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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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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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Trask-Marino AL, Marino B, Lancefield TF, See EJ, May CN, Booth LC, Raman J, Lankadeva YR. Renal macro- and microcirculatory perturbations in acute kidney injury and chronic kidney disease associated with heart failure and cardiac surgery. Am J Physiol Renal Physiol 2025; 328:F452-F469. [PMID: 39918776 DOI: 10.1152/ajprenal.00266.2024] [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: 09/13/2024] [Revised: 10/02/2024] [Accepted: 01/28/2025] [Indexed: 03/15/2025] Open
Abstract
Chronic kidney disease (CKD) affects 50% of patients with heart failure. The pathophysiology of CKD in heart failure is proposed to be driven by macrocirculatory hemodynamic changes, including reduced cardiac output and elevated central venous pressure. However, our understanding of renal microcirculation in heart failure and CKD remains limited. This is largely due to the lack of noninvasive techniques to assess renal microcirculation in patients. Moreover, there is a lack of clinically relevant animal models of heart failure and CKD to advance our understanding of the timing and magnitude of renal microcirculatory dysfunction. Patients with heart failure and CKD commonly require cardiac surgery with cardiopulmonary bypass (CPB) to improve their prognosis. However, acute kidney injury (AKI) is a frequent unresolved clinical complication in these patients. There is emerging evidence that renal microcirculatory dysfunction, characterized by renal medullary hypoperfusion and hypoxia, plays a critical role in the pathogenesis of cardiac surgery-associated AKI. In this review, we consolidate the preclinical and clinical evidence of renal macro- and microcirculatory perturbations in heart failure and cardiac surgery requiring CPB. We also examine emerging biomarkers and therapies that may improve health outcomes for this vulnerable patient population by targeting the renal microcirculation.
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Affiliation(s)
| | - Bruno Marino
- Cellsaving and Perfusion Resources, Melbourne, Victoria, Australia
| | | | - Emily J See
- Department of Critical Care, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Department of Intensive Care, Austin Hospital, Heidelberg, Victoria, Australia
| | - Clive N May
- Preclinical Critical Care Unit, The Florey, Melbourne, Victoria, Australia
- Department of Critical Care, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia
| | - Lindsea C Booth
- Preclinical Critical Care Unit, The Florey, Melbourne, Victoria, Australia
| | - Jai Raman
- Department of Cardiothoracic Surgery, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia
- Townsville University Hospital, Townsville, Queensland, Australia
| | - Yugeesh R Lankadeva
- Preclinical Critical Care Unit, The Florey, Melbourne, Victoria, Australia
- Department of Critical Care, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Anaesthesia, Austin Hospital, Heidelberg, Victoria, Australia
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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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Ostermann M, Lumlertgul N, Jeong R, See E, Joannidis M, James M. Acute kidney injury. Lancet 2025; 405:241-256. [PMID: 39826969 DOI: 10.1016/s0140-6736(24)02385-7] [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: 07/23/2024] [Revised: 10/01/2024] [Accepted: 10/25/2024] [Indexed: 01/22/2025]
Abstract
Acute kidney injury (AKI) is a common, heterogeneous, multifactorial condition, which is part of the overarching syndrome of acute kidney diseases and disorders. This condition's incidence highest in low-income and middle-income countries. In the short term, AKI is associated with increased mortality, an increased risk of complications, extended stays in hospital, and high health-care costs. Long-term complications include chronic kidney disease, kidney failure, cardiovascular morbidity, and an increased risk of death. Several strategies are available to prevent and treat AKI in specific clinical contexts. Otherwise, AKI care is primarily supportive, focused on treatment of the underlying cause, prevention of further injury, management of complications, and short-term renal replacement therapy in case of refractory complications. Evidence confirming that AKI subphenotyping is necessary to identify precision-oriented interventions is growing. Long-term follow-up of individuals recovered from AKI is recommended but the most effective models of care remain unclear.
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Affiliation(s)
- Marlies Ostermann
- Department of Critical Care, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, UK.
| | - Nuttha Lumlertgul
- Excellence Centre for Critical Care Nephrology, Division of Nephrology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Rachel Jeong
- Division of Nephrology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Emily See
- Departments of Intensive Care, Royal Melbourne Hospital, Melbourne, VIC, Australia; Department of Nephrology, Royal Melbourne Hospital, Melbourne, VIC, Australia; Department of Critical Care, University of Melbourne, Melbourne, VIC, Australia
| | - Michael Joannidis
- Division of Emergency Medicine and Intensive Care, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria
| | - Matthew James
- Division of Nephrology, Department of Medicine, O'Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, O'Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Roy A, Mehtani R, Kulkarni AV. Acute Kidney Injury in Cirrhosis Revisited-Implications in Clinical Practice. GASTRO HEP ADVANCES 2024; 4:100583. [PMID: 39911499 PMCID: PMC11795086 DOI: 10.1016/j.gastha.2024.10.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 10/29/2024] [Indexed: 02/07/2025]
Affiliation(s)
- Akash Roy
- Institute of Gastrosciences and Liver Transplantation, Apollo Multispeciality Hospitals, Kolkata, India
| | - Rohit Mehtani
- Department of Hepatology, Amrita Institute of Medical Sciences and Research Centre, Faridabad, Haryana, India
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Wang X, Xu L, Guan C, Xu D, Che L, Wang Y, Man X, Li C, Xu Y. Machine learning-based risk prediction of acute kidney disease and hospital mortality in older patients. Front Med (Lausanne) 2024; 11:1407354. [PMID: 39211338 PMCID: PMC11357947 DOI: 10.3389/fmed.2024.1407354] [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: 03/26/2024] [Accepted: 07/29/2024] [Indexed: 09/04/2024] Open
Abstract
Introduction Acute kidney injury (AKI) is a prevalent complication in older people, elevating the risks of acute kidney disease (AKD) and mortality. AKD reflects the adverse events developing after AKI. We aimed to develop and validate machine learning models for predicting the occurrence of AKD, AKI and mortality in older patients. Methods We retrospectively reviewed the medical records of older patients (aged 65 years and above). To explore the trajectory of kidney dysfunction, patients were categorized into four groups: no kidney disease, AKI recovery, AKD without AKI, or AKD with AKI. We developed eight machine learning models to predict AKD, AKI, and mortality. The best-performing model was identified based on the area under the receiver operating characteristic curve (AUC) and interpreted using the Shapley additive explanations (SHAP) method. Results A total of 22,005 patients were finally included in our study. Among them, 4,434 patients (20.15%) developed AKD, 4,000 (18.18%) occurred AKI, and 866 (3.94%) patients deceased. Light gradient boosting machine (LGBM) outperformed in predicting AKD, AKI, and mortality, and the final lite models with 15 features had AUC values of 0.760, 0.767, and 0.927, respectively. The SHAP method revealed that AKI stage, albumin, lactate dehydrogenase, aspirin and coronary heart disease were the top 5 predictors of AKD. An online prediction website for AKD and mortality was developed based on the final models. Discussion The LGBM models provide a valuable tool for early prediction of AKD, AKI, and mortality in older patients, facilitating timely interventions. This study highlights the potential of machine learning in improving older adult care, with the developed online tool offering practical utility for healthcare professionals. Further research should aim at external validation and integration of these models into clinical practice.
