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Puspitasari HA, Hidayati EL, Fahlevi R, Yuniar I, Pardede SO, Aryadevi NNB. Pediatric continuous kidney replacement therapy: The Indonesian experience. Pediatr Nephrol 2025:10.1007/s00467-025-06807-0. [PMID: 40404988 DOI: 10.1007/s00467-025-06807-0] [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: 11/02/2024] [Revised: 04/28/2025] [Accepted: 04/28/2025] [Indexed: 05/24/2025]
Abstract
BACKGROUND Acute kidney injury (AKI) is a common complication in critically ill children, with continuous kidney replacement therapy (CKRT) as the key treatment, especially for hemodynamically unstable children. Although numerous studies have been conducted on CKRT, data from resource-constrained settings are scarce. Centers with more experience in CKRT tend to have better survival rates. This study aims to describe and analyze the characteristics of critically ill patients who received CKRT and examine the factors influencing CKRT outcomes in resource-limited settings. METHODS A retrospective analysis was conducted on medical records from January 2015 to June 2023. Demographic data; clinical and laboratory profiles; hospitalization duration; use of inotropic support and mechanical ventilation; and the presence of sepsis, AKI, acute lung injury, acute respiratory distress syndrome, and encephalopathy were recorded and compared between survivors and non-survivors. RESULTS Fifty-six critically ill children underwent CKRT. The median age was 7.4 years, and the median body weight was 22.2 kg. CKRT was mostly indicated in sepsis-associated AKI (41.1%), nonsepsis AKI (23.2%), and acute-on-chronic kidney disease (21.4%). The median CKRT duration was 52.2 h, with median total delivered dose and mean blood flow rate per kilogram of 22.2 and 3.1 mL/kg/min, respectively. The overall survival rate was 25%. CONCLUSIONS Although patient demographics and CKRT prescriptions were like those at other centers, survival was low at our center because of considerable resource limitations. Despite challenges, CKRT remains the preferred treatment for critically ill children.
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Affiliation(s)
- Henny Adriani Puspitasari
- Department of Child Health, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia.
| | - Eka Laksmi Hidayati
- Department of Child Health, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Reza Fahlevi
- Department of Child Health, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Irene Yuniar
- Department of Child Health, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Sudung O Pardede
- Department of Child Health, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
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Ouyang X, Fu M, Li J, Gao J, Xu L, Pei Y, Jiang X. Risk factors for occurrence and death of sepsis-associated acute kidney injury in children with sepsis. Int Immunopharmacol 2024; 143:113551. [PMID: 39488919 DOI: 10.1016/j.intimp.2024.113551] [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: 06/12/2024] [Revised: 10/21/2024] [Accepted: 10/30/2024] [Indexed: 11/05/2024]
Abstract
INTRODUCTION The 28th Acute Disease Quality Initiative (ADQI) Workgroup proposed the first international consensus on definition of SA-AKI in June 2023. The incidence and mortality of ADQI-defined SA-AKI in septic children is unknown, and the risk factors for the occurrence and death of SA-AKI is unexplored. METHODS We conducted a retrospective study of septic children between January 1, 2018 and December 31, 2022. Logistic regression analysis was used to identify risk factors for SA-AKI. COX proportional hazards regression analysis was utilized for analyzing the risk factors for 30-day mortality in SA-AKI and septic children. RESULTS 221 children were included, of which 81 (36.7 %) developed SA-AKI, with 25.9 % developed into acute kidney disease. Older age, lower baseline eGFR and mechanical ventilation were independently associated with SA-AKI (P < 0.001, P < 0.01 and P < 0.05 respectively). Among the 81 SA-AKI children, 32.1 % died within 30 days from sepsis diagnosis, with higher mortality in children with late SA-AKI than early SA-AKI (72.2 % versus 20.6 %, P < 0.001). Septic shock was independently associated with 30-day death in SA-AKI children (P < 0.05). The overall 30-day mortality of septic children was 19.0 %, with mechanical ventilation, SA-AKI, and septic shock identified as independently associated with 30-day death (P < 0.001, P < 0.05 and P < 0.001 respectively). CONCLUSIONS SA-AKI is of high incidence and mortality in septic children. Older age, lower baseline eGFR and mechanical ventilation were independent risk factors for SA-AKI. SA-AKI was independently associated with 30-day mortality in septic children.
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Affiliation(s)
- Xiaojun Ouyang
- Department of Pediatric Nephrology and Rheumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Meng Fu
- Department of Pediatric Nephrology and Rheumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jie Li
- Department of Pediatric Nephrology and Rheumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jie Gao
- Department of Pediatric Nephrology and Rheumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Lingling Xu
- Department of Pediatric Nephrology and Rheumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
| | - Yuxin Pei
- Department of Pediatric Nephrology and Rheumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
| | - Xiaoyun Jiang
- Department of Pediatric Nephrology and Rheumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
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Xu J, Chen J, Li M, Jiang Z, Fang F, Hu J, Zhou Y, Li H, Bai Z, Li X, Lu G, Li Y. Utility of plasma suPAR to identify AKI and sepsis associated AKI in critically ill children. iScience 2024; 27:111247. [PMID: 39569376 PMCID: PMC11576388 DOI: 10.1016/j.isci.2024.111247] [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: 07/22/2024] [Revised: 09/09/2024] [Accepted: 10/22/2024] [Indexed: 11/22/2024] Open
Abstract
Current biomarkers for sepsis-associated acute kidney injury (SA-AKI) lack specificity. The role of soluble urokinase plasminogen activator receptor (suPAR) in discriminating AKI and SA-AKI in children remains elusive. This prospective multicenter study was conducted in critically ill children cohorts using a derivation-validation design, and plasma samples were collected within first 24 h after admission. Plasma suPAR was independently associated with AKI, SA-AKI, and PICU mortality, even after adjustment for confounding variables. This multiclass classification model had the micro-average AUC of 0.89 with specificity of 97.6% for discriminating non-septic AKI, and specificity of 99.0% for discriminating SA-AKI, based on the cut-off values of 1.5 and 2.3-fold baseline in serum creatinine (SCr) and 4.5 and 11.2 ng/mL in plasma suPAR. The multiclass classification model provides the cutoffs for plasma suPAR and SCr and specifically discriminates critically ill children at high risk of non-septic AKI and SA-AKI, which can facilitate clinical utility.
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Affiliation(s)
- Jing Xu
- Department of Nephrology and Immunology, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China
| | - Jiao Chen
- Pediatric Intensive Care Unit, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China
- Pediatric Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, P.R. China
| | - Min Li
- Pediatric Intensive Care Unit, Anhui Provincial Children's Hospital, Hefei, Anhui Province, P.R. China
| | - Zhen Jiang
- Pediatric Intensive Care Unit, Xuzhou Children's Hospital, Xuzhou, Jiangsu Province, P.R. China
| | - Fang Fang
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China
| | - Junlong Hu
- Department of Nephrology and Immunology, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China
| | - Yueying Zhou
- Department of Nephrology and Immunology, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China
| | - Huiwen Li
- Department of Nephrology and Immunology, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China
| | - Zhenjiang Bai
- Pediatric Intensive Care Unit, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China
| | - Xiaozhong Li
- Department of Nephrology and Immunology, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China
| | - Guoping Lu
- Pediatric Intensive Care Unit, Children's Hospital of Fudan University, Shanghai, P.R. China
| | - Yanhong Li
- Department of Nephrology and Immunology, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China
- Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China
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Hakim DDL, Widiasta A, Sari CA, Martiano MR. Inferior vena cava-aortic ratio measurement as a promising modality in assessing intravascular volume in children with sepsis. Pediatr Nephrol 2024; 39:3339-3346. [PMID: 38977444 DOI: 10.1007/s00467-024-06446-x] [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: 03/26/2024] [Revised: 06/11/2024] [Accepted: 06/18/2024] [Indexed: 07/10/2024]
Abstract
BACKGROUND Hemodynamic monitoring is crucial for the comprehensive management of children with sepsis, particularly those involving the kidneys. Sepsis-associated acute kidney injury (S-AKI) is closely linked to poor outcomes. Recently, ultrasonography modalities have been widely accepted as a non-invasive, rapid, and reliable tool for assessing volume status. We conducted research to determine intravascular volume based on ultrasound examination in S-AKI patients. METHODS A prospective cohort study was conducted between December 2023 and March 2024 in the Pediatric Intensive Care Unit (PICU) at Hasan Sadikin General Hospital. We divided the patients into two groups: those with sepsis without AKI and those with S-AKI. The intravascular volume was measured by the IVC/Ao (inferior vena cava/abdominal aorta) ratio using two-dimensional ultrasonography and USCOM before and 24 h after fluid treatment. The results were analyzed using SPSS 25, with a significance level of p < 0.05. RESULTS A total of 36 pediatric patients (aged 1 month-18 years) with sepsis were included. The IVC/Ao ratio before and after the fluid intervention demonstrated significant differences between the two groups (p < 0.001). USCOM Cardiac Index (CI) before and after the intervention also showed significant differences between the two groups (p < 0.001). Patients with S-AKI exhibited a poor hemodynamic response in the IVC/Ao ratio two-dimensional ultrasonography and USCOM examination. CONCLUSIONS IVC/Ao ratio measurement is as accurate as USCOM and can be used as a simple and cost-effective alternative for hemodynamic monitoring.
