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Tan L, Zhou H, Lai Z, Yang G, Zheng F, Xiao F, Xiong Z, Huang X, Xiong Z. Brain peptides modified exosome-mediated drug delivery system for adriamycin-induced nephropathy treatment. NANOMEDICINE : NANOTECHNOLOGY, BIOLOGY, AND MEDICINE 2025; 66:102819. [PMID: 40174740 DOI: 10.1016/j.nano.2025.102819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 03/10/2025] [Accepted: 03/27/2025] [Indexed: 04/04/2025]
Abstract
Mitigation of adriamycin (ADR)-induced nephropathy remains a significant challenge in clinical management. Brain-targeted administration of losartan demonstrates comparable nephroprotective effects at a 1:500 concentration relative to gavage administration. This study established an exosome-based nano-delivery platform (ExoACP) to reduce drug dosage for alleviating ADR-induced nephropathy. The platform was rigorously tested for toxicity and blood-brain barrier penetration. Additionally, the role and possible mechanism of ExoACP-Los in alleviating ADR-induced nephropathy in mice were investigated. ExoACP showed enhanced penetration in brain microvascular endothelial cells, with a 7.20-fold increase in uptake. In the ADR model, ExoACP-Los exhibited anti-inflammatory and anti-fibrotic effects by downregulating the renin-angiotensin system, reducing extracellular matrix deposition by nearly half. These findings suggest ExoACP-Los can alleviate ADR-induced nephropathy by enhancing targeted drug delivery to the brain while reducing losartan. Overall, ExoACP holds significant potential for future clinical applications in chronic nephropathy.
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Affiliation(s)
- Lishan Tan
- Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen 518000, China
| | - Huisong Zhou
- Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen 518000, China; Department of Nephrology, Wenjiang District People's Hospital, Chengdu 610203, China
| | - Zhiwei Lai
- Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen 518000, China
| | - Guang Yang
- Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen 518000, China
| | - Fengping Zheng
- Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen 518000, China
| | - Fei Xiao
- Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen 518000, China
| | - Zuying Xiong
- Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen 518000, China
| | - Xiaoyan Huang
- Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen 518000, China; Clinical Research Academy, Peking University Shenzhen Hospital, Peking University, Shenzhen 518000, China.
| | - Zibo Xiong
- Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen 518000, China.
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Karmakar S, Dasgupta D, Akhtar S, Poddar S, Giri PP, Tse Y, Sinha R. Progression of acute kidney injury to chronic kidney disease: a prospective cohort study. Pediatr Nephrol 2025:10.1007/s00467-025-06810-5. [PMID: 40397129 DOI: 10.1007/s00467-025-06810-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 04/03/2025] [Accepted: 04/29/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND Prospective studies on kidney outcomes in critically ill children with acute kidney injury (AKI) are scarce from low- and middle-income countries (LMIC). We conducted a pilot study to evaluate the continuum of transient AKI-persistent AKI-acute kidney disease (AKD) and chronic kidney disease (CKD). METHODS Children (1-18 years) admitted to our tertiary Pediatric Intensive Care Unit (PICU) and developing AKI with no known pre-existing kidney co-morbidities from January 2021 to June 2022 were included with follow up visits at 1 and 3 months after AKI onset. AKI and CKD were defined as per KDIGO 2012. At risk of CKD was defined by albuminuria, hypertension, estimated glomerular filtration rate (eGFR) 60-90 ml/kg/1.73 m2 or hyperfiltration (eGFR ≥ 150 ml/kg/1.73 m2). RESULTS Of 390 children, 15% (n = 57) developed AKI. 75% (n = 43) with AKI had underlying primarily non-kidney systemic etiology. Fourteen (25%) died at median 5 days (IQR 4-7) after admission, and three were lost to follow up after discharge. For the 40 AKI survivors with three months data, incidence of transient AKI was 40% (n = 16), persistent AKI 20% (n = 8), AKD 32% (n = 13), and CKD 8% (n = 3). In addition, 18% (n = 7) were at risk of CKD. 38% with AKI for > 48 h vs. 6% with AKI < 48 h developed CKD or were at risk of CKD (p = 0.025). All three AKI survivors who progressed to CKD had an underlying primarily kidney etiology and progressed from AKD to CKD. CONCLUSIONS In this LMIC study, kidney sequelae were high at 3 months among PICU AKI survivors. This pilot supports the need and feasibility of larger prospective trials in LMIC settings to understand outcomes for all children with AKI.
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Affiliation(s)
- Shreyashi Karmakar
- Division of Pediatric Nephrology, Institute of Child Health, Kolkata, India
| | - Deblina Dasgupta
- Division of Pediatric Nephrology, Institute of Child Health, Kolkata, India
| | - Shakil Akhtar
- Division of Pediatric Nephrology, Institute of Child Health, Kolkata, India
| | - Sanjukta Poddar
- Division of Pediatric Nephrology, Institute of Child Health, Kolkata, India
| | - Prabhas Prasun Giri
- Division of Pediatric Intensive Care, Institute of Child Health, Kolkata, India
| | - Yincent Tse
- Division of Pediatric Nephrology, Great North Children Hospital, Newcastle, UK
| | - Rajiv Sinha
- Division of Pediatric Intensive Care, Institute of Child Health, Kolkata, India.
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Kubura DT, Mekonnen GB, Nigisi HD, Shibiru T, Legesse BT. Incidence and predictors of mortality among children admitted to intensive care unit in tertiary hospitals of West Oromia, Ethiopia. J Pediatr Nurs 2025; 83:160-167. [PMID: 40334569 DOI: 10.1016/j.pedn.2025.05.001] [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: 09/19/2024] [Revised: 04/30/2025] [Accepted: 05/01/2025] [Indexed: 05/09/2025]
Abstract
BACKGROUND Child mortality related to intensive care unit admission is a contributor to child death, which is preventable to some extent if identified early. This study aimed to determine the incidence and predictors of mortality among children admitted to intensive care units in tertiary hospitals in West Ethiopia. METHODS A retrospective follow-up study involving 578 admitted children from June 1, 2018, to May 30, 2023, was conducted in western Ethiopia. Data was entered into Epi-Data and then exported to STATA version 14 for analysis. The Cox proportional hazard assumption was checked. The best-fitted model for the data analysis was chosen based on the Akaike information criteria. The hazard ratio was used to measure the strength of the association at p-value <0.05 with 95 % CI. RESULT 578 charts were reviewed, and two hundred (34.6 %) children died. The incidence of mortality was 42.5 deaths per 1000-day observations. The median survival time was 15 days (95 % CI: 13 to 18). The need for Inotropes (AHR 2.1; 95 % CI: 1.34-3.09], complications in ICU (AHR 3.5, 95 % CI: 2.2-5.78], GCS < 8 (AHR 1.72, 95 % CI: 1.22-2.46], acute kidney injury (AHR 2.0, 95 % CI: 1.12-3.59] and Age < 5 years (AHR 1.91, 95 % CI: 1.26-2.896] were independent predictors of mortality. CONCLUSION The incidence of mortality was 42.5 deaths per 1000 pediatric day observations. Acute kidney injury, the need for inotropes, age < 5 years, low Glasgow coma scale, and complications developed in the intensive care unit were independent predictors of death.
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Affiliation(s)
- Dessalegn Tekalign Kubura
- Department of Pediatrics and Child Health Nursing, Nekemte Comprehensive Specialized Hospital, Ethiopia
| | - Gebrehiwot Berie Mekonnen
- Department of Pediatrics and Child Health Nursing, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | | | - Tesfaye Shibiru
- School of Medicine, Institute of Health Sciences, Wollega University, Nekemte, Ethiopia
| | - Bruck Tesfaye Legesse
- Department of Pediatrics and Neonatal Nursing, School of Nursing and Midwifery, Institute of Health Sciences, Wollega University, Nekemte, Ethiopia.
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Dixon CG, Trujillo Rivera EA, Patel AK, Pollack MM. Development of a neural network model for early detection of creatinine change in critically Ill children. Front Pediatr 2025; 13:1549836. [PMID: 40256396 PMCID: PMC12006092 DOI: 10.3389/fped.2025.1549836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Accepted: 03/14/2025] [Indexed: 04/22/2025] Open
Abstract
Introduction Renal dysfunction is common in critically ill children and increases morbidity and mortality risk. Diagnosis and management of renal dysfunction relies on creatinine, a delayed marker of renal injury. We aimed to develop and validate a machine learning model using routinely collected clinical data to predict 24-hour creatinine change in critically ill children before change is observed clinically. Methods Retrospective cohort study of 39,932 pediatric intensive care unit encounters in a national multicenter database from 2007 to 2022. A neural network was trained to predict <50% or ≥50% creatinine change in the next 24 h. Admission demographics, routinely measured vital signs, laboratory tests, and medication use variables were used as predictors for the model. Data set was randomly split at the encounter level into model development (80%) and test (20%) sets. Performance and clinical relevance was assessed in the test set by accuracy of prediction classification and confusion matrix metrics. Results The cohort had a male predominance (53.8%), median age of 8.0 years (IQR 1.9-14.6), 21.0% incidence of acute kidney injury, and 2.3% mortality. The overall accuracy of the model for predicting change of <50% or ≥50% was 68.1% (95% CI 67.6%-68.7%). The accuracy of classification improved substantially with higher creatinine values from 29.9% (CI 28.9%-31.0%) in pairs with an admission creatinine <0.3 mg/dl to 90.0-96.3% in pairs with an admission creatinine of ≥0.6 mg/dl. The model had a negative predictive value of 97.2% and a positive predictive value of 7.1%. The number needed to evaluate to detect one true change ≥50% was 14. Discussion 24-hour creatinine change consistent with acute kidney injury can be predicted using routine clinical data in a machine learning model, indicating risk of significant renal dysfunction before it is measured clinically. Positive predictive performance is limited by clinical reliance on creatinine.