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Affiliation(s)
- Xinyuan Wang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lingyu Xu
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chen Guan
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Daojun Xu
- Department of Nephrology, Linyi People's Hospital, Linyi, 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
| | - Chenyu Li
- 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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Maeda A, Inokuchi R, Bellomo R, Doi K. Heterogeneity in the definition of major adverse kidney events: a scoping review. Intensive Care Med 2024; 50:1049-1063. [PMID: 38801518 PMCID: PMC11245451 DOI: 10.1007/s00134-024-07480-x] [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: 02/29/2024] [Accepted: 05/03/2024] [Indexed: 05/29/2024]
Abstract
Acute kidney injury (AKI) is associated with persistent renal dysfunction, the receipt of dialysis, dialysis dependence, and mortality. Accordingly, the concept of major adverse kidney events (MAKE) has been adopted as an endpoint for assessing the impact of AKI. However, applied criteria or observation periods for operationalizing MAKE appear to vary across studies. To evaluate this heterogeneity for MAKE evaluation, we performed a systematic scoping review of studies that employed MAKE as an AKI endpoint. Four major academic databases were searched, and we identified 122 studies with increasing numbers over time. We found marked heterogeneity in applied criteria and observation periods for MAKE across these studies, with some even lacking a description of criteria. Moreover, 13 different observation periods were employed, with 30 days and 90 days as the most common. Persistent renal dysfunction was evaluated by estimated glomerular filtration rate (34%) or serum creatinine concentration (48%); however, 37 different definitions for this component were employed in terms of parameters, cut-off criteria, and assessment periods. The definition for the dialysis component also showed significant heterogeneity regarding assessment periods and duration of dialysis requirement (chronic vs temporary). Finally, MAKE rates could vary by 7% [interquartile range: 1.7-16.7%] with different observation periods or by 36.4% with different dialysis component definitions. Our findings revealed marked heterogeneity in MAKE definitions, particularly regarding component assessment and observation periods. Dedicated discussion is needed to establish uniform and acceptable standards to operationalize MAKE in terms of selection and applied criteria of components, observation period, and reporting criteria for future trials on AKI and related conditions.
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Affiliation(s)
- Akinori Maeda
- Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia
- Department of Emergency and Critical Care Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Ryota Inokuchi
- Department of Emergency and Critical Care Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
- Department of Clinical Engineering, The University of Tokyo Hospital, Tokyo, Japan
| | - Rinaldo Bellomo
- Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia
- Data Analytics Research and Evaluation Centre, The University of Melbourne and Austin Hospital, Melbourne, VIC, Australia
- Department of Critical Care, The University of Melbourne, Melbourne, VIC, Australia
- Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia
- Department of Intensive Care, The Royal Melbourne Hospital, Melbourne, Australia
| | - Kent Doi
- Department of Emergency and Critical Care Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
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Suppadungsuk S, Thongprayoon C, Nikravangolsefid N, Singh W, Cheungpasitporn W, Dong Y, Kashani KB. Magnesium Derangement among Critically Ill Patients with Acute Kidney Injury: An Association with Acute Kidney Disease. Nephron Clin Pract 2024; 148:553-562. [PMID: 38861941 DOI: 10.1159/000539674] [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: 04/01/2024] [Accepted: 05/28/2024] [Indexed: 06/13/2024] Open
Abstract
INTRODUCTION The association between magnesium level and progression to acute kidney disease (AKD) in acute kidney injury (AKI) patients was not well studied. With AKI transition to AKD, the burden of the disease on mortality, morbidity, and healthcare costs increases. Serum magnesium disturbances are linked with a decline in renal function and increased risk of death in CKD and hemodialysis patients. This study aims to assess the significance of magnesium derangements as a risk factor for the progression of AKI to AKD in critically ill patients. METHODS This study was conducted among patients with AKI admitted to the intensive care units at Mayo Clinic from 2007 to 2017. Serum magnesium at AKI onset was categorized into five groups of <1.7, 1.7-1.9, 1.9-2.1, 2.1-2.3, and ≥2.3 mg/dL, with 1.9-2.1 mg/dL as the reference group. AKD was defined as AKI that persisted >7 days following the AKI onset. Logistic regression was used to evaluate the association between magnesium and AKD. RESULTS Among 20,198 critically ill patients with AKI, the mean age was 66 ± 16 years, and 57% were male. The mean serum magnesium at AKI onset was 1.9 ± 0.4 mg/dL. The overall incidence of AKD was 31.4%. The association between serum magnesium and AKD followed a U-shaped pattern. In multivariable analysis, serum magnesium levels were associated with increased risk of AKD with the odds ratio of 1.17 (95% CI: 1.07-1.29), 1.13 (95% CI: 1.01-1.26), and 1.65 (95% CI: 1.48-1.84) when magnesium levels were <1.7, 2.1-2.3, and ≥2.3 mg/dL, respectively. CONCLUSION Among patients with AKI, magnesium level derangement was an independent risk for AKD in critically ill AKI patients. Monitoring serum magnesium and proper correction in critically ill patients with AKI should be considered an AKD preventive intervention in future trials.
