results Among 5922 children included in this study, 1199 (20.2%) had AKD, of which 1092 (91%) had AKD with AKI and 107 (8.9%) had AKD without AKI. MAKE-90 occurred in 26% (308/1199) of those with AKD compared with 3.6% (172/4723) without (P ≤ 0.001). MAKE-90 occurred in 26% (279/1092) of AKD with AKI and 27% (29/107) of AKD without AKI. After adjusting for age, sex, and illness severity, compared with patients who had no AKD, patients with AKD with AKI (adjusted odds ratio, 14.39; 95% confidence interval, 11.06 to 18.72), and patients with AKD without AKI (adjusted odds ratio, 7.83; 95% confidence interval, 4.54 to 13.51) had a greater odds of MAKE-90. Conclusions More than a quarter of pediatric critically ill patients with AKD develop MAKE-90. Even in the absence of AKI, AKD is an independent risk factor for MAKE-90.
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Affiliation(s)
- Lillian Mauroner
- Division of Nephrology, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
| | - John A. Kellum
- Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Andrew S. Levey
- Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts
| | - Cassandra Formeck
- Division of Nephrology, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
- Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Dana Y. Fuhrman
- Division of Nephrology, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
- Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Division of Pediatric Critical Care Medicine, Department of Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
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Wang X, Li C, Xu L, Jiang S, Guan C, Che L, Wang Y, Man X, Xu Y. Construction and validation of prognostic models for acute kidney disease and mortality in patients at risk of malnutrition: an interpretable machine learning approach. Clin Kidney J 2025; 18:sfaf080. [PMID: 40236512 PMCID: PMC11997651 DOI: 10.1093/ckj/sfaf080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Indexed: 04/17/2025] Open
Abstract
Background Acute kidney injury (AKI) is a prevalent complication in patients at risk of malnutrition, elevating the risks of acute kidney disease (AKD) and mortality. AKD reflects the adverse events developing after AKI. This study aimed to develop and validate machine learning (ML) models for predicting the occurrence of AKD, AKI and mortality in patients at risk of malnutrition. Methods We retrospectively reviewed the medical records of patients at risk of malnutrition. Eight ML algorithms were employed to predict AKD, AKI and mortality. The performance of the best model was evaluated using various metrics and interpreted using the SHapley Additive exPlanation (SHAP) method. An artificial intelligence (AI)-driven web application was also created based on the best model. Results A total of 13 395 patients were included in our study. Among them, 1751 (13.07%) developed subacute AKD, 1253 (9.35%) were transient AKI, and 1455 (10.86%) met both AKI and AKD criteria. The incidence rate of mortality was 6.74%. The light gradient boosting machine (LGBM) outperformed other models in predicting AKD, AKI and mortality, with area under curve values of 0.763, 0.801 and 0.881, respectively. The SHAP method revealed that AKI stage, lactate dehydrogenase, albumin, aspirin usage and serum creatinine were the top five predictors of AKD. An online prediction website for AKI, AKD and mortality was developed based on the final models. Conclusions The LGBM models provide an effective method for predicting AKD, AKI and mortality at an early stage in patients at risk of malnutrition, enabling prompt interventions. Compared with the AKD model, the models for predicting AKI and mortality perform better. The AI-driven web application can significantly aid in creating personalized preventive measures. Future work will aim to expand the application to larger, more diverse populations, incorporate additional biomarkers and refine ML algorithms to improve predictive accuracy and clinical utility.
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Affiliation(s)
- Xinyuan Wang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chenyu Li
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lingyu Xu
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Siqi Jiang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chen Guan
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lin Che
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yanfei Wang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaofei Man
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yan Xu
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
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Suksamai A, Khaoprasert S, Chaiprasert A, Chirapongsathorn S. Urine TIMP2.IGFBP7 Reflects Kidney Injury After Moderate Volume Paracentesis in Patients With Ascites: A Randomized Control Study. JGH Open 2025; 9:e70168. [PMID: 40264987 PMCID: PMC12012385 DOI: 10.1002/jgh3.70168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 04/01/2025] [Accepted: 04/12/2025] [Indexed: 04/24/2025]
Abstract
Background Urinary biomarkers may predict acute kidney injury (AKI) in cirrhosis with ascites in a moderate volume paracentesis setting. Objective The study aimed to assess the risk and consequence of AKI and its progression in patients with decompensated cirrhosis undergoing paracentesis using a urine test measuring tissue inhibitor of metalloproteinases-2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7). Methods A randomized, controlled trial was performed. All outpatients with decompensated cirrhosis with ascites and diuretic complications were enrolled and randomized into 3 and 5 L paracentesis groups. Serial urine samples were analyzed for TIMP2. IGFBP7 concentration before and after paracentesis. Results A total of 90 patients with decompensated cirrhosis were consecutively enrolled during the study period. After screening, 29 patients were enrolled in the 3-L paracentesis group, and 25 patients were enrolled in the 5-L paracentesis group. The mean of the MELD score was 8 ± 1.2. Urine TIMP2.IGFBP7 > 2, rising urine TIMP2, and rising urine TIMP2/urine Cr were shown in patients within the 5-L group for 48% (p = 0.015), 32% (p = 0.049), and 76% (p = 0.010) respectively, indicating a higher incidence of renal tubular injury markers in this group. Urine TIMP2.IGFBP7/1000 > 2 was statistically significant to predict a hemodynamic event (p = 0.002). Conclusion In cirrhotic patients with ascites undergoing paracentesis, a 5-L paracentesis volume was associated with a higher incidence of renal tubular injury markers. Trail Registration: The national clinical registration number was TCTR20191116003.
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Affiliation(s)
- Anuchit Suksamai
- Division of Gastroenterology and Hepatology, Department of MedicinePhramongkutklao Hospital and College of MedicineBangkokThailand
| | - Sanpolpai Khaoprasert
- Division of Gastroenterology and Hepatology, Department of MedicinePhramongkutklao Hospital and College of MedicineBangkokThailand
| | - Amnart Chaiprasert
- Division of Nephrology, Department of MedicinePhramongkutklao Hospital and College of MedicineBangkokThailand
| | - Sakkarin Chirapongsathorn
- Division of Gastroenterology and Hepatology, Department of MedicinePhramongkutklao Hospital and College of MedicineBangkokThailand
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Patidar KR, Tu W, Cotter TG, Simonetto DA, Asgharpour A, Jan MY, Tang Q, Yu Y, Li Y, Taiwo M, Nagesh PT, Dasarathy S, Kamath PS, McClain CJ, Chalasani N, Szabo G, Bataller R, Mitchell M, Mehal WZ, Nagy LE, Shah VH, Gawrieh S, Sanyal AJ. Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone. Hepatology 2025; 81:1256-1268. [PMID: 39028887 PMCID: PMC11829732 DOI: 10.1097/hep.0000000000001019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 06/25/2024] [Indexed: 07/21/2024]
Abstract
BACKGROUND AND AIMS In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial. APPROACH AND RESULTS Data from 147 participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed. AKI, AKI phenotypes, and kidney injury biomarkers were compared between participants who did/did not develop AKI in the 2 treatment arms. Multivariable competing risk analyses were performed to identify baseline risk factors for incident AKI, with death treated as a competing event. Risk factors considered were age, sex, mean arterial pressure, white blood cell count, albumin, MELD, ascites, HE, and treatment arm. At baseline, no participants had AKI; 33% (n=49) developed AKI during follow-up. AKI incidence was higher in A+Z than in PRED (45% [n=33] versus 22% [n=16], p =0.001). AKI phenotypes were similar between the 2 treatment arms ( p =0.361), but peak AKI severity was greater in A+Z than PRED (stage 3 n=21 [63.6%] vs. n=8 [50.0%], p =0.035). At baseline, urine-neutrophil-gelatinase-associated lipocalin levels were similar between participants who developed AKI in both treatment arms ( p =0.319). However, day 7 and 14 urine-neutrophil-gelatinase-associated lipocalin levels were significantly elevated in participants treated with A+Z who developed AKI versus participants treated with PRED who developed AKI ( p =0.002 and 0.032, respectively). On multivariable competing risk analysis, only A+Z was independently associated with incident AKI (subdistribution hazard ratio 2.35, p =0.005). CONCLUSIONS AKI occurred more frequently and was more severe in participants treated with A+Z. A+Z-treated participants with AKI had higher urine-neutrophil-gelatinase-associated lipocalin, suggesting that A+Z maybe nephrotoxic in patients with severe alcohol-associated hepatitis.