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Affiliation(s)
- Celeste G. Dixon
- Department of Pediatrics, Division of Critical Care Medicine, Children's National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC, United States
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Reddy RK, Menon S, Selewski DT. Putting the injury back into AKI: understanding AKI phenotypes and improving risk assessment in cardiac surgery-associated AKI. Pediatr Nephrol 2025; 40:887-890. [PMID: 39656275 DOI: 10.1007/s00467-024-06617-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 11/21/2024] [Accepted: 11/21/2024] [Indexed: 03/08/2025]
Affiliation(s)
- Reshma K Reddy
- Division of Cardiology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA
| | - Shina Menon
- Division of Nephrology, Department of Pediatrics, Stanford University School of Medicine, Lucile Packard Children's Hospital, Palo Alto, CA, USA
| | - David T Selewski
- Division of Nephrology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
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Ulrich EH, Yordanova M, Morgan C, Benisty K, Riglea T, Huynh L, Crépeau-Hubert F, Hessey E, McMahon K, Cockovski V, Wang S, Zappitelli M. Kidney and blood pressure outcomes 11 years after pediatric critical illness and longitudinal impact of AKI: a prospective cohort study. Pediatr Nephrol 2025; 40:1111-1120. [PMID: 39585355 DOI: 10.1007/s00467-024-06586-0] [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: 02/14/2024] [Revised: 10/10/2024] [Accepted: 10/23/2024] [Indexed: 11/26/2024]
Abstract
BACKGROUND Acute kidney injury (AKI) is common in critically ill children and associated with adverse short-term outcomes; however, long-term outcomes are not well described. METHODS This longitudinal prospective cohort study examined the prevalence of chronic kidney disease (CKD) and hypertension (HTN) 11 vs. 6 years after pediatric intensive care unit (PICU) admission and association with AKI. We examined children (age < 19 years) without pre-existing kidney disease 11 ± 1.5 years after PICU admission at a single center. AKI was defined using serum creatinine criteria. The primary outcome was a composite of CKD or HTN. CKD was defined as estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 or albuminuria. Multivariable analyses compared outcomes at 11- vs. 6-year follow-up and association with AKI during PICU admission. RESULTS Of 96 children evaluated 11 years after PICU admission, 16% had evidence of CKD or HTN (vs. 28% at 6 years, p < 0.05). Multivariable analysis did not show improvement in outcomes from 6- to 11-year follow-up. eGFR decreased from 6- to 11-year follow-up (adjusted coefficient - 11.7, 95% CI - 17.6 to - 5.9) and systolic and diastolic blood pressures improved. AKI was associated with composite outcome at 6-year (adjusted odds ratio (aOR) 12.7, 95% CI 3.2-51.2, p < 0.001), but not 11-year follow-up (p = 0.31). AKI was associated with CKD (aOR 10.4, 95% CI 3.1-34.7) at 11 years. CONCLUSIONS This study provides novel data showing that adverse kidney and blood pressure outcomes remain highly prevalent 10 years after critical illness in childhood. The association with AKI wanes over time.
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Affiliation(s)
- Emma H Ulrich
- Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
| | - Mariya Yordanova
- Faculty of Medicine and Dentistry, McGill University Health Centre, Montreal, QC, Canada
| | - Catherine Morgan
- Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
| | - Kelly Benisty
- Faculty of Medicine and Dentistry, McGill University Health Centre, Montreal, QC, Canada
| | - Teodora Riglea
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada
| | - Louis Huynh
- Faculty of Medicine and Dentistry, McGill University Health Centre, Montreal, QC, Canada
| | | | - Erin Hessey
- Department of Pediatrics, Toronto Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, University of Toronto, 686 Bay Street, Room 11.9722, Toronto, ON, M5G 0A4, Canada
| | - Kelly McMahon
- Faculty of Medicine and Dentistry, McGill University Health Centre, Montreal, QC, Canada
| | - Vedran Cockovski
- Department of Pediatrics, Toronto Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, University of Toronto, 686 Bay Street, Room 11.9722, Toronto, ON, M5G 0A4, Canada
| | - Stella Wang
- Department of Pediatrics, Toronto Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, University of Toronto, 686 Bay Street, Room 11.9722, Toronto, ON, M5G 0A4, Canada
| | - Michael Zappitelli
- Department of Pediatrics, Toronto Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, University of Toronto, 686 Bay Street, Room 11.9722, Toronto, ON, M5G 0A4, Canada.
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Krishnasamy S, Sinha A, Lodha R, Sankar J, Tarik M, Ramakrishnan L, Bagga A, Hari P. Furosemide stress test to predict acute kidney injury progression in critically ill children. Pediatr Nephrol 2025; 40:243-251. [PMID: 38691152 DOI: 10.1007/s00467-024-06387-5] [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: 01/31/2024] [Revised: 04/10/2024] [Accepted: 04/10/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND Furosemide stress test (FST) is a novel functional biomarker for predicting severe acute kidney injury (AKI); however, pediatric studies are limited. METHODS Children 3 months to 18 years of age admitted to the intensive care unit (ICU) of a tertiary care hospital from Nov 2019 to July 2021 were screened and those who developed AKI stage 1 or 2 within 7 days of admission underwent FST (intravenous furosemide 1 mg/kg). Urine output was measured hourly for the next 6 h; a value > 2 ml/kg within the first 2 h was deemed furosemide responsive. Other biomarkers like plasma neutrophil gelatinase-associated lipocalin (NGAL) and proenkephalin (PENK) were also evaluated. RESULTS Of the 480 admitted patients, 51 developed AKI stage 1 or 2 within 7 days of admission and underwent FST. Nine of these patients were furosemide non-responsive. Thirteen (25.5%) patients (eight of nine from FST non-responsive group) developed stage 3 AKI within 7 days of FST, nine (17.6%) of whom (seven from non-responsive group) required kidney support therapy (KST). FST emerged as a good biomarker for predicting stage 3 AKI and need for KST with area-under-the-curve (AUC) being 0.93 ± 0.05 (95% CI 0.84-1.0) and 0.96 ± 0.03 (95% CI 0.9-1.0), respectively. FST outperformed NGAL and PENK in predicting AKI stage 3 and KST; however, the combination did not improve the diagnostic accuracy. CONCLUSIONS Furosemide stress test is a simple, inexpensive, and robust biomarker for predicting stage 3 AKI and KST need in critically ill children. Further research is required to identify the best FST cut-off in children.
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Affiliation(s)
- Sudarsan Krishnasamy
- Pediatric Nephrology Services, Department of Paediatrics, Jawaharlal Institute of Post Graduate Medical Education and Research (JIPMER), Pondicherry, India
| | - Aditi Sinha
- Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Rakesh Lodha
- Division of Pediatric Pulmonology and Intensive Care, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Jhuma Sankar
- Division of Pediatric Pulmonology and Intensive Care, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Mohamad Tarik
- Department of Cardiac Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Lakshmy Ramakrishnan
- Department of Cardiac Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Arvind Bagga
- Director Paediatrics and Senior Consultant Pediatric Nephrology, Indraprastha Apollo Hospitals, New Delhi, India
| | - Pankaj Hari
- Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
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Alayed T, Alansary A, Al-Nahdi M, Alotaibi A, Alhuthil R, Al Abdulsalam M, Aljofan F, Alturki A, Alofisan T. Incidence, outcomes, and mortality risk factors of acute kidney injury in critically ill children: a tertiary care center study in Saudi Arabia. Ann Saudi Med 2025; 45:62-68. [PMID: 39929790 PMCID: PMC11810873 DOI: 10.5144/0256-4947.2025.62] [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: 10/28/2024] [Accepted: 12/22/2024] [Indexed: 02/13/2025] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a critical concern in pediatric intensive care units (PICUs) due to its high mortality rate. OBJECTIVES Investigate AKI incidence, outcomes, and mortality-related risk factors among critically ill children. DESIGN Retrospective cohort. SETTING A PICU. PATIENTS AND METHODS The study included children (aged 4 weeks to 14 years) who were admitted to the PICU from (2016 to 2019) and developed AKI at King Faisal Specialist Hopsital and Research Centre. MAIN OUTCOMES MEASURES AKI incidence, outcomes, and mortality-related risk factors. SAMPLE SIZE 111 records of patients with AKI. RESULTS Of 969 PICU admissions, 111 cases developed AKI and were entered in the analysis, with an incidence rate of (11.5%). The median age was 43 months [interquartile range (IQR): 16-120], with hematology/oncology conditions being the most prevalent underlying diseases (56.8%). Septic shock and nephrotoxin medications were the leading causes of AKI, accounting for (46.8%) and (45.0%), respectively. Regarding AKI severity, (37.8%) were classified as stage 1, (25.2%) as stage 2, and (37.0%) as stage 3 AKI. As for PICU interventions, the highest was inotropic support (63.1%), followed by mechanical ventilation (56.8%) and renal replacement therapy (23.4%). The PICU mortality rate was (38.7%) (43/111), with no significant association between AKI stage and mortality. However, the multivariable analysis identified bone marrow transplant (BMT) (P=.042) and inotropic support (P=.001) as significant predictors of mortality. CONCLUSION These findings underscore the importance of early recognition and tailored management of AKI in PICU settings. Despite advancements in critical care, AKI remains a significant challenge, contributing to prolonged hospitalization, mortality, and increased health-care resource utilization. Therefore, more investigation is warranted. LIMITATIONS Retrospective study single-center nature.
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Affiliation(s)
- Tareq Alayed
- From the Department of Critical Care Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Abdulaziz Alansary
- From the Department of Critical Care Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Mohammed Al-Nahdi
- From the Department of Pediatrics, Dr. Soliman Fakeeh Hospital, Jeddah, Saudi Arabia
| | - Abdullah Alotaibi
- From the Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Raghad Alhuthil
- From the Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Moath Al Abdulsalam
- From the Department of Critical Care Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Fahad Aljofan
- From the Department of Critical Care Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Abdullah Alturki
- From the Department of Critical Care Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Tariq Alofisan
- From the Department of Critical Care Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
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Morgan C, Forest E, Ulrich E, Sutherland S. Pediatric acute kidney injury and adverse health outcomes: using a foundational framework to evaluate a causal link. Pediatr Nephrol 2024; 39:3425-3438. [PMID: 38951220 PMCID: PMC11511696 DOI: 10.1007/s00467-024-06437-y] [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: 11/22/2023] [Revised: 05/06/2024] [Accepted: 06/12/2024] [Indexed: 07/03/2024]
Abstract
Acute kidney injury (AKI) is a major global health problem, expensive to manage, and its associations with negative pediatric health outcomes have been clearly demonstrated. One of the most fundamental questions to consider as we use previous epidemiological information to advance research and care paradigms is the strength of the causal link between pediatric AKI and health outcomes. In this review, we apply the foundational framework of the Bradford Hill criteria to evaluate the extent to which a causal link exists between AKI and the associated adverse outcomes in children. Available data in children support a causal link between AKI and short-term outcomes including mortality, length of stay, and ventilation time. Clarifying the causal nature of longer term associations requires further high-quality observational studies in children, careful consideration of what defines the most meaningful and measurable longer term outcomes after pediatric AKI, and integration of evolving biological data related to mechanisms of disease. Preventing or mitigating AKI should lead to improved outcomes. Demonstrating such reversibility will solidify confidence in the causal relationship, improve child health, and highlight an aspect which is highly relevant to clinicians, scientists, and policy makers.