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Affiliation(s)
- Supawadee Suppadungsuk
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA,
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand,
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Nasrin Nikravangolsefid
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Waryaam Singh
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Wisit Cheungpasitporn
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Yue Dong
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Kianoush B Kashani
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
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Renberg M, Hertzberg D, Rimes-Stigare C, Hallqvist L, Bell M. Advanced chronic kidney disease after surgery and the contribution of acute kidney disease: a national observational cohort study. Br J Anaesth 2024; 132:1238-1247. [PMID: 38553313 DOI: 10.1016/j.bja.2024.02.024] [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: 12/19/2023] [Revised: 01/23/2024] [Accepted: 02/21/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND Limited knowledge exists regarding long-term renal outcomes after noncardiac surgery. This study investigated the incidence of, and risk factors for, developing advanced chronic kidney disease (CKD) and major adverse kidney events within 1 yr of surgery in a nationwide cohort. METHODS Adults without renal dysfunction before noncardiac surgery in Sweden were included between 2007 and 2013 in this observational multicentre cohort study. We analysed data from a national surgical database linked to several national and quality outcome registries. Associations of perioperative risk factors with advanced CKD (estimated glomerular filtration rate [eGFR] <30 ml min-1 1.73 m-2) and major adverse kidney events within 1 yr (MAKE365, comprising eGFR <30 ml min-1 1.73 m-2, chronic dialysis, death) were quantified. RESULTS Of 237,124 patients, 1597 (0.67%) developed advanced CKD and 16,789 (7.1%) developed MAKE365. Risk factors for advanced CKD included higher ASA physical status, urological surgery, extended surgical duration, prolonged postoperative hospital stay, repeated surgery, and postoperative use of renin-angiotensin-aldosterone system blockers. Advanced acute kidney disease (AKD) (eGFR <30 ml min-1 1.73 m-2 within 90 postoperative days) occurred in 1661 (0.70%) patients and was associated with advanced CKD (subdistribution hazard ratio [SHR] 44.5, 95% confidence interval [CI] 38.7-51.1) and MAKE365 (hazard ratio [HR] 6.60, 95% CI 6.07-7.17). Among patients with advanced AKD after surgery 36% developed advanced CKD at 1 yr after surgery and 51% developed MAKE365. CONCLUSIONS Advanced CKD within 1 yr after surgery is uncommon but clinically important in patients without preoperative renal dysfunction. Advanced AKD after surgery constitutes a major risk factor for advanced CKD and MAKE365.
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Affiliation(s)
- Mårten Renberg
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
| | - Daniel Hertzberg
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Claire Rimes-Stigare
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Linn Hallqvist
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Max Bell
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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Li M, Han S, Liang F, Hu C, Zhang B, Hou Q, Zhao S. Machine Learning for Predicting Risk and Prognosis of Acute Kidney Disease in Critically Ill Elderly Patients During Hospitalization: Internet-Based and Interpretable Model Study. J Med Internet Res 2024; 26:e51354. [PMID: 38691403 PMCID: PMC11097053 DOI: 10.2196/51354] [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: 07/28/2023] [Revised: 01/23/2024] [Accepted: 04/17/2024] [Indexed: 05/03/2024] Open
Abstract
BACKGROUND Acute kidney disease (AKD) affects more than half of critically ill elderly patients with acute kidney injury (AKI), which leads to worse short-term outcomes. OBJECTIVE We aimed to establish 2 machine learning models to predict the risk and prognosis of AKD in the elderly and to deploy the models as online apps. METHODS Data on elderly patients with AKI (n=3542) and AKD (n=2661) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were used to develop 2 models for predicting the AKD risk and in-hospital mortality, respectively. Data collected from Xiangya Hospital of Central South University were for external validation. A bootstrap method was used for internal validation to obtain relatively stable results. We extracted the indicators within 24 hours of the first diagnosis of AKI and the fluctuation range of some indicators, namely delta (day 3 after AKI minus day 1), as features. Six machine learning algorithms were used for modeling; the area under the receiver operating characteristic curve (AUROC), decision curve analysis, and calibration curve for evaluating; Shapley additive explanation (SHAP) analysis for visually interpreting; and the Heroku platform for deploying the best-performing models as web-based apps. RESULTS For the model of predicting the risk of AKD in elderly patients with AKI during hospitalization, the Light Gradient Boosting Machine (LightGBM) showed the best overall performance in the training (AUROC=0.844, 95% CI 0.831-0.857), internal validation (AUROC=0.853, 95% CI 0.841-0.865), and external (AUROC=0.755, 95% CI 0.699-0.811) cohorts. In addition, LightGBM performed well for the AKD prognostic prediction in the training (AUROC=0.861, 95% CI 0.843-0.878), internal validation (AUROC=0.868, 95% CI 0.851-0.885), and external (AUROC=0.746, 95% CI 0.673-0.820) cohorts. The models deployed as online prediction apps allowed users to predict and provide feedback to submit new data for model iteration. In the importance ranking and correlation visualization of the model's top 10 influencing factors conducted based on the SHAP value, partial dependence plots revealed the optimal cutoff of some interventionable indicators. The top 5 factors predicting the risk of AKD were creatinine on day 3, sepsis, delta blood urea nitrogen (BUN), diastolic blood pressure (DBP), and heart rate, while the top 5 factors determining in-hospital mortality were age, BUN on day 1, vasopressor use, BUN on day 3, and partial pressure of carbon dioxide (PaCO2). CONCLUSIONS We developed and validated 2 online apps for predicting the risk of AKD and its prognostic mortality in elderly patients, respectively. The top 10 factors that influenced the AKD risk and mortality during hospitalization were identified and explained visually, which might provide useful applications for intelligent management and suggestions for future prospective research.