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Affiliation(s)
- Kavish R. Patidar
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Indiana University, Indianapolis, Indiana, USA
- Department of Internal Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Wanzhu Tu
- Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, Indiana, USA
| | - Thomas G. Cotter
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Douglas A. Simonetto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Amon Asgharpour
- Division of Gastroenterology, Department of Internal Medicine, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Muhammad Y. Jan
- Division of Nephrology, Department of Internal Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Qing Tang
- Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, Indiana, USA
| | - Yunpeng Yu
- Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, Indiana, USA
| | - Yang Li
- Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, Indiana, USA
| | - Moyinoluwa Taiwo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Prashanth Thevkar Nagesh
- Division of Gastroenterology, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Srinivasan Dasarathy
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Patrick S. Kamath
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Craig J. McClain
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Louisville, Louisville, Kentucky, USA
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Gyongyi Szabo
- Division of Gastroenterology, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Ramon Bataller
- Division of Gastroenterology and Hepatology and Nutrition, Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
- School of Medicine and Health Sciences, Liver Unit, Hospital Clinic, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Mack Mitchell
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Wajahat Z. Mehal
- Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut, USA
- Department of Internal Medicine, Veterans Affairs Medical Center, West Haven, Connecticut, USA
| | - Laura E. Nagy
- Department of Inflammation and Immunity, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Vijay H. Shah
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Samer Gawrieh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Arun J. Sanyal
- Division of Gastroenterology, Department of Internal Medicine, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
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Wigmore GJ, Deane AM, Presneill JJ, Serpa Neto A, Eastwood G, Maiden MJ, Bihari S, Baker RA, Bennetts JS, Ghanpur R, Anstey JR, Raman J, Bellomo R. The Renal Effect of 20% Human Albumin Solution Fluid Bolus Therapy in Patients After Cardiac Surgery. A Secondary Analysis of the HAS FLAIR II Randomized Clinical Trial. J Cardiothorac Vasc Anesth 2025; 39:967-974. [PMID: 39837683 DOI: 10.1053/j.jvca.2024.12.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 12/01/2024] [Accepted: 12/29/2024] [Indexed: 01/23/2025]
Abstract
OBJECTIVE To compare the effects of fluid bolus therapy (FBT) with 20% albumin to crystalloid FBT on the incidence of cardiac surgery-associated acute kidney injury (CSA-AKI) and its severity and duration. DESIGN Secondary analysis of the multicenter, parallel-group, open-label, randomized HAS FLAIR-II trial. SETTING Six intensive care units. PARTICIPANTS Patients who required clinician-determined FBT after cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS Patients were randomized to receive FBT with 20% albumin (up to 400 mL/day) or crystalloid fluid for all FBTs in the intensive care unit. MEASUREMENTS AND MAIN RESULTS A total of 452 patients were included in the modified intention-to-treat population (224 in the 20% albumin group and 228 in the crystalloid group). AKI occurred in 54 (24%) patients in the 20% albumin group and 50 (22%) in the crystalloid group (odds ratio: 1.13, 95% confidence interval [CI]: 0.73 to 1.76). However, in patients who developed stages 2 and 3 AKI, those allocated to 20% albumin had a significantly lower median time-weighted average (TWA) creatinine: 144 µmol/L (interquartile range [IQR]: 109 to 162) versus 254 µmol/L (IQR: 182 to 294) than the crystalloid group (difference -105 µmol/L, [95% CI -170 to -41], p = 0.003) and a lower peak serum creatinine (-110 µmol/L [-189 to -32], p = 0.01). The reduced TWA creatinine in the 20% albumin group was seen in patients with both a low (p = 0.04) and normal preoperative serum albumin concentration (p < 0.001). CONCLUSIONS FBT with 20% albumin compared with crystalloid-based regimen did not reduce the occurrence of AKI in patients after cardiac surgery. However, it reduced the severity and duration of stages 2 and 3 AKI.
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Affiliation(s)
- Geoffrey J Wigmore
- Department of Critical Care, Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia; Department of Anaesthesia and Pain Medicine, Western Health, Melbourne, Victoria, Australia.