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Affiliation(s)
- Catherine Morgan
- Department of Pediatrics, Division of Nephrology, University of Alberta, Edmonton, AB, Canada.
| | - Emma Forest
- School of Public Health, University of Alberta, Edmonton, AB, Canada
| | - Emma Ulrich
- Department of Pediatrics, Division of Nephrology, University of Alberta, Edmonton, AB, Canada
| | - Scott Sutherland
- Department of Pediatrics, Division of Nephrology, Center for Academic Medicine, Stanford University School of Medicine, Palo Alto, CA, USA
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Sethi SK, Raina R, Sawan A, Asim S, Khant AK, Matnani M, Ganesan K, Lohia S, Sinha R, Rumana J, Haque SS, Kalra S, Safdar R, Prasad G, Ijaz I, Ashruf OS, Nair A, S S, Soni K, Shrestha D, Yadav S, Abeyagunawardena A, Luyckx VA, Alhasan KA, Sultana A. RETRACTED ARTICLE: Assessment of South Asian Pediatric Acute Kidney Injury: Epidemiology and Risk Factors (ASPIRE)-a prospective study on "severe dialysis dependent pediatric AKI". Pediatr Nephrol 2024; 39:3453. [PMID: 38456915 DOI: 10.1007/s00467-024-06324-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 02/03/2024] [Accepted: 02/13/2024] [Indexed: 03/09/2024]
Affiliation(s)
- Sidharth Kumar Sethi
- Department of Pediatric Nephrology and Pediatric Kidney Transplantation, Kidney and Urology Institute, Medanta, The Medicity Hospital, Gurgaon, India.
| | - Rupesh Raina
- Department of Nephrology, Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA
- Department of Nephrology, Akron Children's Hospital, Akron, OH, USA
| | - Ahmad Sawan
- Department of Nephrology, Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA
| | - Sadaf Asim
- National Institute of Child Health, Karachi, Pakistan
| | | | - Manoj Matnani
- Department of Pediatrics, Dr. D.Y Patil Medical College and Hospital, Pune, Maharashtra, India
| | | | - Shraddha Lohia
- Bharati Vidyapeeth Deemed University, Pune, Maharashtra, India
| | - Rajiv Sinha
- Division of Paediatric Nephrology, Institute of Child Health, Kolkata, West Bengal, India
| | | | - Syed Saimul Haque
- Bangabandhu Sheikh Mujib Medical University Hospital, Dhaka, Bangladesh
| | - Suprita Kalra
- Army Hospital Research and Referral, New Delhi, India
| | - Rabia Safdar
- Department of Pediatric Nephrology, Nishtar Medical University, Multan, Pakistan
| | - Gopal Prasad
- Department of Nephrology, Patna Medical College and Hospital, Patna, India
| | - Iftikhar Ijaz
- Children Kidney Center, Department of Pediatrics, King Edward Medical University, Lahore, Pakistan
| | - Omer S Ashruf
- Department of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH, USA
| | - Aishwarya Nair
- Department of Pediatric Nephrology and Pediatric Kidney Transplantation, Kidney and Urology Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Savita S
- Department of Pediatric Nephrology and Pediatric Kidney Transplantation, Kidney and Urology Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Kritika Soni
- Department of Pediatric Nephrology and Pediatric Kidney Transplantation, Kidney and Urology Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | | | | | - Asiri Abeyagunawardena
- Department of Paediatrics, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Valerie A Luyckx
- Department of Public and Global Health, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
- Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Paediatric and Child Health, University of Cape Town, Cape Town, South Africa
| | - Khalid A Alhasan
- Pediatric Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Azmeri Sultana
- Dr. MR Khan Children's Hospital and Institute of Child Health, Dhaka, Bangladesh
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11
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Robinson CH, Jeyakumar N, Luo B, Askenazi D, Deep A, Garg AX, Goldstein S, Greenberg JH, Mammen C, Nash DM, Parekh RS, Silver SA, Thabane L, Wald R, Zappitelli M, Chanchlani R. Long-Term Kidney Outcomes after Pediatric Acute Kidney Injury. J Am Soc Nephrol 2024; 35:1520-1532. [PMID: 39018120 PMCID: PMC11543010 DOI: 10.1681/asn.0000000000000445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 07/05/2024] [Indexed: 07/19/2024] Open
Abstract
Key Points Among 4173 children with AKI, 18% had major adverse kidney events (death, kidney failure, or CKD) during a median 10-year follow-up. AKI survivors were at 2–4 times higher risk of major adverse kidney events, hypertension, and subsequent AKI versus matched hospitalized comparators. This justifies improved surveillance after pediatric AKI to detect CKD and hypertension early and improve long-term kidney health. Background AKI is common in hospitalized children. Pediatric AKI receiving acute KRT is associated with long-term CKD, hypertension, and death. We aim to determine the outcomes after AKI in children who did not receive acute KRT because these remain uncertain. Methods Retrospective cohort study of all hospitalized children (0–18 years) surviving AKI without acute KRT between 1996 and 2020 in Ontario, Canada, identified by validated diagnostic codes in provincial administrative health databases. Children with prior KRT, CKD, or AKI were excluded. Cases were matched with up to four hospitalized comparators without AKI by age, neonatal status, sex, intensive care unit admission, cardiac surgery, malignancy, hypertension, hospitalization era, and a propensity score for AKI. Patients were followed until death, provincial emigration, or censoring in March 2021. The primary outcome was long-term major adverse kidney events (a composite of all-cause mortality, long-term KRT, or incident CKD). Results We matched 4173 pediatric AKI survivors with 16,337 hospitalized comparators. Baseline covariates were well-balanced following propensity score matching. During a median 9.7-year follow-up, 18% of AKI survivors developed long-term major adverse kidney event versus 5% of hospitalized comparators (hazard ratio [HR], 4.0; 95% confidence interval [CI], 3.6 to 4.4). AKI survivors had higher rates of long-term KRT (2% versus <1%; HR, 11.7; 95% CI, 7.5 to 18.4), incident CKD (16% versus 2%; HR, 7.9; 95% CI, 6.9 to 9.1), incident hypertension (17% versus 8%; HR, 2.3; 95% CI, 2.1 to 2.6), and AKI during subsequent hospitalization (6% versus 2%; HR, 3.7; 95% CI, 3.1 to 4.5), but no difference in all-cause mortality (3% versus 3%; HR, 0.9; 95% CI, 0.7 to 1.1). Conclusions Children surviving AKI without acute KRT were at higher long-term risk of CKD, long-term KRT, hypertension, and subsequent AKI versus hospitalized comparators.
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Affiliation(s)
- Cal H. Robinson
- Division of Paediatric Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Nivethika Jeyakumar
- ICES, Toronto, Ontario, Canada
- Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada
- London Health Sciences Centre, London, Ontario, Canada
| | - Bin Luo
- ICES, Toronto, Ontario, Canada
- Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada
- London Health Sciences Centre, London, Ontario, Canada
| | - David Askenazi
- Division of Pediatric Nephrology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
| | - Akash Deep
- Paediatric Intensive Care Unit, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Amit X. Garg
- ICES, Toronto, Ontario, Canada
- Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada
- London Health Sciences Centre, London, Ontario, Canada
| | - Stuart Goldstein
- Center for Acute Care Nephrology, Cincinnati Children's Hospital, Cincinnati, Ohio
| | - Jason H. Greenberg
- Division of Nephrology, Department of Pediatrics, Yale University, New Haven, Connecticut
| | - Cherry Mammen
- Division of Nephrology, Department of Pediatrics, University of British Columbia, Vancouver British Columbia, Canada
| | - Danielle M. Nash
- ICES, Toronto, Ontario, Canada
- Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada
- London Health Sciences Centre, London, Ontario, Canada
| | - Rulan S. Parekh
- Division of Paediatric Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Department of Medicine, Women's College Hospital and University of Toronto, Toronto, Ontario, Canada
| | - Samuel A. Silver
- Division of Nephrology, Kingston Health Sciences Centre, Queen's University, Kingston, Ontario, Canada
| | - Lehana Thabane
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Biostatistics Unit, St Joseph's Healthcare, Hamilton, Ontario, Canada
- Division of Pediatric Nephrology, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Ron Wald
- Division of Nephrology, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada
| | - Michael Zappitelli
- Division of Paediatric Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Rahul Chanchlani
- ICES, Toronto, Ontario, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Division of Pediatric Nephrology, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
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12
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Ashruf OS, Ashruf Z, Luyckx V, Kaelber DC, Sethi SK, Raina R. Sociodemographic Disparities in 1-Year Outcomes of Children With Community-Acquired Acute Kidney Injury. JAMA Netw Open 2024; 7:e2440988. [PMID: 39470639 PMCID: PMC11522937 DOI: 10.1001/jamanetworkopen.2024.40988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 08/27/2024] [Indexed: 10/30/2024] Open
Abstract
Importance Racial disparities have been identified in pediatric community-acquired acute kidney injury (CA-AKI), and they are associated with increased risk of child mortality, morbidity, and progression of kidney disease. Objective To assess clinical outcomes at 1 year among children with CA-AKI, stratified by age, race, and ethnicity. Design, Setting, and Participants This retrospective cohort study is a population-based analysis of deidentified, aggregated electronic health record data collected by 61 large health care organizations from 2003 to 2023 and accessed through the TriNetX platform. Outcomes were assessed at 1 year after a CA-AKI episode. Participants included pediatric patients (aged <18 years) with AKI. Data were accessed in January 2024. Exposure A diagnosis of CA-AKI and sociodemographic factors such as race, ethnicity, and age, as reported in electronic health records. Main Outcomes and Measures The primary end point of this study was to assess differences in clinical outcomes within 1 year of an episode of CA-AKI, including all-cause emergency department (ED) visits, intensive care unit (ICU) admissions, mechanical intubation and ventilation, and mortality. Risk was compared between White children and Asian (including Asian, Native Hawaiian, and Other Pacific Islander), Black, and Hispanic children, stratified by age group. Measures of association, Cox proportional hazard analyses, and Kaplan-Meier survival curves were performed within the TriNetX Advanced Analytics Platform between racial and ethnic groups for each analysis. Results From the total sample of 18 152 children, those with hospital-acquired AKI, chronic kidney disease, end-stage kidney failure, or dialysis dependence were excluded, leaving a final cohort of 17 125 children (mean [SD] age, 11.2 [5.2] years; 9424 male [55.3%]). Eligible patients were divided into racial and ethnic groups as follows: non-Hispanic Asian, 1169 children (6.5%); non-Hispanic Black, 4636 children (27.3%); Hispanic, 1786 children (10.2%); and non-Hispanic White, 9534 children (55.9%). Patients were further subdivided into groups aged 0 to 9 years (546 Asian children, 1675 Black children, 689 Hispanic children, and 3340 White children) and 10 to 18 years (623 Asian children, 2961 Black children, 1091 Hispanic children, and 6104 White children). Within 1 year of CA-AKI diagnosis, compared with White children, Black children experienced greater rates of ED visits (hazard ratio [HR], 1.53; 95% CI, 1.40-1.67), ICU admissions (HR, 1.31; 95% CI, 1.16-1.47), mechanical ventilation (HR, 1.33; 95% CI, 1.13-1.56), and all-cause mortality (HR, 1.27; 95% CI, 1.09-1.48), as well as the greatest risk for composite outcomes (HR, 1.43; 95% CI, 1.33-1.53). Hispanic children experienced greater rates of ED visits (HR, 1.40; 95% CI, 1.21-1.62) and the greatest risk of all-cause mortality (HR, 1.66; 95% CI, 1.31-2.09), whereas Asian children experienced greater rates of mechanical ventilation (HR, 1.69; 95% CI, 1.26-2.27), compared with White children. Black and Hispanic children aged 0 to 9 years were at greatest risk of experiencing poor clinical outcomes. Black children had a 11.41% lower survival probability and Hispanic children had a 7.14% lower survival probability compared with White children after an initial ED encounter. Conclusions and Relevance Among children with an identified episode of CA-AKI diagnosed in an ED, within 1 year, Black and Hispanic children had a poorer survival probability compared with White children. Future studies are needed to understand these disparities and improve awareness and follow-up after emergency care.