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Affiliation(s)
- Mingxia Li
- Department of Critical Care Medicine, Xiangya Hospital of Central South University, Changsha, China
- Department of Critical Care Medicine, ZhuJiang Hospital of Southern Medical University, Guangzhou, China
| | - Shuzhe Han
- Department of Obstetrics and Gynecology, 967th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Dalian, China
| | - Fang Liang
- Department of Hematology and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Chenghuan Hu
- Department of Critical Care Medicine, Xiangya Hospital of Central South University, Changsha, China
| | - Buyao Zhang
- Department of Critical Care Medicine, Xiangya Hospital of Central South University, Changsha, China
| | - Qinlan Hou
- Department of Critical Care Medicine, Xiangya Hospital of Central South University, Changsha, China
| | - Shuangping Zhao
- Department of Critical Care Medicine, Xiangya Hospital of Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Hunan Provincial Clinical Research Center of Intensive Care Medicine, Changsha, China
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12
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Koh ES, Chung S. Recent Update on Acute Kidney Injury-to-Chronic Kidney Disease Transition. Yonsei Med J 2024; 65:247-256. [PMID: 38653563 PMCID: PMC11045347 DOI: 10.3349/ymj.2023.0306] [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: 07/26/2023] [Revised: 12/27/2023] [Accepted: 01/23/2024] [Indexed: 04/25/2024] Open
Abstract
Acute kidney injury (AKI) is characterized by an abrupt decline of excretory kidney function. The incidence of AKI has increased in the past decades. Patients diagnosed with AKI often undergo diverse clinical trajectories, such as early or late recovery, relapses, and even a potential transition from AKI to chronic kidney disease (CKD). Although recent clinical studies have demonstrated a strong association between AKI and progression of CKD, our understanding of the complex relationship between AKI and CKD is still evolving. No cohort study has succeeded in painting a comprehensive picture of these multi-faceted pathways. To address this lack of understanding, the idea of acute kidney disease (AKD) has recently been proposed. This presents a new perspective to pinpoint a period of heightened vulnerability following AKI, during which a patient could witness a substantial decline in glomerular filtration rate, ultimately leading to CKD transition. Although AKI is included in a range of kidney conditions collectively known as AKD, spanning from mild and self-limiting to severe and persistent, AKD can also occur without a rapid onset usually seen in AKI, such as when kidney dysfunction slowly evolves. In the present review, we summarize the most recent findings about AKD, explore the current state of biomarker discovery related to AKD, discuss the latest insights into pathophysiological underpinnings of AKI to CKD transition, and reflect on therapeutic challenges and opportunities that lie ahead.
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Affiliation(s)
- Eun Sil Koh
- Division of Nephrology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sungjin Chung
- Division of Nephrology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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13
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Nishio H, Sakakibara Y, Ikuno T, Seki Y, Nishimura K. Impact of Recovery from Acute Kidney Injury After Aortic Arch Repair. Ann Thorac Surg 2023; 116:1205-1212. [PMID: 35654165 DOI: 10.1016/j.athoracsur.2022.05.021] [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: 10/01/2021] [Revised: 05/02/2022] [Accepted: 05/07/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND The impact of recovery from acute kidney injury (AKI) after open thoracic aortic surgery on follow-up outcomes is unclear. METHODS This retrospective study included 214 patients who underwent aortic arch surgery requiring hypothermic circulatory arrest between 2007 and 2019. Patients who required preoperative renal replacement therapy and patients who died within 7 postoperative days were excluded. The incidence of recovery from AKI was examined. Renal outcomes were compared among patients with no AKI (Group N), recovery from AKI (Group R), and persistent AKI (Group P). RESULTS Preoperative kidney function was similar among the 3 groups. Among the 115 patients who developed postoperative AKI, 80.9% recovered from AKI at discharge. The 5-year cumulative mortality rate was 18.0%, 24.5%, and 68.4% in Group N, R, and P, respectively (P < .001, Group R vs Group P). The 5-year cumulative incidence of renal replacement therapy dependency was 0.0%, 5.4%, and 22.7%, respectively (P = .04, Group N vs Group R; P = .01, Group R vs Group P). The medians (interquartile range) of estimated glomerular filtration rate (mL/min/1.73 m2) 2 years after surgery were 65.2 (50.4-80.2), 54.3 (41.4-65.9), and 56.9 (40.2-67.5), respectively (P = .03, Group N vs Group R). CONCLUSIONS The majority of patients recovered from AKI after thoracic aortic repair by discharge. However, the prolonged impact of AKI recovery on kidney function was observed during the follow-up period. Diligent follow-up after discharge is warranted for early identification of patients at high risk of kidney disease progression.
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Affiliation(s)
- Hiroomi Nishio
- Department of Cardiovascular Surgery, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan.