| | - Adam M Deane
- Department of Critical Care, Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia; Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Jeffrey J Presneill
- Department of Critical Care, Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia; Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia; Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Ary Serpa Neto
- Department of Critical Care, Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia; Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia; Department of Critical Care Medicine, Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Glenn Eastwood
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
| | - Matthew J Maiden
- Department of Critical Care, Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia; Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia; Intensive Care Unit, Barwon Health, Geelong, Victoria, Australia
| | - Shailesh Bihari
- College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia; Department of ICCU, Flinders Medical Centre, Bedford Park, South Australia, Australia
| | - Robert A Baker
- Cardiothoracic Quality and Outcomes, Flinders Medical Centre and College of Medicine and Public Health Flinders University, South Australia, Australia
| | - Jayme S Bennetts
- Cardiothoracic Quality and Outcomes, Flinders Medical Centre and College of Medicine and Public Health Flinders University, South Australia, Australia
| | - Rashmi Ghanpur
- Department of Intensive Care, Warringal Private Hospital, Melbourne, Australia
| | - James R Anstey
- Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Jaishankar Raman
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia; University of Melbourne, Parkville, Victoria, Australia; St Vincent's Hospital, Melbourne, Victoria, Australia; Department of Cardiothoracic Surgery, Townsville University Hospital, Townsville, Queensland, Australia
| | - Rinaldo Bellomo
- Department of Critical Care, Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia; Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia; Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia; Data Analytics Research and Evaluation Centre, Austin Hospital, Melbourne, Victoria, Australia
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Nakanishi M, Mizuno T, Sakai S, Hira D, Koseki T, Matsubara T, Yokoi H, Yanagita M, Terada T, Yamada S, Tsuboi N. Frequency of Acute Kidney Injury After the Initiation of Vitamin D Receptor Activators: A Multicenter Retrospective Observational Study. Clin Drug Investig 2025; 45:191-199. [PMID: 40074969 DOI: 10.1007/s40261-025-01429-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/25/2025] [Indexed: 03/14/2025]
Abstract
BACKGROUND AND OBJECTIVES Vitamin D receptor activators (VDRAs) are widely used in patients with osteoporosis; however, the frequency of acute kidney injury (AKI) due to VDRAs is unclear. This study aimed to investigate whether the incidence of AKI after VDRA initiation differed among patients with different renal functions. METHODS The medical records of Japanese patients who were newly prescribed with VDRAs for osteoporosis at the Fujita Health University Hospital or Kyoto University Hospital between April 2012 and March 2022 were retrospectively reviewed in this study. The RIFLE (Risk, Injury, Failure, Loss of function, End-stage kidney disease) criteria were used to assess the incidence of AKI within 7 days after initiation of VDRA therapy. Additionally, the AKI algorithm was used to assess the incidence of AKI from 8 to 365 days after initiation of VDRA therapy. RESULTS The incidence of AKI, as defined by the RIFLE criteria, was significantly higher in patients with normal renal function or end-stage renal failure than in those with mild renal decline (p < 0.05); the incidence of AKI, defined using the AKI algorithm, showed a similar trend. We found that the lack of serum calcium level monitoring before the initiation of VDRAs might be a risk factor for AKI defined by the RIFLE criteria (odds ratio = 2.004, p = 0.096). CONCLUSIONS The incidence of AKI after the initiation of VDRA therapy was high, even if renal function was normal. Thus, our results suggest that monitoring serum calcium levels before the initiation of VDRA therapy is necessary, regardless of renal function.
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Affiliation(s)
- Masanori Nakanishi
- Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine, Kutsukakecho Dengakugakubo 1-98, Toyoake, Aichi, 470-1101, Japan
| | - Tomohiro Mizuno
- Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine, Kutsukakecho Dengakugakubo 1-98, Toyoake, Aichi, 470-1101, Japan.
| | - Shinya Sakai
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, Japan
| | - Daiki Hira
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, Japan
| | - Takenao Koseki
- Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine, Kutsukakecho Dengakugakubo 1-98, Toyoake, Aichi, 470-1101, Japan
| | - Takeshi Matsubara
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hideki Yokoi
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Motoko Yanagita
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tomohiro Terada
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, Japan
| | - Shigeki Yamada
- Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine, Kutsukakecho Dengakugakubo 1-98, Toyoake, Aichi, 470-1101, Japan
| | - Naotake Tsuboi
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
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Shao B, Wang HD, Ren SH, Chen Q, Wang ZB, Xu YN, Liu T, Sun CL, Xiao YY, Jiang HY, Li YC, Zhao PY, Yang GM, Liu X, Ren YF, Wang H. Exosomes derived from a mesenchymal-like endometrial regenerative cells ameliorate renal ischemia reperfusion injury through delivery of CD73. Stem Cell Res Ther 2025; 16:148. [PMID: 40140882 PMCID: PMC11948919 DOI: 10.1186/s13287-025-04275-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 03/11/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Renal ischemia reperfusion (I/R) injury is a major contributor to graft dysfunction and inflammation leading to graft loss. The deregulation of purinergic signaling has been implicated in the pathogenesis of renal I/R injury. CD73 and the generation of adenosine during purine metabolism to protect against renal I/R injury. A mesenchymal-like endometrial regenerative cell (ERC) has demonstrated a significant therapeutic effect on renal I/R injury. CD73 is a phenotypic marker of human endometrial regenerative cell exosomes (ERC-Exo). However, its immunosuppressive function in regulating purinergic metabolism has been largely neglected. Here, we investigate the protective effects and mechanism of ERC-Exo against renal I/R injury. METHODS Lentivirus-mediated CRISPR-Cas9 technology was employed to obtain CD73-specific knockout ERC-Exo (CD73-/-ERC-Exo). C57BL/6 mice who underwent unilateral ureteral obstruction were divided into the Untreated, ERC-Exo-treated, and CD73-/-ERC-Exo-treated groups. Renal function and pathological injury were assessed 3 days after renal reperfusion. The infiltration of CD4+ T cells and macrophages was analyzed by flow cytometry and immunofluorescence staining in kidneys. CD73-mediated immunosuppressive activity of ERC-Exo was investigated by bone marrow-derived macrophages (BMDM) co-culture assay in vitro. Flow cytometry determined macrophage polarization. ELISA and Treg proliferation assays detected the function of macrophages. Furthermore, the role of the MAPK pathway in CD73-positive Exo-induced macrophage polarization was also elucidated. RESULTS Compared with Untreated and CD73-/-ERC-Exo-treated groups, CD73-positive Exo effectively improved the serum creatinine (sCr), blood urea nitrogen (BUN), and necrosis and detachment of tubular epithelial cells, necrosis and proteinaceous casts induced by ischemia. CD73 improved the capacity of ERC-Exo on CD4+ T cell differentiation in the renal immune microenvironment. Surprisingly, ERC-Exosomal CD73 significantly decreased the populations of M1 cells but increased the proportions of M2 in kidneys. Furthermore, CD73-positive Exo markedly reduced the levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and increased anti-inflammatory factors (IL-10) level in kidneys. ERC-Exosomal CD73 improved macrophage immunoregulatory function associated with the MAPK pathway (including ERK1/2 and p38 pathways), which exerted a potent therapeutic effect against renal I/R. CONCLUSIONS These data collected insight into how ERC-Exo facilitated the hydrolysis of proinflammatory ATP to immunosuppressive ADO via CD73. CD73 is a critical modulator of the MAPK signaling pathway, inducing a polarization shift of macrophages towards an anti-inflammatory phenotype. This study highlights the significance of ERC-Exosomal CD73 in contributing to the therapeutic effects against renal I/R.
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Affiliation(s)
- Bo Shao
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Hong-da Wang
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Shao-Hua Ren
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
- Department of General Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Qiang Chen
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhao-Bo Wang
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Yi-Ni Xu
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Tong Liu
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Cheng-Lu Sun
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Yi-Yi Xiao
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Hong-Yu Jiang
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Yi-Cheng Li
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Peng-Yu Zhao
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Guang-Mei Yang
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Xu Liu
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Yu-Fan Ren
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Hao Wang
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China.
- Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin, China.