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Affiliation(s)
- Omer S. Ashruf
- Department of Internal Medicine, Northeast Ohio Medical University, Rootstown
| | - Zaid Ashruf
- Department of Nephrology, Akron Nephrology Associates, Cleveland Clinic Akron General Medical Center, Akron, Ohio
| | - Valerie Luyckx
- Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Public and Global Health, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
- Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa
| | - David C. Kaelber
- Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, Ohio
- Department of Internal Medicine, Case Western Reserve University, Cleveland, Ohio
- Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio
| | - Sidharth K. Sethi
- Pediatric Nephrology, Kidney Institute and Pediatric Intensive Care, Medanta, The Medicity Hospital, Gurgaon, Haryana, India
| | - Rupesh Raina
- Department of Nephrology, Akron Nephrology Associates, Cleveland Clinic Akron General Medical Center, Akron, Ohio
- Department of Nephrology, Akron Children’s Hospital, Akron, Ohio
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13
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Pournasiri Z, Bakhtiary M, Nikparast A, Hashemi SM, Narjes Ahmadizadeh S, Behzad A, Asghari G. The association between nutritional status measured by body mass index and outcomes in the pediatric intensive care unit. Front Pediatr 2024; 12:1421155. [PMID: 39355651 PMCID: PMC11443694 DOI: 10.3389/fped.2024.1421155] [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: 04/21/2024] [Accepted: 07/30/2024] [Indexed: 10/03/2024] Open
Abstract
Aim/Introduction The relationship between nutritional status upon admission to a pediatric intensive care unit (PICU) and clinical outcomes remains unclear. We examined the relationship between nutrition status, as indicated by body mass index-for-age (BMI-for-age), and clinical outcomes in the PICU. Method In this retrospective study at a tertiary care center, records of 1,015 critically ill children and adolescents aged one month to 18 years old with available anthropometric parameters were included. The nutritional status upon admission was determined by calculating the BMI-for-age z-score using the WHO growth charts as the reference. The participants were categorized as underweight (BMI-for-age z-score < -2), normal weight (-2 ≤ BMI-for-age z-score ≤ +1), and overweight/obese (BMI-for-age z-score > +1). Multi-variate odds ratios (OR) with 95% confidence intervals (CI) were used to investigate the association between malnutrition (being underweight and overweight/obese) and odds of Prolonged PICU stay (≥7 days) and PICU mortality after controlling for descriptive characteristics, Glasgow Coma Scale score status, fluctuations in serum sodium, and acute kidney injury confounders. Results The proportions of patients in underweight, normal weight, and overweight/obese categories were 34.2%, 45.8%, and 20%, respectively. During the study period, 21.5% of patients had prolonged PICU stay, and 5.6% of patients in PICU died. Compared to normal-weight patients, underweight patients had higher odds of prolonged PICU stay (OR: 1.52; 95% CI: 1.05-2.22) and PICU mortality (OR: 2.12; 95% CI: 1.22-4.01). Age- and gender-stratified full-adjusted analysis showed that the increased odds of prolonged PICU stay remained significant among underweight boys and underweight individuals aged 5-19 years old. Furthermore, the increased odds of PICU mortality remained significant among underweight individuals aged 2-5 years old. However, being overweight or obese during PICU admission did not demonstrate a significant association with our outcomes in the total sample or subgroup analysis. Conclusion Our findings showed that PICU patients who were underweight had higher odds of prolonged PICU stay and PICU mortality than their normal-weight counterparts. This underscores the importance of closely monitoring underweight patients in the PICU upon admission in order to improve clinical outcomes.
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Affiliation(s)
- Zahra Pournasiri
- Pediatric Nehrology Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahsa Bakhtiary
- Pediatric Nephrology Research Center, Research Institute for Children's Health, Mofid Children's Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Ali Nikparast
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyedeh Masumeh Hashemi
- Pediatric Intensive Care Departmant, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyyedeh Narjes Ahmadizadeh
- Pediatric Intensive Care Departmant, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Behzad
- Pediatric Intensive Care Departmant, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Golaleh Asghari
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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14
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Ahn HC, Frymoyer A, Boothroyd DB, Bonifacio S, Sutherland SM, Chock VY. Acute kidney injury in neonates with hypoxic ischemic encephalopathy based on serum creatinine decline compared to KDIGO criteria. Pediatr Nephrol 2024; 39:2789-2796. [PMID: 38326648 DOI: 10.1007/s00467-024-06287-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 12/27/2023] [Accepted: 12/28/2023] [Indexed: 02/09/2024]
Abstract
BACKGROUND Neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia (HIE + TH) are at risk for acute kidney injury (AKI). The standardized Kidney Disease Improving Global Outcomes (KDIGO) criteria identifies AKI based on a rise in serum creatinine (SCr) or reduced urine output. This definition is challenging to apply in neonates given the physiologic decline in SCr during the first week of life. Gupta et al. proposed alternative neonatal criteria centered on rate of SCr decline. This study aimed to compare the rate of AKI based on KDIGO and Gupta in neonates with HIE and to examine associations with mortality and morbidity. METHODS A retrospective review was performed of neonates with moderate to severe HIE + TH from 2008 to 2020 at a single center. AKI was assessed in the first 7 days after birth by KDIGO and Gupta criteria. Mortality, brain MRI severity of injury, length of stay, and duration of respiratory support were compared between AKI groups. RESULTS Among 225 neonates, 64 (28%) met KDIGO, 69 (31%) neonates met Gupta but not KDIGO, and 92 (41%) did not meet either definition. Both KDIGO-AKI and GuptaOnly-AKI groups had an increased risk of the composite mortality and/or moderate/severe brain MRI injury along with longer length of stay and prolonged duration of respiratory support compared to those without AKI. CONCLUSIONS AKI in neonates with HIE + TH was common and varied by definition. The Gupta definition based on rate of SCr decline identified additional neonates not captured by KDIGO criteria who are at increased risk for adverse outcomes. Incorporating the rate of SCr decline into the neonatal AKI definition may increase identification of clinically relevant kidney injury in neonates with HIE + TH.
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Affiliation(s)
- Haejun C Ahn
- Division of Pediatric Nephrology, Stanford University School of Medicine, Palo Alto, CA, USA.
- Pediatric Nephrology, Swedish Health, Seattle, WA, USA.
| | - Adam Frymoyer
- Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Derek B Boothroyd
- Quantitative Sciences Unit, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Sonia Bonifacio
- Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Scott M Sutherland
- Division of Pediatric Nephrology, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Valerie Y Chock
- Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Palo Alto, CA, USA
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15
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Rivetti G, Gizzone P, Petrone D, Di Sessa A, Miraglia del Giudice E, Guarino S, Marzuillo P. Acute Kidney Injury in Children: A Focus for the General Pediatrician. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1004. [PMID: 39201939 PMCID: PMC11352805 DOI: 10.3390/children11081004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 07/31/2024] [Accepted: 08/13/2024] [Indexed: 09/03/2024]
Abstract
Acute kidney injury (AKI) presents significant challenges in pediatric care, often remaining underrecognized. This paper provides an overview of pediatric AKI, highlighting its epidemiology, pathophysiology, diagnosis, predisposing conditions, and treatment. AKI in children stems from diverse causes, including renal tubular damage, vasoconstriction, and inflammation. Diagnosis relies on traditional markers such as serum creatinine and urine output, alongside emerging biomarkers such as Cystatin C, NGAL, KIM-1, IL-18, TIMP-2 and IGFBP7, urinary calprotectin, URBP4, L-FABP, and clusterin. Various pediatric conditions predispose to AKI, including type 1 diabetes, pneumonia, bronchiolitis, appendicitis, gastroenteritis, COVID-19, multisystem inflammatory syndrome, sickle cell disease, and malignancies. Treatment entails supportive care with fluid management and, in severe cases, renal replacement therapy. Timely recognition and management are essential to mitigating adverse outcomes. Enhanced awareness and integration of novel biomarkers could improve pediatric AKI care, warranting further research for better diagnosis and management.
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Affiliation(s)
| | | | | | | | | | | | - Pierluigi Marzuillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Via Luigi de Crecchio 2, 80138 Naples, Italy; (G.R.); (P.G.); (D.P.); (A.D.S.); (E.M.d.G.); (S.G.)
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16
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Lakat T, Fekete A, Demeter K, Toth AR, Varga ZK, Patonai A, Kelemen H, Budai A, Szabo M, Szabo AJ, Kaila K, Denes A, Mikics E, Hosszu A. Perinatal asphyxia leads to acute kidney damage and increased renal susceptibility in adulthood. Am J Physiol Renal Physiol 2024; 327:F314-F326. [PMID: 38932694 DOI: 10.1152/ajprenal.00039.2024] [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: 02/06/2024] [Revised: 05/23/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024] Open
Abstract
Perinatal asphyxia (PA) poses a significant threat to multiple organs, particularly the kidneys. Diagnosing PA-associated kidney injury remains challenging, and treatment options are inadequate. Furthermore, there is a lack of long-term follow-up data regarding the renal implications of PA. In this study, 7-day-old male Wistar rats were exposed to PA using a gas mixture (4% O2; 20% CO2 in N2 for 15 min) to investigate molecular pathways linked to renal tubular damage, hypoxia, angiogenesis, heat shock response, inflammation, and fibrosis in the kidney. In a second experiment, adult rats with a history of PA were subjected to moderate renal ischemia-reperfusion (IR) injury to test the hypothesis that PA exacerbates renal susceptibility. Our results revealed an increased gene expression of renal injury markers (kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin), hypoxic and heat shock factors (hypoxia-inducible factor-1α, heat shock factor-1, and heat shock protein-27), proinflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1), and fibrotic markers (transforming growth factor-β, connective tissue growth factor, and fibronectin) promptly after PA. Moreover, a machine learning model was identified through random forest analysis, demonstrating an impressive classification accuracy (95.5%) for PA. Post-PA rats showed exacerbated functional decline and tubular injury and more intense hypoxic, heat shock, proinflammatory, and profibrotic response after renal IR injury compared with controls. In conclusion, PA leads to subclinical kidney injury, which may increase the susceptibility to subsequent renal damage later in life. In addition, the parameters identified through random forest analysis provide a robust foundation for future biomarker research in the context of PA.NEW & NOTEWORTHY This article demonstrates that perinatal asphyxia leads to subclinical kidney injury that permanently increases renal susceptibility to subsequent ischemic injury. We identified major molecular pathways involved in perinatal asphyxia-induced renal complications, highlighting potential targets of therapeutic approaches. In addition, random forest analysis revealed a model that classifies perinatal asphyxia with 95.5% accuracy that may provide a strong foundation for further biomarker research. These findings underscore the importance of multiorgan follow-up for perinatal asphyxia-affected patients.