| | - Yutaka Sakakibara
- Department of Cardiovascular Surgery, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan
| | - Takeshi Ikuno
- Department of Cardiovascular Surgery, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan
| | - Yusuke Seki
- Department of Cardiovascular Surgery, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan
| | - Kazunobu Nishimura
- Department of Cardiovascular Surgery, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan
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14
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Kung CW, Chou YH. Acute kidney disease: an overview of the epidemiology, pathophysiology, and management. Kidney Res Clin Pract 2023; 42:686-699. [PMID: 37165615 DOI: 10.23876/j.krcp.23.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 02/20/2023] [Indexed: 05/12/2023] Open
Abstract
Acute kidney injury (AKI) increases the risk of chronic kidney disease (CKD), and AKI and CKD are seen as interconnected syndromes. Acute kidney disease (AKD) is defined as subacute damage and/or loss of kidney function occurring 7 to 90 days after AKI, during which period key interventions may be initiated to hinder the development of CKD. While AKD is usually under-recognized, it is associated with high morbidity and mortality globally. This review article aims to summarize the current knowledge concerning the epidemiology, pathophysiology, and management of AKD with the aim to develop monitoring strategies and therapeutic agents of AKD. Generally, AKD tends to occur more frequently in the elderly and those with chronic diseases, such as hypertension, diabetes mellitus, and metabolic syndrome. In addition, the severity, duration, and frequency of AKI are independent risk factors for AKD. Investigations of several mechanisms of AKD, such as renal tubular epithelium cell-cycle arrest, epigenetic change, chronic inflammation, mitochondria dysfunction, failed regeneration of tubular cells, metabolic reprogramming, and renin-angiotensin system (RAS) activation, have identified additional potential pharmacotherapy targets. Management of AKD includes prevention of repeated AKI, early and regular follow-up by a nephrologist, resumption and adjustment of essential medication, optimization of blood pressure control and nutrition management, and development of new pharmaceutical agents including RAS inhibitors. Finally, we outline a care bundle for AKD patients based on important lessons learned from studies and registries and identify the need for clinical trials of RAS inhibitors or other novel agents to impede ensuing CKD development.
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Affiliation(s)
- Chin-Wei Kung
- Department of Internal Medicine, China Medical University Hospital, China Medical University College of Medicine, Taichung, Taiwan
| | - Yu-Hsiang Chou
- Renal Division, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei City, Taiwan
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15
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Bendall AC, See EJ, Toussaint ND, Fazio T, Tan SJ. Community-acquired versus hospital-acquired acute kidney injury at a large Australian metropolitan quaternary referral centre: incidence, associations and outcomes. Intern Med J 2023; 53:1366-1375. [PMID: 35491485 DOI: 10.1111/imj.15787] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 04/06/2022] [Accepted: 04/18/2022] [Indexed: 08/22/2023]
Abstract
BACKGROUND There is increasing global incidence of acute kidney injury (AKI) and significant short- and long-term impacts on patients. AIMS To determine incidence and outcomes of community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) among inpatients in the Australian healthcare setting using modern health information systems. METHODS A retrospective cohort study of adult patients admitted to a quaternary hospital in Melbourne, Australia, between 1 January 2018 and 31 December 2019 utilising an electronic data warehouse. Participants included adult patients admitted for >24 h who had more than one serum creatinine level recorded during admission. Kidney transplant and maintenance dialysis patients were excluded. Main outcomes measured included AKI, as classified by the Kidney Disease Improving Global Outcomes (KDIGO) criteria, hospital length of stay and 30-day mortality. RESULTS A total of 6477 AKI episodes was identified across 43 791 admissions. Of all AKI episodes, 77% (n = 5011), 15% (n = 947) and 8% (n = 519) were KDIGO stage 1, 2 and 3 respectively. HA-AKI accounted for 55.9% episodes. Patients required intensive care unit admission in 22.7% (n = 1100) of CA-AKI and 19.3% (n = 935) of HA-AKI, compared with 7.5% (n = 2815) of patients with no AKI (P = 0.001). Patients with AKI were older with more co-morbidities, particularly chronic kidney disease (CKD). Length of stay was longer in CA-AKI (8.8 days) and HA-AKI (11.8 days) compared with admissions without AKI (4.9 days; P < 0.001). Thirty-day mortality was increased with CA-AKI (10.2%) and HA-AKI (12.8%) compared with no AKI (3.7%; P < 0.001). CONCLUSION The incidence of AKI detected by the electronic data warehouse was higher than previously reported. Patients who experienced AKI had greater morbidity and mortality. CKD was an important risk factor for AKI in hospitalised patients.
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Affiliation(s)
- Anna C Bendall
- Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Emily J See
- Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia
- Department of Critical Care, University of Melbourne, Melbourne, Victoria, Australia
| | - Nigel D Toussaint
- Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Department of Medicine (RMH), University of Melbourne, Melbourne, Victoria, Australia
| | - Timothy Fazio
- Department of Critical Care, University of Melbourne, Melbourne, Victoria, Australia
- Business Intelligence Unit, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Sven-Jean Tan
- Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Department of Medicine (RMH), University of Melbourne, Melbourne, Victoria, Australia
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16
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Murdeshwar A, Krishnamurthy S, Parameswaran N, Rajappa M, Deepthi B, Krishnasamy S, Ganapathy S, Karunakar P. Etiology and outcomes of acute kidney disease in children: a cohort study. Clin Exp Nephrol 2023; 27:548-556. [PMID: 36934196 DOI: 10.1007/s10157-023-02339-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 03/06/2023] [Indexed: 03/20/2023]
Abstract
BACKGROUND There is paucity of information regarding the etiology and outcomes of Acute Kidney Disease (AKD) in children. METHODS The objectives of this cohort study were to evaluate the etiology and outcomes of AKD; and analyze predictors of kidney survival (defined as free of CKD 2, 3a, 3b, 4 or 5). Patients aged 1 month to 18 years who developed AKD over a 4-year-period (January 2018-December 2021) were enrolled. Survivors were followed-up at the pediatric nephrology clinic, and screened for residual kidney injury. RESULTS Among 5710 children who developed AKI, 200 who developed AKD were enrolled. The median (IQR) eGFR was 17.03 (10.98, 28) mL/min/1.73 m2. Acute glomerulonephritis, acute tubular necrosis (ATN), hemolytic uremic syndrome (HUS), sepsis-associated AKD, and snake envenomation comprised of 69 (34.5%), 39 (19.5%), 24 (12%), 23 (11.5%) and 15 (7.5%) of the patients respectively. Overall, 88 (44%) children required kidney replacement therapy (KRT). There were 37 (18.5%) deaths within the AKD period. At a follow-up of 90 days, 32 (16%) progressed to chronic kidney disease stage-G2 or greater. At a median (IQR) follow-up of 24 (6, 36.5) months (n = 154), 27 (17.5%) had subnormal eGFR, and 20 (12.9%) had persistent proteinuria and/or hypertension. Requirement of KRT predicted kidney survival (free of CKD 2, 3a, 3b, 4 or 5) in AKD (HR 6.7, 95% CI 1.2, 46.4) (p 0.04). CONCLUSIONS Acute glomerulonephritis, ATN, HUS, sepsis-associated AKD and snake envenomation were common causes of AKD. Mortality in AKD was 18.5%, and 16% progressed to CKD-G2 or greater at 90-day follow-up.