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Marrapu S, Kumar R. Transition from acute kidney injury to chronic kidney disease in liver cirrhosis patients: Current perspective. World J Nephrol 2025; 14:102381. [PMID: 40134649 PMCID: PMC11755238 DOI: 10.5527/wjn.v14.i1.102381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/22/2024] [Accepted: 01/11/2025] [Indexed: 01/20/2025] Open
Abstract
In liver cirrhosis patients, acute kidney injury (AKI) is a common and severe complication associated with significant morbidity and mortality, often leading to chronic kidney disease (CKD). This progression reflects a complex interplay of renal and hepatic pathophysiology, with AKI acting as an initiator through maladaptive repair mechanisms. These mechanisms-such as tubular cell cycle arrest, inflammatory cascades, and fibrotic processes-are exacerbated by the hemodynamic and neurohormonal disturbances characteristic of cirrhosis. Following AKI episodes, persistent kidney dysfunction or acute kidney disease (AKD) often serves as a bridge to CKD. AKD represents a critical phase in renal deterioration, characterized by prolonged kidney injury that does not fully meet CKD criteria but exceeds the temporal scope of AKI. The progression from AKD to CKD is further influenced by recurrent AKI episodes, impaired renal autoregulation, and systemic comorbidities such as diabetes and metabolic dysfunction-associated steatotic liver disease, which compound kidney damage. The clinical management of AKI and CKD in cirrhotic patients requires a multidimensional approach that includes early identification of kidney injury, the application of novel biomarkers, and precision interventions. Recent evidence underscores the inadequacy of traditional biomarkers in predicting the AKI-to-CKD progression, necessitating novel biomarkers for early detection and intervention.
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Affiliation(s)
- Sudheer Marrapu
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
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Marpaung FR, Purnami SW, Andari S, Rohman A, I’tishom R, Notobroto HB, Nugraha J, Prasetyo RV, Santoso D, Cavalier E, Aryati A. The varied Q creatinine in multi ethnics population and impact of adopting three different estimated glomerular filtration rates based on creatinine in adult populations: a call for performance validation. Front Med (Lausanne) 2025; 12:1467503. [PMID: 40196350 PMCID: PMC11973378 DOI: 10.3389/fmed.2025.1467503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 03/11/2025] [Indexed: 04/09/2025] Open
Abstract
Background The determination of kidney function is commonly done by estimating the glomerular filtration rate (eGFR) using serum creatinine levels. Various eGFR formulas, including the recently developed European Kidney Function Consortium (EKFC) and the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI), have been adopted and are commonly utilized in clinical settings. Nevertheless, the extent of acceptance among these formulations in the multi ethnics populace is still undetermined. Thus, this study aimed to evaluate the performance of these formulations across different glomerular filtration rate categories in the adult population. Methods The research involved a total of 9,557 individuals (median age of 40 years and 85% being male) who underwent routine medical examinations. Enzymatic or modified Jaffe techniques were employed to measure serum creatinine levels. The CKD-EPI2009 eGFR was employed as corresponding GFR in the comparisons. The Bland-Altman method was used to determine the average discrepancies and 95% confidence intervals of eGFR between each formula. Ultimately, in order to compare the equations, Lin's correlation coefficients were calculated for various eGFR categories. Results The median creatinine level in the different island population showed variability. The CKD-EPI 2009 as well as different equations showed categorical agreement within the range of 91.42 to 92.77%. The correlations between CKD-EPI2009 and CKD-EPI 2021 and EKFC were 0.998 and 0.79, respectively (p < 0.001). Conclusion A substantial variation in creatinine and eGFR assessment were observed among different eGFR analysis for the adult population. Prospective study in various clinical contexts using measured GFR is essential to validate eGFR.
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Affiliation(s)
- Ferdy Royland Marpaung
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Santi Wulan Purnami
- Department of Statistics, Institut Teknologi Sepuluh Nopember, Surabaya, Indonesia
| | - Shofi Andari
- Department of Statistics, Institut Teknologi Sepuluh Nopember, Surabaya, Indonesia
| | - Ali Rohman
- Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Surabaya, Indonesia
| | - Reny I’tishom
- Department of Biomedical Science, Universitas Airlangga, Surabaya, Indonesia
| | | | - Jusak Nugraha
- Department of Clinical Pathology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Risky Vitria Prasetyo
- Department of Child Health, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Djoko Santoso
- Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Etienne Cavalier
- Department of Clinical Chemistry, University of Liège, CIRM, CHU Sart Tilman, Liège, Belgium
| | - Aryati Aryati
- Department of Clinical Pathology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
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Adiyeke E, Ren Y, Fogel S, Rashidi P, Segal M, Shenkman EA, Bihorac A, Ozrazgat-Baslanti T. Epidemiology, trajectories and outcomes of acute kidney injury among hospitalized patients: a large retrospective multicenter cohort study. J Nephrol 2025:10.1007/s40620-025-02234-4. [PMID: 40113721 DOI: 10.1007/s40620-025-02234-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 02/03/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND Acute kidney injury (AKI) is a clinical syndrome affecting almost one-fifth of hospitalized patients, as well as over half of the patients who are admitted to the intensive care unit (ICU). Stratifying AKI patients into groups based on severity and duration would facilitate targeted efforts for treating AKI. METHODS In a retrospective, multicenter longitudinal cohort study of 2,187,254 hospital encounters from 935,679 patients who were admitted between 2012 and 2020 to health centers in the OneFlorida + Network, we analyzed the impact of AKI trajectories (i.e. rapidly reversed AKI, persistent AKI with renal recovery, and persistent AKI without renal recovery) on patients' clinical outcomes, including hospital, 30-day, 1-year, and 3-year mortality, kidney replacement therapy, new chronic kidney disease (CKD) within 90 days or 1-year of discharge, CKD progression within 1-year of discharge, resource utilization, hospital disposition, and major complications during hospitalization. RESULTS Among all encounters, 14% of patients had AKI, of whom 63%, 21%, and 16% had Stage 1, 2, and 3, respectively, as the worst AKI stage. The fraction of patients with persistent AKI was 31%. Patients with AKI had worse clinical outcomes and increased resource utilization compared to patients without the condition. One-year mortality was 5 times greater for patients with persistent AKI compared to those without AKI. CONCLUSIONS Persistent AKI was associated with prolonged hospitalization, increased ICU admission and greater mortality compared to the other groups. This may emphasize the critical need for devising strategies targeting effective management of AKI and prevention of persisting AKI.
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Affiliation(s)
- Esra Adiyeke
- Intelligent Clinical Care Center, University of Florida, Gainesville, FL, USA
- Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, PO Box 100224, Gainesville, FL, 32610-0224, USA
| | - Yuanfang Ren
- Intelligent Clinical Care Center, University of Florida, Gainesville, FL, USA
- Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, PO Box 100224, Gainesville, FL, 32610-0224, USA
| | - Shmuel Fogel
- Intelligent Clinical Care Center, University of Florida, Gainesville, FL, USA
- Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, PO Box 100224, Gainesville, FL, 32610-0224, USA
| | - Parisa Rashidi
- Intelligent Clinical Care Center, University of Florida, Gainesville, FL, USA
- Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA
| | - Mark Segal
- Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, PO Box 100224, Gainesville, FL, 32610-0224, USA
| | - Elizabeth A Shenkman
- Department of Health Outcomes and Biomedical Informatics, University of Florida, Gainesville, FL, USA
| | - Azra Bihorac
- Intelligent Clinical Care Center, University of Florida, Gainesville, FL, USA
- Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, PO Box 100224, Gainesville, FL, 32610-0224, USA
| | - Tezcan Ozrazgat-Baslanti
- Intelligent Clinical Care Center, University of Florida, Gainesville, FL, USA.
- Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, PO Box 100224, Gainesville, FL, 32610-0224, USA.