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Affiliation(s)
- Tamas Lakat
- MTA-SE Lendület "Momentum" Diabetes Research Group, Budapest, Hungary
- Pediatric Center, Semmelweis University, Budapest, Hungary
| | - Andrea Fekete
- MTA-SE Lendület "Momentum" Diabetes Research Group, Budapest, Hungary
- Pediatric Center, Semmelweis University, Budapest, Hungary
| | - Kornel Demeter
- Behavioral Studies Unit, HUN-REN Institute of Experimental Medicine, Budapest, Hungary
| | - Akos R Toth
- MTA-SE Lendület "Momentum" Diabetes Research Group, Budapest, Hungary
- Pediatric Center, Semmelweis University, Budapest, Hungary
| | - Zoltan K Varga
- Translational Behavioral Neuroscience Research Group, HUN-REN Institute of Experimental Medicine, Budapest, Hungary
| | - Attila Patonai
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary
| | - Hanga Kelemen
- Translational Behavioral Neuroscience Research Group, HUN-REN Institute of Experimental Medicine, Budapest, Hungary
| | - Andras Budai
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Miklos Szabo
- Pediatric Center, Semmelweis University, Budapest, Hungary
| | - Attila J Szabo
- Pediatric Center, Semmelweis University, Budapest, Hungary
| | - Kai Kaila
- Molecular and Integrative Biosciences Research Programme, Neuroscience Center (HiLIFE), University of Helsinki, Helsinki, Finland
| | - Adam Denes
- Laboratory of Neuroimmunology, HUN-REN Institute of Experimental Medicine, Budapest, Hungary
| | - Eva Mikics
- Translational Behavioral Neuroscience Research Group, HUN-REN Institute of Experimental Medicine, Budapest, Hungary
| | - Adam Hosszu
- MTA-SE Lendület "Momentum" Diabetes Research Group, Budapest, Hungary
- Pediatric Center, Semmelweis University, Budapest, Hungary
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17
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Alghamdi FA, Bin Mahfooz MA, Almutairi HF, Alshaiban NS, Alotibi KE, Kabbani OM, Kabbani MS. Incidence, Risk Factors and Outcomes of Acute Kidney Injury in Neonates Undergoing Open-heart Surgeries: Single Center Experience. J Saudi Heart Assoc 2024; 36:70-78. [PMID: 38919507 PMCID: PMC11195661 DOI: 10.37616/2212-5043.1374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 04/12/2024] [Accepted: 04/14/2024] [Indexed: 06/27/2024] Open
Abstract
Background Incidence and outcomes of acute kidney injury (AKI) among neonates who underwent open-heart surgery are not well highlighted in the literature. We aim to assess the incidence, risk factors, and outcome of AKI among neonates undergoing open-heart surgery. Methods This is a retrospective cohort study between 2016 and 2021 for all neonates requiring open heart surgery. The cases were divided into 2 groups: the AKI (index) group and the non-AKI (control) group. The two groups were statistically compared for risk factors, needs for dialysis, and outcomes. Results 100 patients fulfilled the inclusion criteria. Among them, 74 (74%) developed AKI, including 41 (55%), 15 (21%), and 18 (24%) patients in KDIGO stages 1, 2, and 3, respectively. Multivariate analysis comparing both groups demonstrated that low pre-operative creatinine (p = 0.01), prolonged bypass time (p = 0.0004) and high vasoactive inotropic score (VIS), (p = 0.0008) were risk factors for developing AKI post-operatively. Furthermore, in the AKI group, 17 (23%) neonates required renal replacement therapy in the form of peritoneal dialysis. The length of stay was higher in the AKI index group (p = 0.015). Patients who had AKI recovered their kidney function at discharge. There was no difference in mortality between both groups. Conclusion The AKI occurred in 74% of neonates undergoing open-heart surgery, with 23% of them needing peritoneal dialysis. Low pre-operative creatinine, high VIS score, and prolonged bypass time are potential risk factors for AKI development after neonatal open-heart surgery. AKI may lead to prolonged hospitalization, though most affected patients recovered their normal kidney function at discharge.
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Affiliation(s)
- Faisal A. Alghamdi
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh,
Saudi Arabia
| | | | - Hatim F. Almutairi
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh,
Saudi Arabia
| | - Nasser S. Alshaiban
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh,
Saudi Arabia
| | - Khaled E. Alotibi
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh,
Saudi Arabia
| | - Omar M. Kabbani
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh,
Saudi Arabia
| | - Mohamed S. Kabbani
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh,
Saudi Arabia
- King Abdullah International Medical Research Centre (KAIMRC), Riyadh,
Saudi Arabia
- Department of Cardiac Science, Ministry of National Guard Health Affairs, Riyadh,
Saudi Arabia
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18
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Patel M, Hornik C, Diamantidis C, Selewski DT, Gbadegesin R. A reappraisal of risk factors for hypertension after pediatric acute kidney injury. Pediatr Nephrol 2024; 39:1599-1605. [PMID: 37987863 PMCID: PMC10947822 DOI: 10.1007/s00467-023-06222-3] [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: 09/15/2023] [Revised: 10/16/2023] [Accepted: 10/27/2023] [Indexed: 11/22/2023]
Abstract
BACKGROUND Acute kidney injury (AKI) is common in hospitalized children and increases the risk of chronic kidney disease (CKD) and hypertension, but little is known about the patient level risk factors for pediatric hypertension after AKI. The aims of this study are to evaluate the prevalence and risk factors for new onset hypertension in hospitalized children with AKI and to better understand the role of acute kidney disease (AKD) in the development of hypertension. METHODS This study was an observational cohort of all children ≤ 18 years old admitted to a single tertiary care children's hospital from 2015 to 2019 with a diagnosis of AKI. Hypertension was defined as blood pressure > 95th percentile for sex, age, height, diagnosis of hypertension on the problem list, or prescription of antihypertensive medication for > 90 days after AKI. RESULTS A total of 410 children were included in the cohort. Of these, 78 (19%) developed hypertension > 90 days after AKI. A multivariable logistic regression model identified AKD, need for kidney replacement therapy, congenital heart disease, and non-kidney solid organ transplantation as risk factors for hypertension after AKI. CONCLUSIONS Incident hypertension after 3 months is common among hospitalized children with AKI, and AKD, need for dialysis, congenital heart disease, and non-kidney solid organ transplant are significant risk factors for hypertension after AKI. Monitoring for hypertension development in these high-risk children is critical to mitigate long-term adverse kidney and cardiovascular outcomes.
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Affiliation(s)
- Mital Patel
- Department of Pediatrics, Section of Nephrology, Wake Forest School of Medicine and Brenner Children's Hospital, Winston Salem, NC, USA.
| | - Christoph Hornik
- Division of Critical Care Medicine, Department of Pediatrics and Duke Clinical Research Institute, Duke University, Durham, NC, USA
| | - Clarissa Diamantidis
- Division of Nephrology, Department of Medicine, Duke University, Durham, NC, USA
| | - David T Selewski
- Division of Pediatric Nephrology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA
| | - Rasheed Gbadegesin
- Division of Nephrology, Department of Pediatrics, Duke University, Durham, NC, USA
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19
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Harris RE, Yates AR, Nandi D, Krawczeski CD, Klamer B, Martinez GV, Andrade GM, Beckman BF, Bi J, Zepeda-Orozco D. Urinary biomarkers associated with acute kidney injury in pediatric mechanical circulatory support patients. Pediatr Nephrol 2024; 39:569-577. [PMID: 37552466 DOI: 10.1007/s00467-023-06089-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 07/02/2023] [Accepted: 07/03/2023] [Indexed: 08/09/2023]
Abstract
BACKGROUND In patients requiring mechanical circulatory support (MCS), the incidence of acute kidney injury (AKI) is between 37 and 63%. In this study, we performed an exploratory analysis evaluating the relationship of multiple urine biomarkers with AKI development in pediatric MCS patients. METHODS This is a single center retrospective study in a pediatric cohort receiving MCS from August 2014 to November 2020. We measured 14 urine biomarkers of kidney injury on day 1 following MCS initiation and analyzed their association with development of AKI in the first 7 days of MCS initiation. RESULTS Sixty patients met inclusion criteria. Patients with AKI were more likely to be supported by venoarterial extracorporeal membrane oxygenation (65% vs. 8.3%, p < 0.001), compared to the no AKI group and less likely to have ventricular assist devices (10% vs. 50%, p < 0.001). There was a significant increase in the median urine albumin and urine osteoactivin in the AKI group, compared to the no AKI group (p = 0.020 and p = 0.018, respectively). When normalized to urine creatinine (UCr), an increased log osteoactivin/UCr was associated with higher odds of AKI development (OR: 2.05; 95% CI: 1.07, 4.44; p = 0.028), and higher log epidermal growth factor (EGF)/UCr (OR: 0.41; 95% CI: 0.15, 0.96) was associated with decreased odds of AKI. CONCLUSIONS Early increase in urine osteoactivin is associated with AKI development within 7 days of MCS initiation in pediatric patients. Contrary, an increased urine EGF is associated with kidney protection. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Rachel E Harris
- Division of Pediatric Cardiology, Nationwide Children's Hospital, Columbus, OH, USA.