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Affiliation(s)
- Amar Murdeshwar
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India
| | - Sriram Krishnamurthy
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India.
| | - Narayanan Parameswaran
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India
| | - Medha Rajappa
- Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India
| | - Bobbity Deepthi
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India
| | - Sudarsan Krishnasamy
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India
| | - Sachit Ganapathy
- Department of Biostatistics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India
| | - Pediredla Karunakar
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India
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Su CC, Chen JY, Chen SY, Shiao CC, Neyra JA, Matsuura R, Noiri E, See E, Chen YT, Hsu CK, Pan HC, Chang CH, Rosner MH, Wu VC. Outcomes associated with acute kidney disease: A systematic review and meta-analysis. EClinicalMedicine 2023; 55:101760. [PMID: 36531983 PMCID: PMC9755056 DOI: 10.1016/j.eclinm.2022.101760] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 11/08/2022] [Accepted: 11/09/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Acute kidney disease (AKD) defines the period after kidney damage and it is a critical period of both repair and fibrotic pathways. However, the outcomes of patients with AKD have not been well-defined. METHODS In this meta-analysis, PubMed, Embase, Cochrane and China National Knowledge Infrastructure were searched on July 31,2022. We excluded studies including patients undergoing kidney replacement therapy at enrollment. The data was used to conduct a random-effects model for pool outcomes between patients with AKD and non-AKD (NKD). This study is registered with PROSPERO, CRD 42021271773. FINDINGS The search generated 739 studies of which 21 studies were included involving 1,114,012 patients. The incidence rate of community-acquired AKD was 4.60%, 2.11% in hospital-acquired AKD without a prior AKI episode, and 26.11% in hospital-acquired AKD with a prior AKI episode. The all-cause mortality rate was higher in the AKD group (26.54%) than in the NKD group (7.78%) (odds ratio [OR]: 3.62, 95% confidence interval [CI]: 2.64 to 4.95, p < 0.001, I2 = 99.11%). The rate of progression to end-stage kidney disease (ESKD) was higher in the AKD group (1.3%) than in the NKD group (0.14%) (OR: 6.58, p < 0.001, I2 = 94.95%). The incident rate of CKD and progressive CKD was higher in the AKD group (37.2%) than in the NKD group (7.45%) (OR:4.22, p < 0.001, I2 = 96.67%). Compared to the NKD group, patients with AKD without prior AKI had a higher mortality rate (OR: 3.00, p < 0.001, I2 = 99.31%) and new-onset ESKD (OR:4.96, 95% CI, p = 0.002, I2 = 97.37%). INTERPRETATION AKD is common in community and hospitalized patients who suffer from AKI and also occurs in patients without prior AKI. The patients with AKD, also in those without prior AKI had a higher risk of mortality, and new-onset ESKD than the NKD group. FUNDING This study was supported by Ministry of Science and Technology (MOST) of the Republic of China (Taiwan) [grant number, MOST 107-2314-B-002-026-MY3, 108-2314-B-002-058, 110-2314-B-002-241, 110-2314-B-002-239], National Science and Technology Council (NSTC) [grant number, NSTC 109-2314-B-002-174-MY3, 110-2314-B-002-124-MY3, 111-2314-B-002-046, 111-2314-B-002-058], National Health Research Institutes [PH-102-SP-09], National Taiwan University Hospital [109-S4634, PC-1246, PC-1309, VN109-09, UN109-041, UN110-030, 111-FTN0011] Grant MOHW110-TDU-B-212-124005, Mrs. Hsiu-Chin Lee Kidney Research Fund and Chi-mei medical center CMFHR11136. JAN is supported, in part, by grants from the National Institute of Health, NIDDK (R01 DK128208 and P30 DK079337) and NHLBI (R01 HL148448-01).
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Affiliation(s)
- Ching-Chun Su
- Division of Nephrology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - 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
| | - Sheng-Yin Chen
- Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Chih-Chung Shiao
- Division of Nephrology, Department of Internal Medicine, Camillian Saint Mary's Hospital Luodong; and Saint Mary's Junior College of Medicine, Nursing and Management, Yilan, Taiwan
| | - Javier A. Neyra
- Department of Internal Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ryo Matsuura
- Department of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan
| | - Eisei Noiri
- National Center Biobank Network, National Center for Global Health and Medicine, Shinjuku, Japan
| | - Emily See
- Department of Nephrology, Royal Melbourne Hospital, Melbourne, Australia
- Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Australia
| | - Yih-Ting Chen
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Taiwan
| | - Cheng-Kai Hsu
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Taiwan
| | - Heng-Chih Pan
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Taiwan
| | - Chih-Hsiang Chang
- Division of Nephrology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Main Branch, Taoyuan City, Taiwan
| | - Mitchell H. Rosner
- Department of Medicine, University of Virginia Health System Charlottesville, VA, 22908, USA
| | - Vin-Cent Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Corresponding author. National Taiwan University Hospital, 7 Chung-Shan South Road, Zhong-Zheng District Taipei 100, Taiwan.