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Zajonz TS, Edinger F, Beran R, Sturm N, Yoerueker U, Akintuerk H, Mueller MF. Perioperative Incidence of Acute Renal Failure in Aortic Arch Reconstruction Using Retrograde Selective Lower Body Perfusion in Neonates and Infants. J Cardiothorac Vasc Anesth 2025:S1053-0770(25)00251-4. [PMID: 40221235 DOI: 10.1053/j.jvca.2025.03.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 03/13/2025] [Accepted: 03/17/2025] [Indexed: 04/14/2025]
Abstract
OBJECTIVE Examination of the impact of retrograde selective lower body perfusion (SLP) via a femoral arterial catheter on urine output and the incidence of acute kidney injury (AKI) during pediatric aortic arch reconstructions. The secondary objective was if the cannulation of the superficial femoral artery was associated with complications in the perfusion area. DESIGN A retrospective study over an 8-year period (January 2015 to December 2023). SETTING Pediatric heart center of a tertiary care hospital. PARTICIPANTS Neonates and infants (N = 104) undergoing elective aortic arch reconstruction with cardiopulmonary bypass, of whom 45 received retrograde SLP. INTERVENTIONS Retrograde SLP via ultrasound-guided, weight-adapted femoral artery catheters for retrograde perfusion during clamping of the descending aorta under surgery, compared to a control group with identical surgical, perfusion, and anesthesiologic management but without SLP. MEASUREMENTS AND MAIN RESULTS Perioperative AKI incidence was analyzed using KDIGO criteria at multiple predetermined time points, along with urinary output. The SLP group showed a significantly lower AKI incidence immediately and 6 hours postsurgery (p = 0.001). Higher urine output postoperatively until day 3 (p ≤ 0.045) in the SLP group. No vascular complications were observed until hospital discharge. CONCLUSIONS Retrograde SLP is associated with a reduced AKI incidence and increased postoperative urine output, without vascular complications. Further studies are needed to investigate the long-term effects of retrograde SLP on renal function.
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Affiliation(s)
- Thomas Simon Zajonz
- Pediatric Cardiac Anesthesiology Service, Pediatric Heart Centre, Department of Aaesthesiology Intensive Care Medicine, Pain Therapy, University Hospital Giessen and Marburg GmbH, Campus Giessen, Giessen, Germany.
| | - Fabian Edinger
- Pediatric Cardiac Anesthesiology Service, Pediatric Heart Centre, Department of Aaesthesiology Intensive Care Medicine, Pain Therapy, University Hospital Giessen and Marburg GmbH, Campus Giessen, Giessen, Germany
| | - Ronja Beran
- Department of Pediatric and Congenital Heart Surgery, Pediatric Heart Centre, University Hospital Giessen and Marburg GmbH, Campus Giessen, ießen Giessen, Germany
| | - Niklas Sturm
- Department of Pediatric and Congenital Heart Surgery, Pediatric Heart Centre, University Hospital Giessen and Marburg GmbH, Campus Giessen, ießen Giessen, Germany
| | - Uygar Yoerueker
- Department of Pediatric and Congenital Heart Surgery, Pediatric Heart Centre, University Hospital Giessen and Marburg GmbH, Campus Giessen, ießen Giessen, Germany
| | - Hakan Akintuerk
- Department of Pediatric and Congenital Heart Surgery, Pediatric Heart Centre, University Hospital Giessen and Marburg GmbH, Campus Giessen, ießen Giessen, Germany
| | - Matthias Friedrich Mueller
- Pediatric Cardiac Anesthesiology Service, Pediatric Heart Centre, Department of Aaesthesiology Intensive Care Medicine, Pain Therapy, University Hospital Giessen and Marburg GmbH, Campus Giessen, Giessen, Germany
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Cho NJ, Jeong I, Ahn SJ, Gil HW, Kim Y, Park JH, Kang S, Lee H. Machine Learning to Assist in Managing Acute Kidney Injury in General Wards: Multicenter Retrospective Study. J Med Internet Res 2025; 27:e66568. [PMID: 40101226 PMCID: PMC11962325 DOI: 10.2196/66568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 01/10/2025] [Accepted: 02/14/2025] [Indexed: 03/20/2025] Open
Abstract
BACKGROUND Most artificial intelligence-based research on acute kidney injury (AKI) prediction has focused on intensive care unit settings, limiting their generalizability to general wards. The lack of standardized AKI definitions and reliance on intensive care units further hinder the clinical applicability of these models. OBJECTIVE This study aims to develop and validate a machine learning-based framework to assist in managing AKI and acute kidney disease (AKD) in general ward patients, using a refined operational definition of AKI to improve predictive performance and clinical relevance. METHODS This retrospective multicenter cohort study analyzed electronic health record data from 3 hospitals in South Korea. AKI and AKD were defined using a refined version of the Kidney Disease: Improving Global Outcomes criteria, which included adjustments to baseline serum creatinine estimation and a stricter minimum increase threshold to reduce misclassification due to transient fluctuations. The primary outcome was the development of machine learning models for early prediction of AKI (within 3 days before onset) and AKD (nonrecovery within 7 days after AKI). RESULTS The final analysis included 135,068 patients. A total of 7658 (8%) patients in the internal cohort and 2898 (7.3%) patients in the external cohort developed AKI. Among the 5429 patients in the internal cohort and 1998 patients in the external cohort for whom AKD progression could be assessed, 896 (16.5%) patients and 287 (14.4%) patients, respectively, progressed to AKD. Using the refined criteria, 2898 cases of AKI were identified, whereas applying the standard Kidney Disease: Improving Global Outcomes criteria resulted in the identification of 5407 cases. Among the 2509 patients who were not classified as having AKI under the refined criteria, 2242 had a baseline serum creatinine level below 0.6 mg/dL, while the remaining 267 experienced a decrease in serum creatinine before the onset of AKI. The final selected early prediction model for AKI achieved an area under the receiver operating characteristic curve of 0.9053 in the internal cohort and 0.8860 in the external cohort. The early prediction model for AKD achieved an area under the receiver operating characteristic curve of 0.8202 in the internal cohort and 0.7833 in the external cohort. CONCLUSIONS The proposed machine learning framework successfully predicted AKI and AKD in general ward patients with high accuracy. The refined AKI definition significantly reduced the classification of patients with transient serum creatinine fluctuations as AKI cases compared to the previous criteria. These findings suggest that integrating this machine learning framework into hospital workflows could enable earlier interventions, optimize resource allocation, and improve patient outcomes.