| | - Andrew R Yates
- Division of Pediatric Cardiology, Nationwide Children's Hospital, Columbus, OH, USA
- Division of Pediatric Critical Care Medicine, Nationwide Children's Hospital, Columbus, OH, USA
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Deipanjan Nandi
- Division of Pediatric Cardiology, Nationwide Children's Hospital, Columbus, OH, USA
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Catherine D Krawczeski
- Division of Pediatric Cardiology, Nationwide Children's Hospital, Columbus, OH, USA
- Division of Pediatric Critical Care Medicine, Nationwide Children's Hospital, Columbus, OH, USA
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Brett Klamer
- Biostatistics Resource at Nationwide Children's Hospital, Columbus, OH, USA
| | - Gabriela Vasquez Martinez
- Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's, Columbus, OH, USA
| | - Gabriel Mayoral Andrade
- Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's, Columbus, OH, USA
| | - Brian F Beckman
- Division of Pediatric Cardiology, Nationwide Children's Hospital, Columbus, OH, USA
- Center for Cardiovascular Research, Nationwide Children's Hospital, Columbus, OH, USA
| | - Jianli Bi
- Division of Pediatric Cardiology, Nationwide Children's Hospital, Columbus, OH, USA
- Center for Cardiovascular Research, Nationwide Children's Hospital, Columbus, OH, USA
| | - Diana Zepeda-Orozco
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
- Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's, Columbus, OH, USA
- Division of Nephrology and Hypertension, Nationwide Children's Hospital, Columbus, OH, USA
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20
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Persson I, Grünwald A, Morvan L, Becedas D, Arlbrandt M. A Machine Learning Algorithm Predicting Acute Kidney Injury in Intensive Care Unit Patients (NAVOY Acute Kidney Injury): Proof-of-Concept Study. JMIR Form Res 2023; 7:e45979. [PMID: 38096015 PMCID: PMC10755657 DOI: 10.2196/45979] [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: 02/02/2023] [Revised: 10/08/2023] [Accepted: 10/26/2023] [Indexed: 12/31/2023] Open
Abstract
BACKGROUND Acute kidney injury (AKI) represents a significant global health challenge, leading to increased patient distress and financial health care burdens. The development of AKI in intensive care unit (ICU) settings is linked to prolonged ICU stays, a heightened risk of long-term renal dysfunction, and elevated short- and long-term mortality rates. The current diagnostic approach for AKI is based on late indicators, such as elevated serum creatinine and decreased urine output, which can only detect AKI after renal injury has transpired. There are no treatments to reverse or restore renal function once AKI has developed, other than supportive care. Early prediction of AKI enables proactive management and may improve patient outcomes. OBJECTIVE The primary aim was to develop a machine learning algorithm, NAVOY Acute Kidney Injury, capable of predicting the onset of AKI in ICU patients using data routinely collected in ICU electronic health records. The ultimate goal was to create a clinical decision support tool that empowers ICU clinicians to proactively manage AKI and, consequently, enhance patient outcomes. METHODS We developed the NAVOY Acute Kidney Injury algorithm using a hybrid ensemble model, which combines the strengths of both a Random Forest (Leo Breiman and Adele Cutler) and an XGBoost model (Tianqi Chen). To ensure the accuracy of predictions, the algorithm used 22 clinical variables for hourly predictions of AKI as defined by the Kidney Disease: Improving Global Outcomes guidelines. Data for algorithm development were sourced from the Massachusetts Institute of Technology Lab for Computational Physiology Medical Information Mart for Intensive Care IV clinical database, focusing on ICU patients aged 18 years or older. RESULTS The developed algorithm, NAVOY Acute Kidney Injury, uses 4 hours of input and can, with high accuracy, predict patients with a high risk of developing AKI 12 hours before onset. The prediction performance compares well with previously published prediction algorithms designed to predict AKI onset in accordance with Kidney Disease: Improving Global Outcomes diagnosis criteria, with an impressive area under the receiver operating characteristics curve (AUROC) of 0.91 and an area under the precision-recall curve (AUPRC) of 0.75. The algorithm's predictive performance was externally validated on an independent hold-out test data set, confirming its ability to predict AKI with exceptional accuracy. CONCLUSIONS NAVOY Acute Kidney Injury is an important development in the field of critical care medicine. It offers the ability to predict the onset of AKI with high accuracy using only 4 hours of data routinely collected in ICU electronic health records. This early detection capability has the potential to strengthen patient monitoring and management, ultimately leading to improved patient outcomes. Furthermore, NAVOY Acute Kidney Injury has been granted Conformite Europeenne (CE)-marking, marking a significant milestone as the first CE-marked AKI prediction algorithm for commercial use in European ICUs.
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Affiliation(s)
- Inger Persson
- Department of Statistics, Uppsala University, Uppsala, Sweden
- AlgoDx AB, Stockholm, Sweden
| | | | | | | | - Martin Arlbrandt
- Department of Anaesthesiology and Intensive Care, Södersjukhuset (Stockholm South General Hospital), Stockholm, Sweden
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21
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M’hango H, Kabengele C, Sukuntu V, Mwaba C. Burden and Risk Factors of Contrast-Associated Acute Kidney Injury in Hospitalized Zambian Children: A Prospective Cohort Study at the University Teaching Hospitals. Can J Kidney Health Dis 2023; 10:20543581231205156. [PMID: 37885671 PMCID: PMC10599111 DOI: 10.1177/20543581231205156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 08/09/2023] [Indexed: 10/28/2023] Open
Abstract
Background Contrast-associated acute kidney injury (CAAKI) is defined as acute kidney injury (AKI) occurring within 72 hours of administration of contrast media (CM) and is linked to adverse outcomes including longer hospital stay, increased hospital mortality, and a higher risk of chronic kidney disease in later life. Risk factors for the development of CAAKI in the Zambian pediatric population have not been well studied. Objectives The objective of this study was to assess the burden of CAAKI, ascertain its risk factors, and describe short-term outcomes in hospitalized children at the University Teaching Hospitals (UTH) undergoing contrast-enhanced radiological investigations. Methods This was a prospective observational study of in-patients undergoing contrast-enhanced radiological procedures, between September 2020 and September 2021. The participants were recruited from the Children's Hospital, the Cancer Diseases Hospital, and the Pediatric Surgical Ward at the University Teaching Hospital in Lusaka, Zambia. The primary outcome variable was occurrence of AKI at 48 hours post CM administration. We used 2 criteria to define CAAKI in our study-the European Society of Urogenital Radiology (ESUR) and the Kidney Disease Improving Global Outcomes (KDIGO) 2012 criteria. Multivariable logistic regression models were formulated to assess for risk factors of CAAKI. Results Of the 201 enrolled participants, 123 (61.2%) were male and the median age of the participants was 5 years (interquartile range [IQR] = 3-10). The mean hemoglobin was 103 g/L (standard deviation [SD] = 26), median creatinine was 30.9 µmol/l (IQR = 22.6-43), and the glomerular filtration rate (GFR) was 102.5 mL/min/1.73 m2 (IQR = 76.2-129.4). Forty-six (22.9%) developed CAAKI using the ESUR compared with 4.5% (9/201) using the KDIGO criteria. Independent risk factors of CAAKI were receiving a higher dose of CM (adjusted odds ratio [aOR] = 2.54; 95% confidence interval [CI] = [1.12-5.74]), prematurity (aOR = 4.6; 95% CI = [1.05-16.7]), and a higher eGFR (aOR= 1.01; 95% CI = [1.01-1.02]). Females had higher odds of CAAKI (aOR = 2.48; 95% CI = [1.18-5.18]) when compared with males. One CAAKI participant (2.2%) died; none of the participants who developed CAAKI and survived required dialysis and most of them (90%) were discharged before day 7. Day 7 eGFR results had returned to or near baseline values for those whose creatinine results were available. Conclusions Using the ESUR criteria, a significant proportion (22.9%) of children undergoing contrast-enhanced computed tomography (CT) scans at the UTH developed CAAKI. In contrast, using the KDIGO criteria only 4.5% had CAAKI. Being born as a preterm baby, being female, having a higher eGFR at baseline, and receiving a higher dose of CM were found to be independent risk factors for CAAKI development in Zambian children. Most of the cases of CAAKI in children were transient and of little clinical significance as only a minority of patients developing CAAKI required kidney replacement therapy and all resolved by day 7 post administration of CM.
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Affiliation(s)
- Hellen M’hango
- Department of Paediatrics, University Teaching Hospitals – Children’s Hospital, Lusaka, Zambia
| | | | - Veronica Sukuntu
- Department of Radiology, University Teaching Hospitals – Adult Hospital, Lusaka, Zambia
| | - Chisambo Mwaba
- Department of Paediatrics, University Teaching Hospitals – Children’s Hospital, Lusaka, Zambia
- Department of Paediatrics and Child Health, School of Medicine, University of Zambia, Lusaka, Zambia
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22
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Raina R, Sethi S, Aitharaju V, Vadhera A, Haq I. Epidemiology data on the cost and outcomes associated with pediatric acute kidney injury. Pediatr Res 2023; 94:1385-1391. [PMID: 36949285 DOI: 10.1038/s41390-023-02564-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 02/14/2023] [Accepted: 02/21/2023] [Indexed: 03/24/2023]
Abstract
BACKGROUND Hospitalized children with acute kidney injury (AKI) have not been extensively studied for clinical outcomes including hospital stay, the need for mechanical ventilation, mortality rates, and healthcare utilization. We hypothesize significant financial costs and increased morbidity and mortality associated with pediatric AKI. METHODS This is a retrospective study of pediatric patients (age ≤18 years) included in the Kids' Inpatient Database (KID) between January 1, 2016, and December 31, 2021. The results of the data analysis were utilized for comparative testing between the AKI and non-AKI cohorts. RESULTS The study included 4842 children [with AKI (n = 2424) and without AKI (n = 2418)]. The odds of mortality (p = 0.004) and mechanical ventilation (p < 0.001) were observed to be significantly higher among those with AKI as compared to those without AKI. Additionally, the median (IQR) duration of stay in the hospital (p < 0.001) and total cost (p < 0.001) were significantly higher among those with AKI vs. those without AKI. CONCLUSIONS AKI in children was associated with higher odds of mortality, longer duration of hospital stay, increased requirement of mechanical ventilation, and increased hospital expenditure. The scientific community can utilize this information to better understand the outcomes associated with this disease process in this patient population. IMPACT This article has thoroughly evaluated epidemiologic data associated with pediatric acute kidney injury (AKI) in hospitalized patients This study assesses mortality, hospital expenditure, and other factors to strengthen single-center and few multi-center studies and provides novel data regarding insurance and cost associated with pediatric AKI With increased knowledge of current epidemiology and risk factors, the scientific community can better understand prevention and outcomes in hospitalized children with AKI.
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Affiliation(s)
- Rupesh Raina
- Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA.