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18
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Agathis robusta Bark Extract Protects from Renal Ischemia-Reperfusion Injury: Phytochemical, In Silico and In Vivo Studies. Pharmaceuticals (Basel) 2022; 15:ph15101270. [PMID: 36297382 PMCID: PMC9610891 DOI: 10.3390/ph15101270] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 10/11/2022] [Accepted: 10/12/2022] [Indexed: 11/06/2022] Open
Abstract
Background: Acute kidney injury (AKI) induced by renal ischemia-reperfusion injury (RIRI) is associated with a high incidence of mortality. Existing therapies are mainly supportive, with no available nephroprotective agent. The purpose of this study is to examine the potential protective effect of Agathis robusta Bark Extract (ARBE) in RIRI. Methods: The chemical composition of ARBE was examined by LC-ESI-MS/MS. Network pharmacology was utilized to identify the RIRI molecular targets that could be aimed at by the identified major components of ARBE. Experimentally validated protein–protein interactions (PPIs) and compound-target networks were constructed using the STRING database and Cytoscape software. Molecular docking studies were employed to assess the interaction of the most relevant ARBE compounds with the hub RIRI-related targets. Furthermore, ARBE was tested in a rat model of RIRI. Results: The phytochemical analysis identified 95 components in ARBE, 37 of which were majors. Network analysis identified 312 molecular targets of RIRI that were associated with ARBE major compounds. Of these 312, the top targets in the experimentally validated PPI network were HSP90, EGFR, and P53. The most relevant compounds based on their peak area and network degree value included narcissoside, isorhamnetin-3-O-glucoside, and syringetin-3-O-glucoside, among others. Docking studies of the most relevant compounds revealed significant interactions with the top RIRI-related targets. In the in vivo RIRI experiments, pretreatment of ARBE improved kidney function and structural changes. ARBE reduced the renal expression of p-NfkB and cleaved caspase-3 by downregulating HSP90 and P53 in rats exposed to RIRI. Conclusion: Taken together, this study revealed the chemical composition of ARBE, depicted the interrelationship of the bioactive ingredients of ARBE with the RIRI-related molecular targets, and validated a nephroprotective effect of ARBE in RIRI.
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19
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Chen YW, Wu MY, Mao CH, Yeh YT, Chen TT, Liao CT, Zheng CM, Hsu YH, Cherng YG, Wu MS. Severe acute kidney disease is associated with worse kidney outcome among acute kidney injury patients. Sci Rep 2022; 12:6492. [PMID: 35444219 PMCID: PMC9021248 DOI: 10.1038/s41598-022-09599-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 03/09/2022] [Indexed: 11/19/2022] Open
Abstract
Acute kidney disease (AKD) comprises acute kidney injury (AKI). However, whether the AKD staging system has prognostic values among AKI patients with different baseline estimated glomerular filtration (eGFR) remains a controversial issue. Algorithm-based approach was applied to identify AKI occurrence and to define different AKD stages. Risk ratio for major adverse kidney events (MAKE), including (1) eGFR decline > 35% from baseline, (2) initiation of dialysis, (3) in-hospital mortality of different AKD subgroups were identified by multivariable logistic regression. Among the 4741 AKI patients identified from January 2015 to December 2018, AKD stages 1–3 after AKI was common (53% in the lower baseline eGFR group and 51% in the higher baseline eGFR group). In the logistic regression model adjusted for demographics and comorbidities at 1-year follow-up, AKD stages 1/2/3 (AKD stage 0 as reference group) were associated with higher risks of MAKE (AKD stage: odds ratio, 95% confidence interval [95% CI], AKD 1: 1.85, 1.56–2.19; AKD 2: 3.43, 2.85–4.12; AKD 3: 10.41, 8.68–12.49). Regardless of baseline eGFR, staging criteria for AKD identified AKI patients who were at higher risk of kidney function decline, dialysis and mortality. Post-AKI AKD patients with severer stage need intensified care and timely intervention.
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Affiliation(s)
- Yu-Wei Chen
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan.,Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
| | - Mei-Yi Wu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan.,TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.,Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.,Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Cheng-Hsien Mao
- Information Technology Office, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Yu-Ting Yeh
- Information Technology Office, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Tzu-Ting Chen
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.,Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan
| | - Chia-Te Liao
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan.,TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.,Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Cai-Mei Zheng
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan.,TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.,Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yung-Ho Hsu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan.,Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.,Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yih-Giun Cherng
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. .,Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
| | - Mai-Szu Wu
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng Road, Zhonghe District, New Taipei City, 235, Taiwan. .,Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. .,TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan. .,Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
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20
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Liu J, Li Q, Chen W, Huang H, Yu Y, Wang B, Liang G, Lai W, Liu L, Ying M, Wei H, Huang Z, Ni J, Chen J, Chen S, Liu Y. Incidence and mortality of acute kidney disease following coronary angiography: a cohort study of 9223 patients. Int Urol Nephrol 2022; 54:2433-2440. [PMID: 35235109 DOI: 10.1007/s11255-022-03110-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 11/22/2021] [Indexed: 12/22/2022]
Abstract
PURPOSE Acute kidney disease (AKD) is an important state in the evolving kidney diseases. However, there is limited data on the incidence and prognosis of AKD following coronary angiography (CAG). Therefore, we aim to characterize the incidence and prognosis of AKD across a large population of CAG patients. METHODS The consecutive patients with baseline and following measurement of serum creatinine (Scr) between 7 and 90 days after CAG procedure were included. The AKD was defined as a decrease in glomerular filtration rate by > 35%, or an increase in Scr of > 50% (from 7 to 90 days). Survival curves, univariate and multivariable cox regressions were used to assess the association between AKD and mortality. RESULTS Among 9223 patients (male, 60.3%, mean age, 61.7 ± 9.6), 1540 had AKD. During a median follow-up of 5.4 (IQR 2.2-8.6) years, 1562 (16.9%) patients died. The mortality among the patients with AKD was higher than the non-AKD group (24.8% vs. 15.4%, p < 0.001). AKD was independently associated with a significantly increased risk of all-cause mortality (adjusted hazard ratio [aHR], 1.57; 95% CI 1.39-1.78; p < 0.001). CONCLUSIONS Our study suggested that AKD is commonly observed after CAG and increased half mortality risk than those without AKD. More attention needs to be paid to patients suffering from AKD.