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Affiliation(s)
| | - Ahmedz Widiasta
- Department of Child Health, Dr. Hasan Sadikin General Hospital-Universitas Padjadjaran, Bandung, Indonesia
| | - Chindy Arya Sari
- Department of Child Health, Dr. Hasan Sadikin General Hospital-Universitas Padjadjaran, Bandung, Indonesia
| | - Muhamad Rinaldhi Martiano
- Department of Child Health, Dr. Hasan Sadikin General Hospital-Universitas Padjadjaran, Bandung, Indonesia
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Ogorevc N, Slak P, Nikšić S, Novljan G, Fister P, Plut D. Contrast-Enhanced Ultrasound (CEUS) and Ultra-Microangiography (UMA) in Critically Ill Children with Acute Kidney Injury. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1205. [PMID: 39457170 PMCID: PMC11506883 DOI: 10.3390/children11101205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 09/28/2024] [Accepted: 09/29/2024] [Indexed: 10/28/2024]
Abstract
Acute kidney injury (AKI) is an acute condition of impaired kidney function with decreased glomerular filtration rate, which results in dysregulation in volume, electrolyte, and acid-base equilibrium. AKI can be a life-threatening condition and can also lead to chronic kidney disease. It is important to diagnose AKI early in the course of the disease or to predict its development, as this can influence therapeutic decisions, outcome, and, consequently, the prognosis. In clinical practice, an elevated serum creatinine concentration remains the most common laboratory indicator for diagnosing AKI. However, due to the delay in its rise, creatinine levels are often insensitive and inaccurate for early diagnosis. Novel biomarkers of kidney tubular injury and the renal angina index have shown promise in predicting AKI earlier and more accurately. Contrast-enhanced ultrasonography (CEUS) and ultra-microangiography (UMA) are radiological methods that can quantify renal microperfusion and may be able to predict the development of AKI. They have not yet been used for quantifying renal perfusion in children with risk factors for developing AKI. Further research is needed to compare these sonographic techniques with the renal angina index and emerging kidney injury biomarkers for predicting acute kidney injury (AKI) in both children and adults.
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Affiliation(s)
- Nace Ogorevc
- Clinical Radiology Institute, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; (P.S.); (D.P.)
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Peter Slak
- Clinical Radiology Institute, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; (P.S.); (D.P.)
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Stevan Nikšić
- Clinical Radiology Institute, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; (P.S.); (D.P.)
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Gregor Novljan
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Pediatric Nephrology Department, Children’s Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| | - Petja Fister
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Department of Pediatric Intensive Care, Children’s Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| | - Domen Plut
- Clinical Radiology Institute, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; (P.S.); (D.P.)
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
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Wang GB, Zhang XF, Liang B, Lei J, Xue J. Improving treatment plan and mental health in children with abdominal infection for broad-spectrum bacterial infections. World J Psychiatry 2024; 14:1319-1325. [PMID: 39319226 PMCID: PMC11417647 DOI: 10.5498/wjp.v14.i9.1319] [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: 07/24/2024] [Revised: 08/14/2024] [Accepted: 08/15/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Pediatric abdominal infection is a common but serious disease that requires timely and effective treatment. In surgical treatment, accurate diagnosis and rational application of antibiotics are the keys to improving treatment effects. AIM To investigate the effect of broad-spectrum bacterial detection on postoperative antibiotic therapy. METHODS A total of 100 children with abdominal infection who received surgical treatment in our hospital from September 2020 to July 2021 were grouped. The observation group collected blood samples upon admission and sent them for broad-spectrum bacterial infection nucleic acid testing, and collected pus or exudate during the operation for bacterial culture and drug sensitivity testing; the control group only sent bacterial culture and drug sensitivity testing during the operation. RESULTS White blood cell count, C-reactive protein, procalcitonin, 3 days after surgery, showed better postoperative index than the control group (P < 0.05). The hospital stay in the observation group was significantly shorter than that in the control group. The hospitalization cost in the observation group was significantly lower than that in the control group, and the difference between the two groups was statistically significant (P < 0.05). CONCLUSION Early detection of broad-spectrum bacterial infection nucleic acids in pediatric abdominal infections can help identify pathogens sooner and guide the appropriate use of antibiotics, improving treatment outcomes and reducing medical costs to some extent.
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Affiliation(s)
- Gui-Bo Wang
- Department of Pediatric Surgery, the First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei Province, China
| | - Xue-Feng Zhang
- Department of Pediatric Surgery, the First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei Province, China
| | - Bing Liang
- Department of Pediatric Surgery, the First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei Province, China
| | - Jie Lei
- Department of Pediatric Surgery, the First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei Province, China
| | - Jun Xue
- Department of General Surgery, the First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei Province, China
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Jiajun W, Kaifeng G, Jing Z. Urinary PKM2, a marker predicating acute kidney injury in patients with sepsis. Int Urol Nephrol 2024; 56:3039-3045. [PMID: 38635124 DOI: 10.1007/s11255-024-04054-0] [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: 01/30/2024] [Accepted: 04/09/2024] [Indexed: 04/19/2024]
Abstract
PURPOSE Acute kidney injury (AKI) is a complication commonly occurred in patients with sepsis, and AKI has become the leading cause associated with mortality. PKM2, as a rate-limiting enzyme of glycolysis, was considered to be involved in AKI in vitro and animal models. However, there have been no studies reported on the expression of PKM2 in humans and its association with AKI. METHODS A retrospective study including 57 patients (35 males and 22 females) that were admitted into hospital in 2019 was carried out in our research. The basic characteristics and clinical parameters of each patient were collected from patients' medical records. We assessed changes in the expression of serum and urinary PKM2 using ELISA and its association with clinical manifestations in patients with sepsis through correlation analysis. Besides, ROC analysis was applied for evaluating the role of PKM2 in predicting AKI and death rate. RESULTS Urinary PKM2 is obviously increased in patients with sepsis-associated AKI (P < 0.05), while no significant change was found in the expression of serum PKM2. Moreover, the expression of urinary PKM2 is positively correlated with serum creatinine (r=0.577, P < 0.01) and blood-urea-nitrogen (r=0.531, P<0.01). In addition, it is negatively correlated with glomerular filtration rate (r=-0.583, P<0.01). Besides, ROC analysis indicated that urinary PKM2 could be a predictor of AKI in patients with sepsis (AUC-ROC, 0.819; SE, 0.086, P = 0.004, 95% CI 0.651-0.986). CONCLUSIONS Urinary PKM2 could be a marker predicting acute kidney injury in patients with sepsis.
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Affiliation(s)
- Wu Jiajun
- Department of Emergency, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guo Kaifeng
- Department of Endocrinology and Metabolism, Minhang Hospital, Fudan University, Shanghai, China
| | - Zhou Jing
- Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 HaiNing Road, Shanghai, 200080, China.