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Affiliation(s)
- Nam-Jun Cho
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
| | - Inyong Jeong
- Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Se-Jin Ahn
- Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Hyo-Wook Gil
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
| | - Yeongmin Kim
- Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jin-Hyun Park
- Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Sanghee Kang
- Department of Surgery, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Hwamin Lee
- Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Republic of Korea
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Cowan AC, Jeyakumar N, Garg AX, Dixon S, Luo B, Blake PG. Approximating the Proportion of Individuals With Kidney Failure Who Die Without Kidney Replacement Therapy in Ontario, Canada. Can J Kidney Health Dis 2025; 12:20543581251323961. [PMID: 40091887 PMCID: PMC11909665 DOI: 10.1177/20543581251323961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 01/07/2025] [Indexed: 03/19/2025] Open
Abstract
Background Quantifying the number and proportion of people with kidney failure (KF) who receive conservative kidney management is vital for health care system benchmarking and planning. It is not easy to ascertain this value precisely at the population level, but we can approximate it using information from different data sources to estimate the proportion of patients with advanced kidney disease who die without receiving dialysis or a transplant and should receive conservative kidney management. Objective To approximate the proportion of people with KF in Ontario, Canada, who die without receiving kidney replacement therapy. Design A review of unpublished provincial renal agency reports of 3 retrospective population-based cohorts combined with clinical interpretation. Patients The 3 cohorts of people were: 1. those who died between January 1, 2013 and December 31, 2017, with an estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m2 and no evidence of receiving kidney replacement therapy; 2. those who initiated outpatient maintenance dialysis or received a preemptive transplant in the same period; and 3. those with a sustained low eGFR ≤ 10 mL/min/1.73 m2 between April 1, 2015 and March 31, 2018, and were followed for 1 year to determine if they started dialysis. In this last cohort, patients whose kidney function improved (evidence of an eGFR > 10 mL/min/1.73 m2) or who received a transplant during follow-up were excluded from the analysis. Measurements and Methods The 3 cohorts were derived at ICES and used linked health care databases for the province of Ontario, Canada. In 2016, Ontario had a population of about 14 million people. Two nephrologists reviewed the data to provide the clinical approximation. Results There were 1891 individuals with KF who died without kidney replacement (the no KRT cohort). The median (25th, 75th percentile) eGFR prior to death was 7 (5, 8) mL/min/1.73 m2. During the same period, 13 511 individuals started dialysis or received a preemptive kidney transplant (the KRT cohort). There were 7259 individuals in the low eGFR cohort; over the following year, 66% started dialysis, 20% died without dialysis, and 14% were alive without starting dialysis. The clinical approximation is that between 13 and 16% of people with KF die without receiving kidney replacement therapy. Limitations The data reports lacked certain information to inform the clinical approximation. There was no information on the conversations health professionals had with people about kidney replacement therapy, any decisions made about receiving conservative care, or the circumstances that preceded death without kidney replacement therapy. Conclusions After reviewing data from the 3 cohorts, we clinically approximate that 1 in 6 people with KF in Ontario, Canada, die without receiving dialysis and should receive conservative kidney management.
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Affiliation(s)
- Andrea C Cowan
- ICES, London, ON, Canada
- Department of Medicine, Western University, London, ON, Canada
- Department of Epidemiology & Biostatistics, Western University, London, ON, Canada
| | - Nivethika Jeyakumar
- ICES, London, ON, Canada
- London Health Sciences Research Institute, ON, Canada
| | - Amit X Garg
- ICES, London, ON, Canada
- Department of Medicine, Western University, London, ON, Canada
- Department of Epidemiology & Biostatistics, Western University, London, ON, Canada
- London Health Sciences Research Institute, ON, Canada
| | | | - Bin Luo
- ICES, London, ON, Canada
- London Health Sciences Research Institute, ON, Canada
| | - Peter G Blake
- Department of Medicine, Western University, London, ON, Canada
- London Health Sciences Research Institute, ON, Canada
- Ontario Renal Network, Ontario Health, Toronto, Canada
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Udeze CO, Nwobodo MU, Afolabi OF, Ifeanyi C, Nwikwu OJ, Agbo AC, Ologwu C, Ifebunandu NA, Ulasi II. Incidence, risk factors and outcomes of AKI among trauma patients in a tertiary hospital in south-east, Nigeria. BMC Nephrol 2025; 26:135. [PMID: 40082833 PMCID: PMC11908019 DOI: 10.1186/s12882-025-04062-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 03/07/2025] [Indexed: 03/16/2025] Open
Abstract
BACKGROUND Acute kidney injury is a preventable and treatable complication of trauma-related injuries associated with increased mortality. Data on the burden and predisposing factors to the development of AKI following trauma are lacking in our environment. This study aims to evaluate the incidence, predisposing risk factors, and short-term outcomes of AKI in trauma patients seen at the Accident and Emergency Unit of Alex Ekwueme Federal University Teaching Hospital Abakaliki, Nigeria. METHODS The study was a hospital-based cohort study of trauma patients. Consenting patients presenting after a trauma-related event were enrolled. Socio-demographic data, the time of the incident, the time of presentation to the hospital, the nature and extent of injuries, and the treatment received were recorded. Blood was taken at specified intervals for haemoglobin, white blood cell count, serum urea, and creatinine estimation. AKI was defined based on the Kidney Disease: Improving Global Outcomes guidelines. Multivariate logistic regression analysis was applied to determine independent risk factors for AKI in trauma patients. RESULTS 186 trauma patients participated; 83.3% were males. The patients' mean age was 35.3 (± 11.1) years, and most were traders (31.7%). The commonest mechanism of trauma was road traffic accidents (62.9%). The incidence of AKI in this study was 27 (14.5%). Multivariate logistic regression analysis showed that the development of AKI was independently associated with injuries complicated by fractures and longer hospital stay. The 30-day outcome was: 26 (96.3%) recovered fully, and 1 (3.7%) had AKI requiring renal replacement therapy, with no in-hospital mortality. CONCLUSION AKI is a frequent complication of trauma, and trauma patients presenting with fractures and have prolonged hospital stay require closer monitoring and care.
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Affiliation(s)
- Chinedu O Udeze
- Nephrology Division, Department of Internal Medicine, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria.
| | - Monday U Nwobodo
- Nephrology Division, Department of Internal Medicine, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria
| | - Olaronke F Afolabi
- Nephrology Division, Department of Internal Medicine, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria
| | - Chinaka Ifeanyi
- Nephrology Division, Department of Internal Medicine, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria
| | - Onyinye J Nwikwu
- Nephrology Division, Department of Internal Medicine, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria
| | - Anthony C Agbo
- Nephrology Division, Department of Internal Medicine, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria
| | - Christiana Ologwu
- Nephrology Division, Department of Internal Medicine, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria
| | - Ngozi A Ifebunandu
- Nephrology Division, Department of Internal Medicine, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria
| | - Ifeoma I Ulasi
- Nephrology Division, Department of Internal Medicine, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria
- Department of Medicine, College of Medicine, University of Nigeria, Ituku-Ozalla/ University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu State, Nigeria
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Xiao Y, Liu C, Liu Y, Luo H, Zhu Y, Zhou L, Gao Y, Zhang H, Chen R, Xuan J, Kan H. Association between air pollution and hospitalization for acute exacerbation of kidney failure: A nationwide time-stratified case-crossover study in China. JOURNAL OF HAZARDOUS MATERIALS 2025; 485:136834. [PMID: 39675085 DOI: 10.1016/j.jhazmat.2024.136834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 11/22/2024] [Accepted: 12/08/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND Air pollution is a potential risk factor for kidney disease; however, the impact on kidney failure exacerbation is underexplored. This study assessed the short-term effects of air pollution on hospitalization for kidney failure exacerbation. METHODS This nationwide, time-stratified, case-crossover study included 45,249 hospitalized patients with kidney failure from 153 hospitals in 20 Chinese provinces between 2013 and 2020. Air pollutant concentrations were obtained from the closest monitoring stations. Conditional logistic regression models were used to determine the associations between air pollutants and hospitalizations, with exposure-response curves fitted and stratified analyses conducted. RESULTS For each interquartile range increase in pollutants (lag 0-2 days), there was a significant increase in kidney failure hospitalization: 3.46 % for PM2.5, 3.64 % for PM2.5-10, 7.88 % for NO2, and 4.37 % for CO. No significant associations were observed for O3 and SO2. NO2 had a linear exposure-response curve; PM2.5 and PM2.5-10 showed stronger effects at lower exposures, while CO's effect increased at higher exposures. Furthermore, the impact was greater during the cold season. CONCLUSIONS This large-scale national study highlights the significant association between short-term exposure to PM2.5, PM2.5-10, NO2, and CO and kidney failure exacerbation, providing novel insights into the combined effects of air pollution on kidney failure.