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Affiliation(s)
- Jin Liu
- Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, South China University of Technology, Guangzhou, 510080, China
| | - Qiang Li
- Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, South China University of Technology, Guangzhou, 510080, China
| | - Weihua Chen
- The Third Clinical Medical College, Fujian Medical University, Fuzhou, 350000, China
| | - Haozhang Huang
- Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, South China University of Technology, Guangzhou, 510080, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Yaren Yu
- Department of Cardiology, The First People's Hospital of Foshan, No.81 of Lingnan Road, Chancheng District, Foshan, 528000, Guangdong Province, China
| | - Bo Wang
- Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, South China University of Technology, Guangzhou, 510080, China
| | - Guoxiao Liang
- Guangdong Medical University, Dongguan, 524023, China
| | - Wenguang Lai
- Guangdong Provincial People's Hospital, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510515, China
| | - Liwei Liu
- Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, South China University of Technology, Guangzhou, 510080, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Ming Ying
- Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, South China University of Technology, Guangzhou, 510080, China
| | - Haiyan Wei
- The First People's Hospital of Kashgar Prefecture, Kashi, 844000, China
| | - Zhigang Huang
- Guangdong Medical University, Dongguan, 524023, China
| | - Jindong Ni
- Guangdong Medical University, Dongguan, 524023, China
| | - Jiyan Chen
- Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, South China University of Technology, Guangzhou, 510080, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
- Guangdong Provincial People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510100, China
| | - Shiqun Chen
- Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, South China University of Technology, Guangzhou, 510080, China.
| | - Yong Liu
- Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, South China University of Technology, Guangzhou, 510080, China.
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China.
- Guangdong Provincial People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510100, China.
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21
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Chen JJ, Lee TH, Kuo G, Yen CL, Chen SW, Chu PH, Fan PC, Chien-Chia Wu V, Chang CH. Acute Kidney Disease After Acute Decompensated Heart Failure. Kidney Int Rep 2022; 7:526-536. [PMID: 35257065 PMCID: PMC8897687 DOI: 10.1016/j.ekir.2021.12.033] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 12/09/2021] [Accepted: 12/28/2021] [Indexed: 11/26/2022] Open
Abstract
Introduction Acute kidney disease (AKD) represents a continuum of kidney injury for 7 to 90 days after acute kidney injury (AKI). The incidence and prognosis of AKD after acute decompensated heart failure (ADHF) are currently unclear. The aims of this study were to explore the incidence of AKD and the transition from AKI to AKD, to identify risk factors for AKD and develop a prediction model for any-stage AKD, and to evaluate the prognosis of AKD. Methods A total of 7519 patients admitted for ADHF between January 1, 2008, and December 31, 2018, from a multi-institutional database were identified. The composite outcomes after ADHF were stage 3 AKD and all-cause death. The prognosis impact of AKD, including major adverse kidney events (MAKEs), all-cause death, and heart failure hospitalization (HFH), during 5 years of follow-up was analyzed. Results The overall incidence of AKI and AKD after ADHF was 9% and 21.2%, respectively; 39.4% of the patients diagnosed with having AKI during ADHF subsequently developed AKD whereas 19.4% of the patients without an identified AKI episode subsequently developed AKD. The predictive scoring models revealed C-statistics of 0.726 (95% CI: 0.712–0.740) for any-stage AKD and 0.807 (95% CI: 0.793–0.821) for the composite of stage 3 AKD and death. Finally, AKD was associated with higher risks of all-cause death, MAKE, and HFH during the 5 years of follow-up (P < 0.001). Conclusion AKD after ADHF are associated with adverse outcomes. Our model could help in identification of patients at risk for AKD development, especially in those who did not have an index AKI episode.
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22
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Lameire NH, Levin A, Kellum JA, Cheung M, Jadoul M, Winkelmayer WC, Stevens PE. Harmonizing acute and chronic kidney disease definition and classification: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference. Kidney Int 2021; 100:516-526. [PMID: 34252450 DOI: 10.1016/j.kint.2021.06.028] [Citation(s) in RCA: 259] [Impact Index Per Article: 64.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 06/08/2021] [Accepted: 06/15/2021] [Indexed: 12/21/2022]
Abstract
Kidney disease is an important public health problem. Both acute kidney injury (AKI) and chronic kidney disease have been well defined and classified, leading to improved research efforts and subsequent management strategies and recommendations. For those patients with abnormalities in kidney function and/or structure who meet neither the definition of AKI nor chronic kidney disease, there remains a gap in research, care, and guidance. The term acute kidney diseases and disorders, abbreviated to acute kidney disease (AKD), has been introduced as an important construct to address this. To expand and harmonize existing definitions and to ultimately better inform research and clinical care, Kidney Disease: Improving Global Outcomes (KDIGO) organized a consensus workshop. Multiple invitees from around the globe, representing both acute and chronic kidney disease researchers and experts, met virtually to examine existing data, and discuss key concepts related to AKD. Despite some remaining unresolved questions, conference attendees reached general consensus on the definition and classification of AKD, management strategies, and research priorities. AKD is defined by abnormalities of kidney function and/or structure with implications for health and with a duration of ≤3 months. AKD may include AKI, but, more importantly, also includes abnormalities in kidney function that are not as severe as AKI or that develop over a period of >7 days. The cause(s) of AKD should be sought, and classification includes functional and structural parameters. Management of AKD is currently based on empirical considerations. A robust research agenda to enable refinement and validation of definitions and classification systems, and thus testing of interventions and strategies, is proposed.
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Affiliation(s)
- Norbert H Lameire
- Renal Division, Department of Medicine, University Hospital Ghent, Ghent, Belgium.
| | - Adeera Levin
- Division of Nephrology, The University of British Columbia, Vancouver, British Columbia, Canada
| | - John A Kellum
- Department of Critical Care Medicine, Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | | | - Michel Jadoul
- Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Wolfgang C Winkelmayer
- Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Paul E Stevens
- Kent Kidney Care Centre, East Kent Hospitals University NHS Foundation Trust, Canterbury, UK.
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