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Khatana J, Thavamani A, Umapathi KK, Sankararaman S, Roy A. Increasing incidence of acute kidney injury in pediatric severe sepsis and related adverse hospital outcomes. Pediatr Nephrol 2023; 38:2809-2815. [PMID: 36622440 DOI: 10.1007/00467-022-05866-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 12/15/2022] [Accepted: 12/16/2022] [Indexed: 05/07/2023]
Abstract
BACKGROUND Pediatric severe sepsis (PSS) is associated with increased mortality, and acute kidney injury (AKI) is an independent risk factor of mortality in PSS. However, there is little data on impact of AKI on hospital outcomes in PSS. METHODS We analyzed non-overlapping years of the Kids' Inpatient Database (KID) and National Inpatient Sample (NIS) database between 2003 and 2019 of all pediatric patients with severe sepsis between 1 and 18 years of age. Using ICD diagnosis codes, patients were divided into two groups based on AKI status and compared for outcomes measures including in-hospital mortality and healthcare resource utilization using length of stay and inflation-adjusted hospitalization charges. RESULTS We analyzed 192,712 hospitalizations due to PSS during the 17-year period. Prevalence of AKI was 23.6% with overall increasing trend, P<0.001. Prevalence of AKI was significantly increased in patients with diabetes mellitus, organ transplantation, HIV, urinary tract anomalies, and malnutrition, P<0.001. Mortality rate was significantly higher among patients with AKI (19.8% vs. 8.1%, P<0.001). PSS with AKI had significantly higher median length of stay (14 vs. 11 days) and total hospitalization charges ($168,106 vs. 100,906), P<0.001. Multivariate logistic regression analysis showed that AKI without kidney replacement therapy (KRT) was associated with 3.02 times increased odds of mortality (95% CI 2.99-3.17, P<0.001) and those requiring KRT had 6.4 times increased odds of mortality (95%CI 6.1-6.7, P<0.001). AKI without KRT was associated with 7.7 (95% CI 7.3-8.05) additional days of hospitalization and 154,536 (95% CI 149,500-159,572) additional US dollars in hospitalization charges. CONCLUSION Almost 1 in 4 hospitalizations with PSS had AKI and was associated with >3 times increased risk of mortality and need for KRT further adversely impacts mortality and healthcare utilization. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Jasmine Khatana
- Department of Pediatrics, Metro Health Medical Center, Case Western Reserve University, Cleveland, USA
| | - Aravind Thavamani
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition Department of Pediatrics, UH Rainbow Babies and Children's Hospital/Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44106, USA.
| | | | - Senthilkumar Sankararaman
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition Department of Pediatrics, UH Rainbow Babies and Children's Hospital/Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44106, USA
| | - Aparna Roy
- Department of Pediatrics, Metro Health Medical Center, Case Western Reserve University, Cleveland, USA
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Khatana J, Thavamani A, Umapathi KK, Sankararaman S, Roy A. Increasing incidence of acute kidney injury in pediatric severe sepsis and related adverse hospital outcomes. Pediatr Nephrol 2023; 38:2809-2815. [PMID: 36622440 DOI: 10.1007/s00467-022-05866-x] [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: 09/01/2022] [Revised: 12/15/2022] [Accepted: 12/16/2022] [Indexed: 01/10/2023]
Abstract
BACKGROUND Pediatric severe sepsis (PSS) is associated with increased mortality, and acute kidney injury (AKI) is an independent risk factor of mortality in PSS. However, there is little data on impact of AKI on hospital outcomes in PSS. METHODS We analyzed non-overlapping years of the Kids' Inpatient Database (KID) and National Inpatient Sample (NIS) database between 2003 and 2019 of all pediatric patients with severe sepsis between 1 and 18 years of age. Using ICD diagnosis codes, patients were divided into two groups based on AKI status and compared for outcomes measures including in-hospital mortality and healthcare resource utilization using length of stay and inflation-adjusted hospitalization charges. RESULTS We analyzed 192,712 hospitalizations due to PSS during the 17-year period. Prevalence of AKI was 23.6% with overall increasing trend, P<0.001. Prevalence of AKI was significantly increased in patients with diabetes mellitus, organ transplantation, HIV, urinary tract anomalies, and malnutrition, P<0.001. Mortality rate was significantly higher among patients with AKI (19.8% vs. 8.1%, P<0.001). PSS with AKI had significantly higher median length of stay (14 vs. 11 days) and total hospitalization charges ($168,106 vs. 100,906), P<0.001. Multivariate logistic regression analysis showed that AKI without kidney replacement therapy (KRT) was associated with 3.02 times increased odds of mortality (95% CI 2.99-3.17, P<0.001) and those requiring KRT had 6.4 times increased odds of mortality (95%CI 6.1-6.7, P<0.001). AKI without KRT was associated with 7.7 (95% CI 7.3-8.05) additional days of hospitalization and 154,536 (95% CI 149,500-159,572) additional US dollars in hospitalization charges. CONCLUSION Almost 1 in 4 hospitalizations with PSS had AKI and was associated with >3 times increased risk of mortality and need for KRT further adversely impacts mortality and healthcare utilization. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Jasmine Khatana
- Department of Pediatrics, Metro Health Medical Center, Case Western Reserve University, Cleveland, USA
| | - Aravind Thavamani
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition Department of Pediatrics, UH Rainbow Babies and Children's Hospital/Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44106, USA.
| | | | - Senthilkumar Sankararaman
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition Department of Pediatrics, UH Rainbow Babies and Children's Hospital/Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44106, USA
| | - Aparna Roy
- Department of Pediatrics, Metro Health Medical Center, Case Western Reserve University, Cleveland, USA
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Raina M, Ashraf A, Soundararajan A, Mandal AK, Sethi SK. Pharmacokinetics in Critically Ill Children with Acute Kidney Injury. Paediatr Drugs 2023:10.1007/s40272-023-00572-z. [PMID: 37266815 DOI: 10.1007/s40272-023-00572-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/12/2023] [Indexed: 06/03/2023]
Abstract
Acute kidney injury (AKI) is a commonly encountered comorbidity in critically ill children. The coexistence of AKI disturbs drug pharmacokinetics and pharmacodynamics, leading to clinically significant consequences. This can complicate an already critical clinical scenario by causing potential underdosing or overdosing giving way to possible therapeutic failures and adverse reactions. Current available studies offer little guidance to help maneuver such complex dosing regimens and decision-making in pediatric patients as most of them are done on heterogeneous groups of adult populations. Though there are some studies on drug dosing during continuous renal replacement therapy (CRRT), their utility is in question because of the recent advances in CRRT technology. Our review aims to discuss the principles of pharmacokinetics pertinent for honing the existing practices of drug dosing in critically ill children with AKI, and the various complexities and intricate challenges involved. This in turn will provide a framework to help enable caretakers to tailor dosing regimens in complex clinical setups with further ease and precision.
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Affiliation(s)
| | - Amani Ashraf
- Northeast Ohio Medical University, Rootstown, OH, USA
| | - Anvitha Soundararajan
- Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA
| | | | - Sidharth Kumar Sethi
- Pediatric Nephrology, Kidney Institute, Medanta, The Medicity Hospital, Gurgaon, Haryana, 122001, India.
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Hui WF, Chan VPY, Cheung WL, Ku SW, Hon KL. Risk factors for development of acute kidney injury and acute kidney disease in critically ill children. J Nephrol 2023; 36:1425-1434. [PMID: 37060439 DOI: 10.1007/s40620-023-01613-z] [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: 07/26/2022] [Accepted: 02/23/2023] [Indexed: 04/16/2023]
Abstract
BACKGROUND Acute kidney injury (AKI) is common among critically ill children and these children are at risk of developing acute kidney disease (AKD). METHODS A prospective cohort study was conducted on children aged > 1 month to ≤ 18 years old admitted to the pediatric intensive care unit (ICU) of Hong Kong Children's Hospital from 6/2020 to 6/2021. The incidences and risk factors of both AKI and AKD were determined. RESULTS There were 254 eligible admissions (58.3% in males, with a median age of 4.9 [9.7] years). The overall AKI incidence was 41.7% and 56% of children who remained hospitalized in the pediatric ICU for ≥ 7 days after acquiring AKI developed AKD. Cardiac surgery, bone marrow transplantation and requirement of inotropes were risk factors for both AKI and AKD. The requirement of non-invasive ventilation [relative risk (RR): 2.625 (1.361, 5.064)], total medication dose [RR 1.006 (1.002, 1.010)] and maximal medication intensity [RR 1.154 (1.038, 1.283)] were additional determinants of AKI. Factors indicating more severe AKI and AKI progression were predictive of AKD development. The overall mortality in the pediatric ICU was 3.1%. AKI was significantly associated with mortality (p < 0.001), longer length of hospitalization in the pediatric ICU (p < 0.001) and hospital stay (p < 0.001). AKD was associated with a lower estimated glomerular filtration rate at discharge from the pediatric ICU (p = 0.036). CONCLUSION AKI and AKD were common among critically ill children, and were associated with significant morbidity and mortality. Few modifiable risk factors, especially those related to nephrotoxic medication exposure, were associated with AKI development and AKD progression.