- Department of Nephrology, Akron Children's Hospital, Akron, OH, USA.
| | - Sidharth Sethi
- Pediatric Nephrology, Kidney Institute and Pediatric Intensive Care, Medanta, The Medicity Hospital, Gurgaon, Haryana, 122001, India
| | - Varun Aitharaju
- Department of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA
| | | | - Imad Haq
- Department of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA
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23
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Patel M, Hornik C, Diamantidis C, Selewski DT, Gbadegesin R. Patient level factors increase risk of acute kidney disease in hospitalized children with acute kidney injury. Pediatr Nephrol 2023; 38:3465-3474. [PMID: 37145183 PMCID: PMC10530194 DOI: 10.1007/s00467-023-05997-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 04/18/2023] [Accepted: 04/19/2023] [Indexed: 05/06/2023]
Abstract
BACKGROUND Studies in adults have shown that persistent kidney dysfunction ≥7-90 days following acute kidney injury (AKI), termed acute kidney disease (AKD), increases chronic kidney disease (CKD) and mortality risk. Little is known about the factors associated with the transition of AKI to AKD and the impact of AKD on outcomes in children. The aim of this study is to evaluate risk factors for progression of AKI to AKD in hospitalized children and to determine if AKD is a risk factor for CKD. METHODS Retrospective cohort study of children age ≤18 years admitted with AKI to all pediatric units at a single tertiary-care children's hospital between 2015 and 2019. Exclusion criteria included insufficient serum creatinine values to evaluate for AKD, chronic dialysis, or previous kidney transplant. RESULTS A total of 528 children with AKI were included in the study. There were 297 (56.3%) hospitalized AKI survivors who developed AKD. Among children with AKD, 45.5% developed CKD compared to 18.7% in the group without AKD (OR 4.0, 95% CI 2.1-7.4, p-value <0.001 using multivariable logistic regression analysis including other covariates). Multivariable logistic regression model identified age at AKI diagnosis, PCICU and NICU admission, prematurity, malignancy, bone marrow transplant, previous AKI, mechanical ventilation, AKI stage, duration of kidney injury, and need for kidney replacement therapy during day 1-7 as risk factors for AKD after AKI. CONCLUSIONS AKD is common among hospitalized children with AKI and multiple risk factors are associated with AKD. Children that progress from AKI to AKD are at higher risk of developing CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Mital Patel
- Division of Nephrology, Department of Pediatrics, Duke University, Durham, NC, USA.
| | - Christoph Hornik
- Division of Critical Care Medicine, Department of Pediatrics and Duke Clinical Research Institute, Duke University, Durham, NC, USA
| | - Clarissa Diamantidis
- Division of Nephrology, Department of Medicine, Duke University, Durham, NC, USA
| | - David T Selewski
- Division of Pediatric Nephrology, Department of Pediatrics, Medical University of South Carolina Charleston, Charleston, SC, USA
| | - Rasheed Gbadegesin
- Division of Nephrology, Department of Pediatrics, Duke University, Durham, NC, USA
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24
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Keneni M, Murugan R, Bizuwork K, Asfaw T, Tekle S, Tolosa G, Desalew A. Risk factors associated with acute kidney injury in a pediatric intensive care unit in Addis Ababa Ethiopia: case-control study. BMC Nephrol 2023; 24:279. [PMID: 37735373 PMCID: PMC10514953 DOI: 10.1186/s12882-023-03322-y] [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: 10/27/2022] [Accepted: 09/05/2023] [Indexed: 09/23/2023] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a serious health problem in critically ill children. It is associated with poor treatment outcomes and high morbidity and mortality rates. Globally, one in three critically ill children suffers from acute kidney injury. However, limited data are available in Africa, particularly Ethiopia, which highlighting the risk factors related to acute kidney injury. Therefore, this study aimed to identify the risk factors associated with acute kidney injury among critically ill children admitted to the pediatric intensive care unit (PICU) at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. METHODS A facility-based unmatched case-control study was carried out on 253 (85 cases and 168 controls) critically ill children admitted to the pediatric intensive care unit from January 2011 to December 2021. Participants were selected using a systematic random sampling technique for the control group and all cases consecutively. Data were collected using a structured checklist. Data were entered using Epi data version 4.6 and analyzed using SPSS version 25. Multivariable analysis was carried out using the adjusted odds ratio (aOR) with a 95% confidence interval (CI) to identify associated factors with acute kidney injury. Statistical significance was set at P < 0.05. RESULTS The median age of the participants was two years. Approximately 55.6% of cases and 53.1% of controls were females. The diagnosis of hypertension (aOR = 5.36; 95% CI: 2.06-13.93), shock (aOR = 3.88, 95% CI: 1.85-8.12), exposure to nephrotoxic drugs (aOR = 4.09; 95% CI: 1. 45- 11.59), sepsis or infection aOR = 3.36; 95% CI: 1.42-7.99), nephritic syndrome (aOR = 2.97; 95% CI:1.19, 7.43), and use of mechanical ventilation aOR = 2.25, 95% CI: 1.12, 4.51) were significantly associated factors with acute kidney injury. CONCLUSION The diagnosis of sepsis or infection, hypertension, shock, nephrotoxic drugs, demand for mechanical ventilation support, and nephritic syndrome increased the risk of AKI among critically ill children. Multiple risk factors for AKI are associated with illness and severity. All measures that ensure adequate renal perfusion must be taken in critically ill children with identified risk factors to prevent the development of AKI.
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Affiliation(s)
- Mulualem Keneni
- School of Nursing and Midwifery, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Rajalakshmi Murugan
- School of Nursing and Midwifery, College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia
| | - Ketema Bizuwork
- School of Nursing and Midwifery, College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia
| | - Tesfaye Asfaw
- School of Nursing and Midwifery, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Sosina Tekle
- School of Nursing and Midwifery, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Gadissa Tolosa
- School of Nursing and Midwifery, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Assefa Desalew
- School of Nursing and Midwifery, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia.
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25
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Mai DH, Sutherland S, Blinder J, Hollander SA. A novel acute kidney injury scoring system for renal and clinical outcomes in pediatric heart transplant patients. Pediatr Transplant 2023; 27:e14565. [PMID: 37409513 DOI: 10.1111/petr.14565] [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: 04/18/2023] [Revised: 06/21/2023] [Accepted: 06/28/2023] [Indexed: 07/07/2023]
Abstract
BACKGROUND The development of acute kidney injury (AKI) has been associated with worse outcomes in children after heart transplantation. Our study compares the application of a cumulative six-point Kidney Diseases Improving Global Outcomes (KDIGO) AKI scoring system, utilizing both creatinine and urine output criteria that we term as the AKI-6 criteria, to traditional AKI staging as a predictor for clinical and renal outcomes in the pediatric heart transplant recipients. METHODS We conducted a retrospective single-center chart review on 155 pediatric patients who underwent heart transplantation from May 2014 to December 2021. The primary independent variable was the presence of severe AKI. Severe AKI by KDIGO was defined as Stage ≥2, whereas severe AKI by AKI-6 was defined as cumulative scores ≥4 or Stage 3 AKI based on either KDIGO criterion alone. Primary outcomes included actuarial survival and renal dysfunction by 1-year post-transplant, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 . RESULTS In total, 140 (90%) patients developed AKI; 98 (63%) patients developed severe AKI by KDIGO, and 60 (39%) by AKI-6. Severe AKI by AKI-6 was associated with worse actuarial survival following heart transplantation compared with KDIGO (p = 0.01). Of the 143 patients with 1-year creatinine data, 6 (11%) patients out of 54 with severe AKI by AKI-6 had evidence of renal dysfunction (p = 0.01), compared with 6 (7%) patients out of 88 by KDIGO (p = 0.3). CONCLUSIONS AKI-6 scoring provides greater prognostic utility for actuarial survival and renal dysfunction by 1-year post-heart transplantation in pediatric patients than traditional KDIGO staging.
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Affiliation(s)
- Daniel H Mai
- Stanford University School of Medicine, Palo Alto, California, USA
| | - Scott Sutherland
- Stanford University School of Medicine, Palo Alto, California, USA
| | - Joshua Blinder
- Stanford University School of Medicine, Palo Alto, California, USA
| | - Seth A Hollander
- Stanford University School of Medicine, Palo Alto, California, USA
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26
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Robinson CH, Iyengar A, Zappitelli M. Early recognition and prevention of acute kidney injury in hospitalised children. THE LANCET. CHILD & ADOLESCENT HEALTH 2023; 7:657-670. [PMID: 37453443 DOI: 10.1016/s2352-4642(23)00105-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 04/17/2023] [Accepted: 04/18/2023] [Indexed: 07/18/2023]
Abstract
Acute kidney injury is common in hospitalised children and is associated with poor patient outcomes. Once acute kidney injury occurs, effective therapies to improve patient outcomes or kidney recovery are scarce. Early identification of children at risk of acute kidney injury or at an early injury stage is essential to prevent progression and mitigate complications. Paediatric acute kidney injury is under-recognised by clinicians, which is a barrier to optimisation of inpatient care and follow-up. Acute kidney injury definitions rely on functional biomarkers (ie, serum creatinine and urine output) that are inadequate, since they do not account for biological variability, analytical issues, or physiological responses to volume depletion. Improved predictive tools and diagnostic biomarkers of kidney injury are needed for earlier detection. Novel strategies, including biomarker-guided care algorithms, machine-learning methods, and electronic alerts tied to clinical decision support tools, could improve paediatric acute kidney injury care. Clinical prediction models should be studied in different paediatric populations and acute kidney injury phenotypes. Research is needed to develop and test prevention strategies for acute kidney injury in hospitalised children, including care bundles and therapeutics.
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Affiliation(s)
- Cal H Robinson
- Division of Paediatric Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, The University of Toronto, Toronto, ON, Canada
| | - Arpana Iyengar
- Department of Paediatric Nephrology, St John's National Academy of Health Sciences, Bangalore, India
| | - Michael Zappitelli
- Division of Paediatric Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
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27
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de Fontnouvelle C, Zappitelli M, Thiessen-Philbrook HR, Jia Y, Kimmel PL, Kaufman JS, Devarajan P, Parikh CR, Greenberg JH. Biomarkers of eGFR decline after cardiac surgery in children: findings from the ASSESS-AKI study. Pediatr Nephrol 2023; 38:2851-2860. [PMID: 36790467 DOI: 10.1007/s00467-023-05886-1] [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: 09/01/2022] [Revised: 01/09/2023] [Accepted: 01/09/2023] [Indexed: 02/16/2023]
Abstract
BACKGROUND Children who require surgery for congenital heart disease have increased risk for long-term chronic kidney disease (CKD). Clinical factors as well as urine biomarkers of tubular health and injury may help improve the prognostication of estimated glomerular filtration rate (eGFR) decline. METHODS We enrolled children from 1 month to 18 years old undergoing cardiac surgery in the ASSESS-AKI cohort. We used mixed-effect models to assess the association between urinary biomarkers (log2-transformed uromodulin, NGAL, KIM-1, IL-18, L-FABP) measured 3 months after cardiac surgery and cyanotic heart disease with the rate of eGFR decline at annual in-person visits over 4 years. RESULTS Of the 117 children enrolled, 30 (24%) had cyanotic heart disease. During 48 months of follow-up, the median eGFR in the subgroup of children with cyanotic heart disease was lower at all study visits as compared with children with acyanotic heart disease (p = 0.01). In the overall cohort, lower levels of both urine uromodulin and IL-18 after discharge were associated with eGFR decline. After adjustment for age, RACHS-1 surgical complexity score, proteinuria, and eGFR at the 3-month study visit, lower concentrations of urine uromodulin and IL-18 were associated with a monthly decline in eGFR (uromodulin β = 0.04 (95% CI: 0.00-0.09; p = 0.07) IL-18 β = 0.07 (95% CI: 0.01-0.13; p = 0.04), ml/min/1.73 m2 per month). CONCLUSIONS At 3 months after cardiac surgery, children with lower urine uromodulin and IL-18 concentrations experienced a significantly faster decline in eGFR. Children with cyanotic heart disease had a lower median eGFR at all time points but did not experience faster eGFR decline. A higher-resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
| | - Michael Zappitelli
- Department of Pediatrics, Toronto Hospital for Sick Children, Toronto, Canada
| | | | - Yaqi Jia
- Department of Internal Medicine, Section of Nephrology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Paul L Kimmel
- National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, MD, USA
| | - James S Kaufman
- Division of Nephrology, New York University Grossman School of Medicine and VA New York Harbor Healthcare System, New York, NY, USA
| | - Prasad Devarajan
- Department of Nephrology and Hypertension, Cincinnati Children's Hospital, Cincinnati, OH, USA
| | - Chirag R Parikh
- Department of Internal Medicine, Section of Nephrology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Jason H Greenberg
- Clinical and Translational Research Accelerator, Yale University, New Haven, CT, USA.