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Affiliation(s)
- Yalan Xiao
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Cong Liu
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Yichen Liu
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Huihuan Luo
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Yixiang Zhu
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Lu Zhou
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Ya Gao
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Hongliang Zhang
- Department of Environmental Science and Engineering, Fudan University, Shanghai 200438, China
| | - Renjie Chen
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Jianwei Xuan
- Health Economic Research Institute, School of Pharmacy, Sun Yat-Shen University, Guangzhou 510275, China
| | - Haidong Kan
- Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China; National Center for Children's Health, Children's Hospital of Fudan University, Shanghai 201102, China.
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Yang H, Chen Y, He J, Li Y, Feng Y. Advances in the diagnosis of early biomarkers for acute kidney injury: a literature review. BMC Nephrol 2025; 26:115. [PMID: 40045274 PMCID: PMC11884078 DOI: 10.1186/s12882-025-04040-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 02/21/2025] [Indexed: 03/09/2025] Open
Abstract
Acute kidney injury (AKI) is a critical condition with diverse manifestations and variable outcomes. Its diagnosis traditionally relies on delayed indicators such as serum creatinine and urine output, making early detection challenging. Early identification is essential to improving patient outcomes, driving the need for novel biomarkers. Recent advancements have identified promising biomarkers across various biological processes. Tubular injury markers, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP), offer insights into early tubular damage. Inflammatory and repair-associated biomarkers, such as interleukin-18 (IL-18), monocyte chemotactic protein-1 (MCP-1), osteopontin (OPN), and C-C motif chemokine ligand 14 (CCL14), reflect ongoing injury and recovery processes. Additionally, stress and repair markers like tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP-7), alongside filtration markers such as cystatin C (CysC) and proenkephalin (PenKid®) e.tal, further enhance diagnostic precision. Oxidative stress-related markers, including Superoxide Dismutase 1 (SOD1), also contribute valuable information. Emerging candidates, such as microRNAs, soluble urokinase plasminogen activator receptor (SuPAR), and chitinase-3-like protein 1 (CHI3L1), hold substantial promise for AKI detection and prognosis. This review summarizes the progress in AKI biomarker research, highlighting their clinical utility and exploring their potential to refine early diagnosis and management strategies. These findings offer a new perspective for integrating novel biomarkers into routine clinical practice, ultimately improving AKI care.
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Affiliation(s)
- Hongsha Yang
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Yanqin Chen
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Jiajia He
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Yi Li
- Department of Nephrology, Institute of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Centre for Kidney Diseases, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Yunlin Feng
- Department of Nephrology, Institute of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Centre for Kidney Diseases, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
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Steenvoorden TS, de Kruijf KC, Appelman B, Moggre B, Bos LDJ, Vlaar APJ, Douma RA, Uhel F, Kers J, Oppelaar JJ, van Vught LA, Beudel M, Elbers PWG, Wiersinga WJ, van der Poll T, Vogt L, Peters-Sengers H. Host Response Protein Biomarkers Indicative of Persistent Acute Kidney Injury in Critically Ill COVID-19 Patients. Crit Care Explor 2025; 7:e1222. [PMID: 40079888 PMCID: PMC11908758 DOI: 10.1097/cce.0000000000001222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/15/2025] Open
Abstract
IMPORTANCE Sepsis-related host-response anomalies contribute to acute kidney injury (AKI) duration. Data on the host-response specific to COVID-19-associated AKI (COVID-AKI) in critically ill patients is limited. OBJECTIVES We postulated that persistent COVID-AKI (> 48 hr) differs in host response from transient (< 48 hr) or no COVID-AKI. DESIGN, SETTING, AND PARTICIPANTS This prospective biomarker study observed patients with severe acute respiratory syndrome coronavirus 2 infection, without chronic kidney disease, in three ICUs from March 2020 to July 2020. AKI was assessed by hourly urine output and daily plasma creatinine. MAIN OUTCOMES AND MEASURES Luminex and enzyme-linked immunosorbent assay were used to analyze 48 plasma protein biomarkers across six pathophysiological domains, which were tested with mixed-effects models. RESULTS Of 177 included patients, 106 (59.9%) had AKI within the first 48 hours of admission, of whom 76 (71.7%) had persistent AKI and 30 (28.3%) transient AKI. Those with persistent AKI often had obesity, hypertension, and a higher Sequential Organ Failure Assessment score due to the renal component. Longitudinal analyses revealed that seven proteins were elevated in persistent AKI compared with no AKI. These were related to inflammation (triggering receptor expressed on myeloid cells 1, p < 0.001; tumor necrosis factor receptor 1, p < 0.001; procalcitonin, p = 0.001), complement activation (mannan-binding lectin serine protease-2, p = 0.001), kidney dysfunction (cystatin C, p < 0.001; neutrophil gelatinase-associated lipocalin, p < 0.001), and lung dysfunction (Clara cell secretory protein 16, p < 0.001). AKI (duration) was not associated with differences in the cytokine signaling, endothelial cell activation, or coagulation domains. CONCLUSIONS AND RELEVANCE In contrast with sepsis-associated AKI, primarily inflammation-related biomarker levels correlated with COVID-AKI persistence. This study offers insights into COVID-AKI and may guide approaches to mitigate its persistence.