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Affiliation(s)
- Wun Fung Hui
- Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Doctor's Office, 9/F, Tower B, 1 Shing Cheong Road, Kowloon Bay, Kowloon, Hong Kong.
| | - Vivian Pui Ying Chan
- Department of Pharmacy, Hong Kong Children's Hospital, G/F, Tower B, 1 Shing Cheong Road, Kowloon Bay, Kowloon, Hong Kong
| | - Wing Lum Cheung
- Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Doctor's Office, 9/F, Tower B, 1 Shing Cheong Road, Kowloon Bay, Kowloon, Hong Kong
| | - Shu Wing Ku
- Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Doctor's Office, 9/F, Tower B, 1 Shing Cheong Road, Kowloon Bay, Kowloon, Hong Kong
| | - Kam Lun Hon
- Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Doctor's Office, 9/F, Tower B, 1 Shing Cheong Road, Kowloon Bay, Kowloon, Hong Kong
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12
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Ozkaya PY, Taner S, Ersayoğlu I, Turan B, Yildirim Arslan S, Karapinar B, Kaplan Bulut I. Sepsis associated acute kidney injury in pediatric intensive care unit. Ther Apher Dial 2023; 27:73-82. [PMID: 36101487 DOI: 10.1111/1744-9987.13928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 08/28/2022] [Accepted: 09/08/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND We aimed to compare the acute kidney injury (AKI) incidence in pediatric septic shock patients according to the three different classifications. METHODS We analyzed retrospectively 52 patients with severe sepsis between January 2019 and December 2019. RESULTS While 21 patients have been diagnosed with SA-AKI according to the pRIFLE criteria, 20 children have been diagnosed according to the AKIN criteria, and 21 children have been diagnosed according to the KDIGO criteria. Older age, lower platelet count were determined as independently risk factor for SA-AKI. Older age and higher PRISM score were associated with mortality. According to Canonical correlation coefficients, pRIFLE is the most successful classification to distinguish AKI state. The canonical correlation coefficients for pRIFLE, KDIGO, and AKIN were 0.817, 0.648, and 0.615, respectively. CONCLUSION Although AKI incidence was similar between the three classifications, pRIFLE was the most successful classification to distinguish AKI state.
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Affiliation(s)
- Pinar Yazici Ozkaya
- Department of Pediatrics, Division of Pediatric Intensive Care, Ege University, School of Medicine, Izmir, Turkey
| | - Sevgin Taner
- Department of Pediatrics, Division of Pediatric Nephrology, Ege University, School of Medicine, Izmir, Turkey
| | - Irem Ersayoğlu
- Department of Pediatrics, Division of Pediatric Intensive Care, Ege University, School of Medicine, Izmir, Turkey
| | - Benay Turan
- Department of Pediatrics, Ege University, School of Medicine, Izmir, Turkey
| | - Sema Yildirim Arslan
- Department of Pediatrics, Division of Pediatric Nephrology, Ege University, School of Medicine, Izmir, Turkey
| | - Bülent Karapinar
- Department of Pediatrics, Division of Pediatric Intensive Care, Ege University, School of Medicine, Izmir, Turkey
| | - Ipek Kaplan Bulut
- Department of Pediatrics, Division of Pediatric Nephrology, Ege University, School of Medicine, Izmir, Turkey
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13
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Cui Y, Fang X, Li J, Deng L. Evaluation of neonatal acute kidney injury (AKI) after emergency gastrointestinal surgery. Asian J Surg 2022; 46:1924-1930. [PMID: 36089435 DOI: 10.1016/j.asjsur.2022.08.086] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/23/2022] [Accepted: 08/24/2022] [Indexed: 11/02/2022] Open
Abstract
BACKGROUND The overall incidence of acute kidney injury (AKI) in neonates undergoing emergency gastrointestinal surgery is yet to be determined. The study aims are to analyze our experience in emergency gastrointestinal surgery for neonates and to evaluate the incidence of AKI. METHODS We conducted a retrospective study of neonates undergoing emergency gastrointestinal surgery between June 31, 2018 and May 10, 2022 (N = 329). The primary outcome was the overall incidence of AKI. The diagnostic AKI was based on the Modified Kidney Disease: Improving Global Outcomes (KDIGO) definition of neonatal AKI. The secondary outcomes, including the postoperative length of hospital stay (PLOS), 24-h mortality, in-hospital mortality, and total in-hospital cost, were analyzed. The risk factors associated with the development of postoperative AKI were also analyzed. RESULTS The incidence of postoperative AKI was 9.1% (30/329). No significant differences were detected in the 24-h mortality and in-hospital mortality between the two cohorts. In the final model, patients undergoing mechanical ventilation before surgery, vasopressor support, surgical duration, intraoperative oliguria and preoperative lowest serum creatinine (SCr), were independently associated with AKI. CONCLUSION Our study found that patients undergoing mechanical ventilation before surgery, vasopressor support, surgical duration, intraoperative oliguria and preoperative lowest SCr were independently associated with postoperative AKI in neonates who accepted emergency gastrointestinal surgeries.
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Affiliation(s)
- Yu Cui
- Department of Anesthesiology, The Affiliated Hospital, School of Medicine, UESTC Chengdu Women's & Children's Central Hospital, Chengdu, 610091, China.
| | - Xing Fang
- Department of Information, The Affiliated Hospital, School of Medicine, UESTC Chengdu Women's & Children's Central Hospital, Chengdu, 610091, China
| | - Jia Li
- Department of Anesthesiology, The Affiliated Hospital, School of Medicine, UESTC Chengdu Women's & Children's Central Hospital, Chengdu, 610091, China
| | - Lingmei Deng
- Department of Anesthesiology, The Affiliated Hospital, School of Medicine, UESTC Chengdu Women's & Children's Central Hospital, Chengdu, 610091, China
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14
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Risk Factors for Sepsis-Associated Acute Kidney Injury in the PICU: A Retrospective Cohort Study. Pediatr Crit Care Med 2022; 23:e366-e370. [PMID: 35435886 DOI: 10.1097/pcc.0000000000002957] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Acute kidney injury (AKI), particularly of greater severity and longer duration, is associated with increased morbidity and mortality in the pediatric population. AKI frequently occurs during sepsis, yet the knowledge of risk factors for sepsis-associated AKI in the PICU is limited. We aimed to identify risk factors for AKI that develops or persists after 72 hours from sepsis recognition in pediatric patients with severe sepsis. DESIGN Retrospective cohort study. SETTING PICU at an academic, tertiary-care center. PATIENTS Children greater than 1 month and less than or equal to 18 years with severe sepsis in the combined cardiac and medical/surgical PICU between December 1, 2013, and December 31, 2020, at the University of Virginia Children's Hospital. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The cohort included 124 patients with severe sepsis with 33 patients (27%) who were postcardiac surgery with cardiopulmonary bypass. AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The primary outcome was severe AKI, defined as KDIGO stage 2 or 3 AKI present at any point between days 3 and 7 after sepsis recognition. Severe AKI was present in 25 patients (20%). Factors independently associated with severe AKI were maximum vasoactive-inotropic score (VIS) within 48 hours after sepsis recognition and fluid overload. The presence of severe AKI was associated with increased inhospital mortality. CONCLUSIONS In children with severe sepsis, the degree of hemodynamic support as measured by the VIS and the presence of fluid overload may identify patients at increased risk of developing severe AKI.
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15
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Murphy L, Maloney K, Gore L, Blanchette E. Hypertension in Pediatric Acute Lymphoblastic Leukemia Patients: Prevalence, Impact, and Management Strategies. Integr Blood Press Control 2022; 15:1-10. [PMID: 35082528 PMCID: PMC8784271 DOI: 10.2147/ibpc.s242244] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 11/17/2021] [Indexed: 01/27/2023] Open
Abstract
Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children under the age of 18. While modern diagnostic technologies, risk-stratification, and therapy intensification have led to outstanding outcomes for many children with ALL, the side effects and consequences of therapy are not to be underestimated. Hypertension is a well-known acute and chronic side effect of treatment for childhood ALL, although limited data are available regarding the prevalence of hypertension in children undergoing treatment for ALL. In this review of hypertension in pediatric ALL patients, we examine the existing data on incidence and prevalence during treatment and in pediatric ALL survivors. We describe independent risk factors for development of hypertension along with treatment-related causes. Long-term consequences and the risk to survivors of pediatric ALL are further defined. While many ALL patients require antihypertensive medications during some portion of their treatment, there are no clear guidelines on treating inpatient hypertension given challenges that exist in recognizing and managing hypertension in this setting and in this population. Here, we propose an algorithmic approach to diagnose and treat pediatric ALL patients with HTN, along with monitoring and continuation versus cessation of antihypertensive therapy as an outpatient.
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Affiliation(s)
- Lindsey Murphy
- Department of Pediatrics, Sections of Hematology/Oncology/Bone Marrow Transplant-Cellular Therapeutics, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO, USA
| | - Kelly Maloney
- Department of Pediatrics, Sections of Hematology/Oncology/Bone Marrow Transplant-Cellular Therapeutics, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO, USA
- University of Colorado Cancer Center, Aurora, CO, USA
| | - Lia Gore
- Department of Pediatrics, Sections of Hematology/Oncology/Bone Marrow Transplant-Cellular Therapeutics, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO, USA
- University of Colorado Cancer Center, Aurora, CO, USA
- Correspondence: Lia Gore Tel +17207776458Fax +17207777339 Email
| | - Eliza Blanchette
- Department of Pediatrics, Section of Nephrology, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO, USA
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16
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Gorga SM, Carlton EF, Kohne JG, Barbaro RP, Basu RK. Consensus acute kidney injury criteria integration identifies children at risk for long-term kidney dysfunction after multiple organ dysfunction syndrome. Pediatr Nephrol 2021; 36:1637-1646. [PMID: 33427986 PMCID: PMC8087651 DOI: 10.1007/s00467-020-04865-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 10/12/2020] [Accepted: 11/17/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND The consensus definition of acute kidney injury (AKI) has evolved since developing the original multiple organ dysfunction syndrome (MODS) definitions. Whether or not risk for adverse short- and long-term outcomes can be identified using the refined AKI criteria in the setting of MODS has not been studied. We hypothesize that incorporation of Kidney Disease: Improving Global Outcome (KDIGO) AKI criteria into existing MODS definitions will have a higher association with major adverse kidney events at 30 days (MAKE30) and will increase the number of patients with MODS. METHODS Post hoc analysis of 410 children admitted to a tertiary care pediatric intensive care unit (PICU) was conducted. MODS was defined using two existing criteria (Goldstein and Proulx) during the first 7 days following ICU admission and then modified by replacement of the kidney injury criteria using the KDIGO AKI definitions (G' and P'). RESULTS MAKE30 occurred in 65 of 410 (16%) children. After substituting KDIGO kidney injury criteria, identification of MAKE30 increased from 46 children (71%) to 53 (82%) and 29 children (45%) to 43 (66%) for the Goldstein and Proulx criteria, respectively. Additionally, identification of MODS increased from 194 (47%) by Goldstein to 224 (55%) by G' and 95 children (23%) by Proulx to 132 (32%) by P'. CONCLUSIONS Substituting KDIGO AKI criteria into existing MODS criteria increases the sensitivity for major adverse kidney events as well as the identification of MODS, improving the detection of children at risk for long-term adverse renal outcomes.
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Affiliation(s)
- Stephen M Gorga
- Department of Pediatrics, University of Michigan Medical School, 1500 E. Medical Center Drive, F-6890, Ann Arbor, MI, 48109, USA.
| | - Erin F Carlton
- Department of Pediatrics, University of Michigan Medical School, 1500 E. Medical Center Drive, F-6890, Ann Arbor, MI, 48109, USA
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor, MI, USA
| | - Joseph G Kohne
- Department of Pediatrics, University of Michigan Medical School, 1500 E. Medical Center Drive, F-6890, Ann Arbor, MI, 48109, USA
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor, MI, USA
| | - Ryan P Barbaro
- Department of Pediatrics, University of Michigan Medical School, 1500 E. Medical Center Drive, F-6890, Ann Arbor, MI, 48109, USA
- Susan B. Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor, MI, USA
| | - Rajit K Basu
- Children's Healthcare of Atlanta/Emory University, Atlanta, GA, USA
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17
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The application of omic technologies to research in sepsis-associated acute kidney injury. Pediatr Nephrol 2021; 36:1075-1086. [PMID: 32356189 PMCID: PMC7606209 DOI: 10.1007/s00467-020-04557-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 03/26/2020] [Accepted: 03/27/2020] [Indexed: 12/25/2022]
Abstract
Acute kidney injury (AKI) is common in critically ill children and adults, and sepsis-associated AKI (SA-AKI) is the most frequent cause of AKI in the ICU. To date, no mechanistically targeted therapeutic interventions have been identified. High-throughput "omic" technologies (e.g., genomics, proteomics, metabolomics, etc.) offer a new angle of approach to achieve this end. In this review, we provide an update on the current understanding of SA-AKI pathophysiology. Omic technologies themselves are briefly discussed to facilitate interpretation of studies using them. We next summarize the body of SA-AKI research to date that has employed omic technologies. Importantly, omic studies are helping to elucidate a pathophysiology of SA-AKI centered around cellular stress responses, metabolic changes, and dysregulation of energy production that underlie its clinical features. Finally, we propose opportunities for future research using clinically relevant animal models, integrating multiple omic technologies and ultimately progressing to translational human studies focusing therapeutic strategies on targeted disease mechanisms.
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18
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Selewski DT, Askenazi DJ, Kashani K, Basu RK, Gist KM, Harer MW, Jetton JG, Sutherland SM, Zappitelli M, Ronco C, Goldstein SL, Mottes TA. Quality improvement goals for pediatric acute kidney injury: pediatric applications of the 22nd Acute Disease Quality Initiative (ADQI) conference. Pediatr Nephrol 2021; 36:733-746. [PMID: 33433708 DOI: 10.1007/s00467-020-04828-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 09/24/2020] [Accepted: 10/15/2020] [Indexed: 02/07/2023]
Affiliation(s)
- David T Selewski
- Department of Pediatric, Medical University of South Carolina, 96 Jonathan Lucas St, CSB 428 MSC 608, Charleston, SC, 29425, USA.