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Affiliation(s)
- Thei S. Steenvoorden
- Department of Internal Medicine Nephrology Section, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Koen C. de Kruijf
- Department of Internal Medicine Nephrology Section, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Brent Appelman
- Center for Experimental and Molecular Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- The Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Bas Moggre
- Department of Internal Medicine Nephrology Section, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Lieuwe D. J. Bos
- Department of Intensive Care, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Alexander P. J. Vlaar
- Department of Intensive Care, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Reneé A. Douma
- Department of Internal Medicine, Flevo Hospital, Almere, The Netherlands
| | - Fabrice Uhel
- Center for Experimental and Molecular Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- The Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jesper Kers
- Department of Pathology, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- Department of Pathology, Leiden Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
- Van ‘t Hoff Institute for Molecular Sciences, University of Amsterdam, Amsterdam, The Netherlands
| | - Jetta J. Oppelaar
- Department of Internal Medicine Nephrology Section, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Lonneke A. van Vught
- Center for Experimental and Molecular Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- Department of Intensive Care, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Martijn Beudel
- Department of Neurology, Amsterdam University Medical Centers, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, The Netherlands
| | - Paul W. G. Elbers
- Department of Intensive Care, Amsterdam UMC, Location VU Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - W. Joost Wiersinga
- Center for Experimental and Molecular Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- The Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Division of Infectious Diseases, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Tom van der Poll
- Center for Experimental and Molecular Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- The Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Division of Infectious Diseases, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Liffert Vogt
- Department of Internal Medicine Nephrology Section, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Hessel Peters-Sengers
- Center for Experimental and Molecular Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- The Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Epidemiology and Data Science, Amsterdam UMC, Location VU, Amsterdam, The Netherlands
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49
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de Faria NP, Suassuna JHR, de Souza CAM, Freire SM, Gomes CLR. Acute kidney injury in the pandemic years revisited: distinct patterns of staging and recovery in patients with and without COVID-19. J Nephrol 2025; 38:609-620. [PMID: 40042786 DOI: 10.1007/s40620-024-02180-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 11/27/2024] [Indexed: 04/03/2025]
Abstract
BACKGROUND Acute kidney injury (AKI) is a frequent and severe complication in COVID-19 patients, associated with poor outcomes. This study evaluates the characteristics and outcomes of AKI in COVID-19-positive versus negative patients during the pandemic in an emerging country, emphasizing differences in incidence, recovery, and healthcare resource utilization. METHODS We conducted a retrospective cohort study including 9112 intensive care unit (ICU) patients from two major hospitals in Brazil, hospitalized between March 2020 and April 2022. Statistical analyses included logistic regression, Kaplan-Meier survival analysis, and time series analysis of AKI trends across COVID-19 waves. RESULTS 2333 patients (25.6%) tested positive for COVID-19. AKI incidence (79.7% vs. 52.6%, p < 0.001) and severity (Stage 3: 48.6% vs. 26.6%, p < 0.001) were significantly higher in the COVID-19-positive group. COVID-19 patients with AKI had longer ICU stays (median 11 vs. four days, p < 0.001) and higher mechanical ventilation needs (57.9% vs. 31.1%, p < 0.001). COVID-19 independently increased the risk of AKI (OR 2.03, CI 1.77-2.32); the coexistence of COVID-19 and AKI conferred significantly higher odds for mortality (OR 8.53, CI 6.67-11.02). Kidney recovery was less frequent in COVID-19 patients, with a higher incidence of acute kidney disease in survivors (OR 1.99, CI 1.74-2.28). Sensitivity analysis of septic patients confirmed higher AKI incidence and mortality in COVID-19 patients. CONCLUSION COVID-19 significantly affects AKI incidence, severity, and recovery, particularly in resource-limited settings. These findings emphasize the need for targeted strategies to manage kidney complications during pandemics and stress the importance of healthcare system preparedness in emerging countries.
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Affiliation(s)
- Natália Piazzi de Faria
- Clinical and Academic Unit of Nephrology, Faculty of Medical Sciences, Pedro Ernesto University Hospital, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - José Hermógenes Rocco Suassuna
- Clinical and Academic Unit of Nephrology, Faculty of Medical Sciences, Pedro Ernesto University Hospital, Rio de Janeiro State University, Rio de Janeiro, Brazil
- Kidney Assistance LLC, Rio de Janeiro, Brazil
- Americas Medical Complex, Rio de Janeiro, Brazil
| | - Carlos Augusto Moreira de Souza
- Department of Information, Technologies and Health Education (DTIES), Faculty of Medical Sciences, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Sérgio Miranda Freire
- Department of Information, Technologies and Health Education (DTIES), Faculty of Medical Sciences, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Conrado Lysandro R Gomes
- Clinical and Academic Unit of Nephrology, Faculty of Medical Sciences, Pedro Ernesto University Hospital, Rio de Janeiro State University, Rio de Janeiro, Brazil.
- Kidney Assistance LLC, Rio de Janeiro, Brazil.
- Americas Medical Complex, Rio de Janeiro, Brazil.
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50
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Steenvoorden TS, Evers L, Vogt L, Rood JAJ, Kers J, Baas MC, Christiaans MHL, Lindeman JHN, Sanders JSF, de Vries APJ, van Zuilen AD, Bemelman FJ, Peters-Sengers H. The differential impact of early graft dysfunction in kidney donation after brain death and after circulatory death: Insights from the Dutch National Transplant Registry. Am J Transplant 2025; 25:556-566. [PMID: 39343037 DOI: 10.1016/j.ajt.2024.09.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 08/23/2024] [Accepted: 09/22/2024] [Indexed: 10/01/2024]
Abstract
Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcomes. Using competing risk and Cox-regression analysis, we compared death-censored graft loss between types of early graft function: DGF (temporary dialysis dependency started within 7 days after transplantation), slow graft function (3-day plasma creatinine decline less than 10% per day), and immediate graft function. In 1061 DBD and 1605 DCD graft recipients (January 2014 until January 2023), graft survival was similar. DGF was associated with death-censored graft loss in DBD and DCD (adjusted hazard ratios: DGF in DBD: 1.79 [1.04-2.91], P = .027, DGF in DCD: 1.84 [1.18-2.87], P = .008; Reference: no DGF). Slow graft function was associated with death-censored graft loss in DBD, but not significantly in DCD (adjusted hazard ratios DBD: 2.82 (1.34-5.93), P = .007, and DCD: 1.54 (0.72-3.35), P = .262; Reference: immediate graft function). Early graft dysfunction has a differential impact on graft outcome in DBD and DCD. The differences between DBD and DCD should be accounted for in research and the clinic.
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Affiliation(s)
- Thei S Steenvoorden
- Department of Internal Medicine, Section Nephrology, Amsterdam UMC, location AMC, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, The Netherlands.
| | - Lara Evers
- Department of Internal Medicine, Section Nephrology, Amsterdam UMC, location AMC, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, The Netherlands
| | - Liffert Vogt
- Department of Internal Medicine, Section Nephrology, Amsterdam UMC, location AMC, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, The Netherlands
| | - Janneke A J Rood
- Department of Internal Medicine, Section Nephrology, Amsterdam UMC, location VUmc, Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands
| | - Jesper Kers
- Department of Pathology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, The Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands; Biomolecular Systems Analytics, Van 't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, Amsterdam, The Netherlands
| | - Marije C Baas
- Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Maarten H L Christiaans
- Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Jan H N Lindeman
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Jan-Stephan F Sanders
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands
| | - Aiko P J de Vries
- Department of Medicine, Division of Nephrology, and Leiden Transplant Center, Leiden University Medical Center and Leiden University, Leiden, The Netherlands
| | - Arjan D van Zuilen
- Department of Nephrology and Hypertension, UMC Utrecht, Utrecht, The Netherlands
| | - Frederike J Bemelman
- Department of Internal Medicine, Section Nephrology, Amsterdam UMC, location AMC, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, The Netherlands
| | - Hessel Peters-Sengers
- Center of Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands; Department of Epidemiology and Data Science, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, The Netherlands
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