| | - David J Askenazi
- Department of Pediatrics, University of Alabama Birmingham, Birmingham, AL, USA
| | - Kianoush Kashani
- Division of Nephrology and Hypertension, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Rajit K Basu
- Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA
| | - Katja M Gist
- Department of Pediatrics, Children's Hospital of Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Matthew W Harer
- Division of Neonatology, Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
| | - Jennifer G Jetton
- Division of Nephrology, Dialysis, and Transplantation, Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA, USA
| | - Scott M Sutherland
- Department of Pediatrics, Division of Nephrology, Stanford University, Stanford, CA, USA
| | - Michael Zappitelli
- Department of Pediatrics, Toronto Hospital for Sick Children, Toronto, Canada
| | - Claudio Ronco
- Department of Medicine, Department. Nephrology Dialysis & Transplantation, International Renal Research Institute, San Bortolo Hospital, University of Padova, Vicenza, Italy
| | - Stuart L Goldstein
- Center for Acute Care Nephrology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
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19
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Fitzgerald JC, Ross ME, Thomas NJ, Weiss SL, Balamuth F, Chilutti M, Grundmeier RW, Anderson AH. Association of early hypotension in pediatric sepsis with development of new or persistent acute kidney injury. Pediatr Nephrol 2021; 36:451-461. [PMID: 32710239 PMCID: PMC7856266 DOI: 10.1007/s00467-020-04704-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 06/17/2020] [Accepted: 06/30/2020] [Indexed: 01/20/2023]
Abstract
OBJECTIVE To determine how hypotension in the first 48 h of sepsis management impacts acute kidney injury (AKI) development and persistence. STUDY DESIGN Retrospective study of patients > 1 month to < 20 years old with sepsis in a pediatric ICU between November 2012 and January 2015 (n = 217). All systolic blood pressure (SBP) data documented within 48 h after sepsis recognition were collected and converted to percentiles for age, sex, and height. Time below SBP percentiles and below pediatric advanced life support (PALS) targets was calculated by summing elapsed time under SBP thresholds during the first 48 h. The primary outcome was new or persistent AKI, defined as stage 2 or 3 AKI present between sepsis day 3-7 using Kidney Disease: Improving Global Outcomes creatinine definitions. Secondary outcomes included AKI-free days (days alive and free of AKI) and time to kidney recovery. RESULTS Fifty of 217 sepsis patients (23%) had new or persistent AKI. Patients with AKI spent a median of 35 min under the first SBP percentile, versus 4 min in those without AKI. After adjustment for potential confounders, the odds of AKI increased by 9% with each doubling of minutes spent under this threshold (p = 0.03). Time under the first SBP percentile was also associated with fewer AKI-free days (p = 0.02). Time spent under PALS targets was not associated with AKI. CONCLUSIONS The duration of severe systolic hypotension in the first 48 h of pediatric sepsis management is associated with AKI incidence and duration when defined by age, sex, and height norms, but not by PALS definitions. Graphical abstract.
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Affiliation(s)
- Julie C Fitzgerald
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
- Department of Anesthesiology, Perelman School of Medicine, University of Pennsylvania, 3401 Civic Center Blvd., 6th Floor Wood Building, Room 6117, Philadelphia, PA, 19104, USA.
| | - Michelle E Ross
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Neal J Thomas
- Department of Pediatrics, Penn State Hershey Children's Hospital, Penn State University College of Medicine, Hershey, PA, USA
| | - Scott L Weiss
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Department of Anesthesiology, Perelman School of Medicine, University of Pennsylvania, 3401 Civic Center Blvd., 6th Floor Wood Building, Room 6117, Philadelphia, PA, 19104, USA
| | - Fran Balamuth
- Department of Pediatrics, Division of Emergency Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Marianne Chilutti
- Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Robert W Grundmeier
- Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Amanda Hyre Anderson
- Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA
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20
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Leghrouz B, Kaddourah A. Impact of Acute Kidney Injury on Critically Ill Children and Neonates. Front Pediatr 2021; 9:635631. [PMID: 33981652 PMCID: PMC8107239 DOI: 10.3389/fped.2021.635631] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 03/16/2021] [Indexed: 11/13/2022] Open
Abstract
Acute kidney injury (AKI) is a clinical syndrome that manifests as an abrupt impairment of kidney function. AKI is common in critically ill pediatric patients admitted to the pediatric intensive care units. AKI is a deleterious complication in critically ill children as it is associated with increased morbidity and mortality. This review provides an overview of the incidence, morbidity, and mortality of AKI in critically ill children in general and specific cohorts such as post-cardiac surgeries, sepsis, critically ill neonates, and post stem cell transplantation.
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Affiliation(s)
- Bassil Leghrouz
- Pediatric Nephrology and Hypertension Division, Sidra Medicine, Doha, Qatar
| | - Ahmad Kaddourah
- Pediatric Nephrology and Hypertension Division, Sidra Medicine, Doha, Qatar.,Weill Cornel Medical College, Ar-Rayyan, Qatar
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21
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Odum JD, Wong HR, Stanski NL. A Precision Medicine Approach to Biomarker Utilization in Pediatric Sepsis-Associated Acute Kidney Injury. Front Pediatr 2021; 9:632248. [PMID: 33937146 PMCID: PMC8079650 DOI: 10.3389/fped.2021.632248] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 03/22/2021] [Indexed: 12/29/2022] Open
Abstract
Sepsis is a leading cause of morbidity and mortality in critically ill children, and acute kidney injury (AKI) is a frequent complication that confers an increased risk for poor outcomes. Despite the documented consequences of sepsis-associated AKI (SA-AKI), no effective disease-modifying therapies have been identified to date. As such, the only treatment options for these patients remain prevention and supportive care, both of which rely on the ability to promptly and accurately identify at risk and affected individuals. To achieve these goals, a variety of biomarkers have been investigated to help augment our currently limited predictive and diagnostic strategies for SA-AKI, however, these have had variable success in pediatric sepsis. In this mini-review, we will briefly outline the current use of biomarkers for SA-AKI, and propose a new framework for biomarker discovery and utilization that considers the individual patient's sepsis inflammatory response. Now recognized to be a key driver in the complex pathophysiology of SA-AKI, understanding the dysregulated host immune response to sepsis is a growing area of research that can and should be leveraged to improve the prediction and diagnosis of SA-AKI, while also potentially identifying novel therapeutic targets. Reframing SA-AKI in this manner - as a direct consequence of the individual patient's sepsis inflammatory response - will facilitate a precision medicine approach to its management, something that is required to move the care of this consequential disorder forward.
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Affiliation(s)
- James D Odum
- Division of Critical Care, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - Hector R Wong
- Division of Critical Care, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Natalja L Stanski
- Division of Critical Care, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States
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22
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Cruz AT, Lane RD, Balamuth F, Aronson PL, Ashby DW, Neuman MI, Souganidis ES, Alpern ER, Schlapbach LJ. Updates on pediatric sepsis. J Am Coll Emerg Physicians Open 2020; 1:981-993. [PMID: 33145549 PMCID: PMC7593454 DOI: 10.1002/emp2.12173] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 06/02/2020] [Accepted: 06/05/2020] [Indexed: 12/11/2022] Open
Abstract
Sepsis, defined as an infection with dysregulated host response leading to life-threatening organ dysfunction, continues to carry a high potential for morbidity and mortality in children. The recognition of sepsis in children in the emergency department (ED) can be challenging, related to the high prevalence of common febrile infections, poor specificity of discriminating features, and the capacity of children to compensate until advanced stages of shock. Sepsis outcomes are strongly dependent on the timeliness of recognition and treatment, which has led to the successful implementation of quality improvement programs, increasing the reliability of sepsis treatment in many US institutions. We review clinical, laboratory, and technical modalities that can be incorporated into ED practice to facilitate the recognition, treatment, and reassessment of children with suspected sepsis. The 2020 updated pediatric sepsis guidelines are reviewed and framed in the context of ED interventions, including guidelines for antibiotic administration, fluid resuscitation, and the use of vasoactive agents. Despite a large body of literature on pediatric sepsis epidemiology in recent years, the evidence base for treatment and management components remains limited, implying an urgent need for large trials in this field. In conclusion, although the burden and impact of pediatric sepsis remains substantial, progress in our understanding of the disease and its management have led to revised guidelines and the available data emphasizes the importance of local quality improvement programs.
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Affiliation(s)
- Andrea T. Cruz
- Sections of Emergency Medicine and Infectious DiseaseDepartment of PediatricsBaylor College of MedicineHoustonTexasUSA
| | - Roni D. Lane
- Division of Pediatric Emergency Medicinethe University of Utah Primary Children's HospitalSalt Lake CityUtahUSA
| | - Fran Balamuth
- Division of Emergency MedicineDepartment of PediatricsUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPennsylvaniaUSA
| | - Paul L. Aronson
- Section of Pediatric Emergency MedicineDepartments of Pediatrics and Emergency MedicineYale School of MedicineNew HavenConnecticutUSA
| | - David W. Ashby
- Sections of Emergency Medicine and Infectious DiseaseDepartment of PediatricsBaylor College of MedicineHoustonTexasUSA
| | - Mark I. Neuman
- Division of Emergency MedicineDepartment of PediatricsBoston Children's HospitalBostonMassachusettsUSA
| | - Ellie S. Souganidis
- Sections of Emergency Medicine and Infectious DiseaseDepartment of PediatricsBaylor College of MedicineHoustonTexasUSA
| | - Elizabeth R. Alpern
- Division of Emergency MedicineDepartment of PediatricsAnn & Robert H. Lurie Children's HospitalFeinberg School of MedicineNorthwestern UniversityChicagoIllinoisUSA
| | - Luregn J. Schlapbach
- Department of Intensive Care Medicine and Neonatologyand Children's Research CenterUniversity Children's Hospital of ZurichUniversity of ZurichZurichSwitzerland
- Paediatric Critical Care Research GroupThe University of Queensland and Queensland Children's HospitalBrisbaneQueenslandAustralia
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Wu Y, Hua X, Yang G, Xiang B, Jiang X. Incidence, risk factors, and outcomes of acute kidney injury in neonates after surgical procedures. Pediatr Nephrol 2020; 35:1341-1346. [PMID: 32232634 DOI: 10.1007/s00467-020-04532-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Revised: 02/27/2020] [Accepted: 03/05/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Acute kidney injury (AKI) is common and associated with poor outcomes in critically ill neonates. The objective of this study was to study the incidence, risk factors, and clinical outcomes of AKI in neonates receiving non-cardiac surgery. METHODS We performed a single-center retrospective study between January 2017 and December 2018 of neonates who had received abdominal and thoracic surgical procedures. AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patient information, clinical data, and outcomes were collected and analyzed. Logistic regression was used to analyze risk factors of AKI and association between AKI and mortality. RESULTS Fifty-four (33.8%) of 160 patients developed AKI after surgical procedures. Compared with neonates without AKI, neonates with AKI had higher mortality rate (18.5% VS 5.7%, p = 0.022), lower gestational age (30.5 weeks, interquartile range [IQR] 28-33.5, VS 34.5 weeks, IQR 33-37.5, p = 0.035), higher rates of very low birth weight (33.3% VS 17.0%, p = 0.019), longer duration of mechanical ventilation (0.5 days, IQR 0-1.5, VS 0 days, IQR 0-1, p = 0.043) and higher rates of sepsis (35.2% VS 19.8%, p = 0.034). Risk factors of AKI included gestational age under 32 weeks (OR 4.8, 95% CI 1.8-12.6; p = 0.001), sepsis (OR 4.3, 95% CI 1.7-11.3; p = 0.003), operation time longer than 120 min (OR 2.7, 95% CI 1.1-6.6; p = 0.024), and diagnosis of necrotizing enterocolitis (OR 3.5, 95% CI 1.3-9.1; p = 0.011). AKI after surgery was significantly associated with mortality (OR 4.3, 95% CI 1.1-16.9; p = 0.036). CONCLUSIONS AKI is common and associated with poor outcomes in surgical neonates. Early recognition and intervention of AKI in these patients are important.
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Affiliation(s)
- Yang Wu
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xintian Hua
- Department of Neonatology, West China Second Hospital, Sichuan University, Chengdu, China
| | - Gang Yang
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Xiang
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoping Jiang
- Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China.
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Piyaphanee N, Chaiyaumporn S, Phumeetham S, Lomjansook K, Sumboonnanonda A. Acute kidney injury without previous renal disease in critical care unit. Pediatr Int 2020; 62:810-815. [PMID: 32145130 DOI: 10.1111/ped.14218] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 02/28/2020] [Accepted: 03/03/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND Acute kidney injury (AKI) is common in hospitalized and critically ill children. Apart from primary kidney disease, etiologies of AKI are usually related to systemic disease and nephrotoxic insult. This study examines the incidence, characteristics, and mortality risks of AKI in critically ill children without primary renal disease or previously known chronic kidney disease. METHODS A retrospective cohort study was conducted of patients aged 1-18 years, diagnosed with AKI (excluding severe glomerulonephritis and previously known chronic kidney disease) in pediatric intensive care units between 2013 and 2016. Acute kidney injury was defined according to the Kidney Disease Improving Global Outcomes classifications. Cox proportional hazards regression analysis was employed to assess the relationship between the risk factors and mortality. RESULTS Of 1,377 pediatric intensive care unit patients, 253 (18.4%) developed AKI and only 169 (12.3%) who did not have previously known renal disease were included. Of these 169 AKI patients, the mean age was 8.1 ± 4.7 years; 88 (52.1%) patients were male; and 60 (35.5%) patients had AKI stage 3. The most common etiologies of AKI were sepsis (76.9%) and shock (64.5%). Fifty-three (31.4%) of those patients died during admission. The risk factors for death were the need for mechanical ventilation (adjusted hazard ratio, 17.82; 95% CI, 2.41-132.06) and AKI stage 3 (adjusted hazard ratio, 2.32; 95% CI, 1.07-5.00). CONCLUSIONS Acute kidney injury in critically ill children without previously known renal disease was approximately two-thirds of the overall incidence. The risk factors of in-hospital death were the use of mechanical ventilation, and AKI stage 3.
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Affiliation(s)
- Nuntawan Piyaphanee
- Divisions of Nephrology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sivaporn Chaiyaumporn
- Divisions of Nephrology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Suwannee Phumeetham
- Divisions of Intensive Care, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Kraisoon Lomjansook
- Divisions of Nephrology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Achra Sumboonnanonda
- Divisions of Nephrology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Successful Single-kidney Transplantation in Adult Recipients Using Pediatric Donors Aged 8 to 36 Months: Comparable Outcomes With Those Using Pediatric Donors Aged >3 Years. Transplantation 2020; 103:2388-2396. [PMID: 30801522 DOI: 10.1097/tp.0000000000002618] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Using pediatric donors for single-kidney transplantation (SKT) can increase the number of possible recipients. However, it is unclear when SKT involving small pediatric donors and adult recipients can safely be performed without compromising graft outcome. METHODS From 2013 to 2017, a total of 102 SKTs in adult recipients were performed in our center using pediatric donors aged <12 years. We compared the outcomes from donors aged 8 to 36 months (the small-kidney group [SKG], n = 46) and from donors aged 3 to 12 years (the big-kidney group [BKG], n = 56). The median follow-up time was 30 months in the SKG and 28 months in the BKG. RESULTS All patients achieved satisfactory renal function after transplantation, despite the fact that some patients (SKG, 19.6%; BKG, 28.6%) developed delayed graft function. One-year graft survival and death-censored graft survival in the SKG were 89.1% and 100%, respectively, comparable to the results in the BKG (92.9% and 98.2%). One year later, the graft and patient survival rates in both groups remained unchanged. Pulmonary infection was the main cause of death in patients with a functioning graft (SKG, 4 patients; BKG, 2 patients). Proteinuria occurred early in some patients (SKG, 30.4%; BKG, 19.6%) and decreased gradually within the first year posttransplantation. CONCLUSIONS SKT from pediatric donors aged 8 to 36 months to selected adult recipients produced excellent intermediate-term outcomes, comparable with those when older pediatric donors were used. This study provides evidence to support a lower age limit for SKT from pediatric donors.
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Searns JB, Gist KM, Brinton JT, Pickett K, Todd J, Birkholz M, Soranno DE. Impact of acute kidney injury and nephrotoxic exposure on hospital length of stay. Pediatr Nephrol 2020; 35:799-806. [PMID: 31940070 DOI: 10.1007/s00467-019-04431-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 10/14/2019] [Accepted: 11/19/2019] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Acute kidney injury (AKI) is a common occurrence among hospitalized children and leads to increased mortality and prolonged length of stay (LOS) in critically ill patients. Few studies have examined the impact of AKI on LOS for common pediatric conditions. We hypothesized that a diagnosis of AKI would be associated with a longer hospital LOS and increased exposure to nephrotoxic medications for all patients. PATIENTS AND METHODS We performed a multicenter retrospective cross-sectional analysis of 34 children's hospitals in the Pediatric Health Information System (PHIS) database from 1/2009 through 12/2013. Patients were grouped based on primary discharge diagnosis, number of days spent in an intensive care unit, and assignment of a secondary diagnostic code for AKI. Median LOS was compared among different patient groupings. Exposure to commonly used nephrotoxic medications was collected for each admission. RESULTS A total of 588,884 admissions from 423,337 patients were included in the analysis. The median LOS among non-critically ill patients with and without AKI was 5 days [95% CI 3-10] versus 2 days [95% CI 1-4], respectively. Among critically ill patients, median LOS for those with and without AKI was 12 days [95% CI 7-20] versus 4 days [95% CI 2-7], respectively. Patients who developed AKI were more likely to have significant nephrotoxic exposure. CONCLUSIONS Development of AKI was associated with longer hospital length of stay and increased nephrotoxic medication exposure for all diagnostic categories. Non-critically ill children with AKI were hospitalized the same length or longer than critically ill children without AKI.
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Affiliation(s)
- Justin B Searns
- Divisions of Hospital Medicine & Infectious Diseases, Children's Hospital Colorado, Department of Pediatrics, University of Colorado, Aurora, CO, USA
| | - Katja M Gist
- Division of Cardiology, Children's Hospital Colorado, Department of Pediatrics, University of Colorado, Aurora, CO, USA
| | - John T Brinton
- Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado, Aurora, CO, USA
| | - Kaci Pickett
- Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado, Aurora, CO, USA
| | - James Todd
- Division of Infectious Diseases, Children's Hospital Colorado, Department of Pediatrics, University of Colorado, Aurora, CO, USA
| | - Meghan Birkholz
- Division of Infectious Diseases, Children's Hospital Colorado, Department of Pediatrics, University of Colorado, Aurora, CO, USA
| | - Danielle E Soranno
- Division of Nephrology, Children's Hospital Colorado, Department of Pediatrics, Bioengineering and Medicine, University of Colorado, Aurora, CO, USA.
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Stanski NL, Stenson EK, Cvijanovich NZ, Weiss SL, Fitzgerald JC, Bigham MT, Jain PN, Schwarz A, Lutfi R, Nowak J, Allen GL, Thomas NJ, Grunwell JR, Baines T, Quasney M, Haileselassie B, Wong HR. PERSEVERE Biomarkers Predict Severe Acute Kidney Injury and Renal Recovery in Pediatric Septic Shock. Am J Respir Crit Care Med 2020; 201:848-855. [PMID: 31916857 PMCID: PMC7124707 DOI: 10.1164/rccm.201911-2187oc] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 01/07/2020] [Indexed: 12/23/2022] Open
Abstract
Rationale: Acute kidney injury (AKI), a common complication of sepsis, is associated with substantial morbidity and mortality and lacks definitive disease-modifying therapy. Early, reliable identification of at-risk patients is important for targeted implementation of renal protective measures. The updated Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) is a validated, multibiomarker prognostic enrichment strategy to estimate baseline mortality risk in pediatric septic shock.Objectives: To assess the association between PERSEVERE-II mortality probability and the development of severe, sepsis-associated AKI on Day 3 (D3 SA-AKI) in pediatric septic shock.Methods: We performed secondary analysis of a prospective observational study of children with septic shock in whom the PERSEVERE biomarkers were measured to assign a PERSEVERE-II baseline mortality risk.Measurements and Main Results: Among 379 patients, 65 (17%) developed severe D3 SA-AKI. The proportion of patients developing severe D3 SA-AKI increased directly with increasing PERSEVERE-II risk category, and increasing PERSEVERE-II mortality probability was independently associated with increased odds of severe D3 SA-AKI after adjustment for age and illness severity (odds ratio, 1.4; 95% confidence interval, 1.2-1.7; P < 0.001). Similar associations were found between increasing PERSEVERE-II mortality probability and the need for renal replacement therapy. Lower PERSEVERE-II mortality probability was independently associated with increased odds of renal recovery among patients with early AKI. A newly derived model incorporating the PERSEVERE biomarkers and Day 1 AKI status predicted severe D3 SA-AKI with an area under the received operating characteristic curve of 0.95 (95% confidence interval, 0.92-0.98).Conclusions: Among children with septic shock, the PERSEVERE biomarkers predict severe D3 SA-AKI and identify patients with early AKI who are likely to recover.
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Affiliation(s)
| | | | - Natalie Z. Cvijanovich
- University of California San Francisco Benioff Children’s Hospital Oakland, Oakland, California
| | - Scott L. Weiss
- Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | | | | | - Parag N. Jain
- Texas Children’s Hospital and Baylor College of Medicine, Houston, Texas
| | - Adam Schwarz
- Children’s Hospital of Orange County, Orange, California
| | - Riad Lutfi
- Riley Hospital for Children, Indianapolis, Indiana
| | - Jeffrey Nowak
- Children’s Hospital and Clinics of Minnesota, Minneapolis, Minnesota
| | | | - Neal J. Thomas
- Penn State Hershey Children’s Hospital, Hershey, Pennsylvania
| | | | | | - Michael Quasney
- C.S. Mott Children’s Hospital at the University of Michigan, Ann Arbor, Michigan
| | | | - Hector R. Wong
- Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Weiss SL, Balamuth F, Thurm CW, Downes KJ, Fitzgerald JC, Laskin BL. Major Adverse Kidney Events in Pediatric Sepsis. Clin J Am Soc Nephrol 2019; 14:664-672. [PMID: 31000518 PMCID: PMC6500940 DOI: 10.2215/cjn.12201018] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 02/20/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND OBJECTIVES Major adverse kidney events, a composite of death, new kidney replacement therapy, or persistent kidney dysfunction, is a potential patient-centered outcome for clinical trials in sepsis-associated kidney injury. We sought to determine the incidence of major adverse kidney events within 30 days and validate this end point in pediatric sepsis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a retrospective observational study using the Pediatric Health Information Systems Plus database of patients >6 months to <18 years old with a diagnosis of severe sepsis/septic shock; orders for bacterial blood culture, antibiotics, and at least one fluid bolus on hospital day 0/1; and known hospital disposition between January 2007 and December 2011. The primary outcome was incidence of major adverse kidney events within 30 days. Major adverse kidney events within 30 days were validated against all-cause mortality at hospital discharge, hospital length of stay, total hospital costs, hospital readmission within 30 days and 1 year, and lowest eGFR between 3 months and 1 year after discharge. We reported incidence of major adverse kidney events within 30 days with 95% confidence intervals using robust SEM and used multivariable logistic regression to test the association of major adverse kidney events within 30 days with hospital costs and mortality. RESULTS Of 1685 admissions, incidence of major adverse kidney events within 30 days was 9.6% (95% confidence interval, 8.1% to 11.0%), including 4.5% (95% confidence interval, 3.5% to 5.4%) death, 1.7% (95% confidence interval, 1.1% to 2.3%) kidney replacement therapy, and 5.8% (95% confidence interval, 4.7% to 6.9%) persistent kidney dysfunction. Patients with versus without major adverse kidney events within 30 days had higher all-cause mortality at hospital discharge (28% versus 1%; P<0.001), higher total hospital costs ($61,188; interquartile range, $21,272-140,356 versus $28,107; interquartile range, $13,056-72,697; P<0.001), and higher proportion with eGFR<60 ml/min per 1.73 m2 between 3 months and 1 year after discharge (19% versus 4%; P=0.001). Major adverse kidney events within 30 days was not associated with length of stay or readmissions. CONCLUSIONS In children with sepsis, major adverse kidney events within 30 days are common, feasible to measure, and a promising end point for future clinical trials.
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Affiliation(s)
- Scott L Weiss
- Departments of Anesthesiology and Critical Care and .,Pediatric Sepsis Program at the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.,Center for Mitochondrial and Epigenomic Medicine at the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Fran Balamuth
- Pediatric Sepsis Program at the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.,Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.,Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and
| | | | - Kevin J Downes
- Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.,Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and
| | - Julie C Fitzgerald
- Departments of Anesthesiology and Critical Care and.,Pediatric Sepsis Program at the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Benjamin L Laskin
- Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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