- Department of Pediatrics, Section of Nephrology, Yale University, New Haven, CT, USA.
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28
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Che A, D’Arienzo D, Dart A, Mammen C, Samuel S, Alexander T, Morgan C, Blydt-Hansen T, Fontela P, Guerra GG, Chanchlani R, Wang S, Cockovski V, Jawa N, Lee J, Nunes S, Reynaud S, Zappitelli M. Perspectives of Pediatric Nephrologists, Intensivists and Nurses Regarding AKI Management and Expected Outcomes. Can J Kidney Health Dis 2023; 10:20543581231168088. [PMID: 37359983 PMCID: PMC10286545 DOI: 10.1177/20543581231168088] [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: 06/21/2022] [Accepted: 02/05/2023] [Indexed: 06/28/2023] Open
Abstract
Background Acute kidney injury (AKI) in critically ill children is associated with increased risk for short- and long-term adverse outcomes. Currently, there is no systematic follow-up for children who develop AKI in intensive care unit (ICU). Objective This study aimed to assess variation regarding management, perceived importance, and follow-up of AKI in the ICU setting within and between healthcare professional (HCP) groups. Design Anonymous, cross-sectional, web-based surveys were administered nationally to Canadian pediatric nephrologists, pediatric intensive care unit (PICU) physicians, and PICU nurses, via professional listservs. Setting All Canadian pediatric nephrologists, PICU physicians, and nurses treating children in the ICU were eligible for the survey. Patients N/A. Measurements Surveys included multiple choice and Likert scale questions on current practice related to AKI management and long-term follow-up, including institutional and personal practice approaches, and perceived importance of AKI severity with different outcomes. Methods Descriptive statistics were performed. Categorical responses were compared using Chi-square or Fisher's exact tests; Likert scale results were compared using Mann-Whitney and Kruskal-Wallis tests. Results Surveys were completed by 34/64 (53%) pediatric nephrologists, 46/113 (41%) PICU physicians, and 82 PICU nurses (response rate unknown). Over 65% of providers reported hemodialysis to be prescribed by nephrology; a mix of nephrology, ICU, or a shared nephrology-ICU model was reported responsible for peritoneal dialysis and continuous renal replacement therapy (CRRT). Severe hyperkalemia was the most important renal replacement therapy (RRT) indication for both nephrologists and PICU physicians (Likert scale from 0 [not important] to 10 [most important]; median = 10, 10, respectively). Nephrologists reported a lower threshold of AKI for increased mortality risk; 38% believed stage 2 AKI was the minimum compared to 17% of PICU physicians and 14% of nurses. Nephrologists were more likely than PICU physicians and nurses to recommend long-term follow-up for patients who develop any AKI during ICU stay (Likert scale from 0 [none] to 10 [all patients]; mean=6.0, 3.8, 3.7, respectively) (P < .05). Limitations Responses from all eligible HCPs in the country could not obtained. There may be differences in opinions between HCPs that completed the survey compared to those that did not. Additionally, the cross-sectional design of our study may not adequately reflect changes in guidelines and knowledge since survey completion, although no specific guidelines have been released in Canada since survey dissemination. Conclusions Canadian HCP groups have variable perspectives on pediatric AKI management and follow-up. Understanding practice patterns and perspectives will help optimize pediatric AKI follow-up guideline implementation.
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Affiliation(s)
- Adrian Che
- The Hospital for Sick Children, University of Toronto, ON, Canada
| | - David D’Arienzo
- Faculty of Medicine, McGill University, Montreal, QC, Canada
| | - Allison Dart
- Department of Pediatrics and Child Health, Max Rady College of Medicine, Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada
| | - Cherry Mammen
- Division of Nephrology, Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia, Vancouver, Canada
| | - Susan Samuel
- Department of Pediatrics, Section of Pediatric Nephrology, Alberta Children’s Hospital, University of Calgary, Canada
| | - Todd Alexander
- Department of Pediatrics, University of Alberta, Edmonton, Canada
| | - Catherine Morgan
- Department of Pediatrics, University of Alberta, Edmonton, Canada
| | - Tom Blydt-Hansen
- Pediatric Nephrology, BC Children’s Hospital, The University of British Columbia, Vancouver, Canada
| | - Patricia Fontela
- Department of Pediatrics, McGill University, Montreal, QC, Canada
| | - Gonzalo Garcia Guerra
- Intensive Care Unit, Department of Pediatrics, Stollery Children’s Hospital, University of Alberta, Edmonton, Canada
| | - Rahul Chanchlani
- Division of Nephrology, Department of Pediatrics, McMaster University, Hamilton, ON, Canada
| | - Stella Wang
- The Hospital for Sick Children, University of Toronto, ON, Canada
| | - Vedran Cockovski
- The Hospital for Sick Children, University of Toronto, ON, Canada
| | - Natasha Jawa
- The Hospital for Sick Children, University of Toronto, ON, Canada
| | - Jasmine Lee
- The Hospital for Sick Children, University of Toronto, ON, Canada
| | - Sophia Nunes
- The Hospital for Sick Children, University of Toronto, ON, Canada
| | | | - Michael Zappitelli
- Division of Pediatric Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada
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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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Dixon CG, Thadani S, Fitzgerald JC, Akcan-Arikan A, Yehya N. Fluid Overload Precedes and Masks Cryptic Kidney Injury in Pediatric Acute Respiratory Distress Syndrome. Crit Care Med 2023; 51:765-774. [PMID: 36939256 PMCID: PMC10214878 DOI: 10.1097/ccm.0000000000005836] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/21/2023]
Abstract
OBJECTIVES Given the complex interrelatedness of fluid overload (FO), creatinine, acute kidney injury (AKI), and clinical outcomes, the association of AKI with poor outcomes in critically ill children may be underestimated due to definitions used. We aimed to disentangle these temporal relationships in a large cohort of children with acute respiratory distress syndrome (ARDS). DESIGN Retrospective cohort study. SETTING Quaternary care PICU. PATIENTS Seven hundred twenty intubated children with ARDS between 2011 and 2019. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Daily fluid balance, urine output (UOP), and creatinine for days 1-7 of ARDS were retrospectively abstracted. A subset of patients had angiopoietin 2 (ANGPT2) quantified on days 1, 3, and 7. Patients were classified as AKI by Kidney Disease Improving Global Outcomes (KDIGO) stage 2/3 then grouped by timing of AKI onset (early if days 1-3 of ARDS, late if days 4-7 of ARDS, persistent if both) for comparison of PICU mortality and ventilator-free days (VFDs). A final category of "Cryptic AKI" was used to identify subjects who met KDIGO stage 2/3 criteria only when creatinine was adjusted for FO. Outcomes were compared between those who had Cryptic AKI identified by FO-adjusted creatinine versus those who had no AKI. Conventionally defined AKI occurred in 26% of patients (early 10%, late 3%, persistent 13%). AKI was associated with higher mortality and fewer VFDs, with no differences according to timing of onset. The Cryptic AKI group (6% of those labeled no AKI) had higher mortality and fewer VFDs than patients who did not meet AKI with FO-adjusted creatinine. FO, FO-adjusted creatinine, and ANGPT2 increased 1 day prior to meeting AKI criteria in the late AKI group. CONCLUSIONS AKI was associated with higher mortality and fewer VFDs in pediatric ARDS, irrespective of timing. FO-adjusted creatinine captures a group of patients with Cryptic AKI with outcomes approaching those who meet AKI by traditional criteria. Increases in FO, FO-adjusted creatinine, and ANGPT2 occur prior to meeting conventional AKI criteria.
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Affiliation(s)
- Celeste G. Dixon
- Division of Critical Care Medicine, Department of Pediatrics, Children's National Medical Center, Washington, District of Columbia
| | - Sameer Thadani
- Divisions of Critical Care Medicine and Nephrology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas
| | - Julie C. Fitzgerald
- Division of Pediatric Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Ayse Akcan-Arikan
- Divisions of Critical Care Medicine and Nephrology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas
| | - Nadir Yehya
- Division of Pediatric Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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31
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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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32
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Selewski DT, Gist KM, Basu RK, Goldstein SL, Zappitelli M, Soranno DE, Mammen C, Sutherland SM, Askenazi DJ, Ricci Z, Akcan-Arikan A, Gorga SM, Gillespie SE, Woroniecki R. Impact of the Magnitude and Timing of Fluid Overload on Outcomes in Critically Ill Children: A Report From the Multicenter International Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) Study. Crit Care Med 2023; 51:606-618. [PMID: 36821787 DOI: 10.1097/ccm.0000000000005791] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2023]
Abstract
OBJECTIVES With the recognition that fluid overload (FO) has a detrimental impact on critically ill children, the critical care nephrology community has focused on identifying clinically meaningful targets for intervention. The current study aims to evaluate the epidemiology and outcomes associated with FO in an international multicenter cohort of critically ill children. The current study also aims to evaluate the association of FO at predetermined clinically relevant thresholds and time points (FO ≥ 5% and FO ≥ 10% at the end of ICU days 1 and 2) with outcomes. DESIGN Prospective cohort study. SETTING Multicenter, international collaborative of 32 pediatric ICUs. PATIENTS A total of 5,079 children and young adults admitted consecutively to pediatric ICUs as part of the Assessment of the Worldwide Acute Kidney Injury, Renal Angina and Epidemiology Study. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The FO thresholds at the time points of interest occurred commonly in the cohort (FO ≥ 5%Day1 in 38.1% [ n = 1753], FO ≥ 10%Day1 in 11.7% [ n = 537], FO ≥ 5%Day2 in 53.3% [ n = 1,539], FO ≥ 10%Day2 in 25.1% [ n = 724]). On Day1, multivariable modeling demonstrated that FO ≥ 5% was associated with fewer ICU-free days, and FO ≥ 10% was associated with higher mortality and fewer ICU and ventilator-free days. On multivariable modeling, FO-peak, Day2 FO ≥ 5%, and Day2 FO ≥ 10% were associated with higher mortality and fewer ICU and ventilator-free days. CONCLUSIONS This study found that mild-to-moderate FO as early as at the end of ICU Day1 is associated with adverse outcomes. The current study fills an important void in the literature by identifying critical combinations of FO timing and quantity associated with adverse outcomes (FO ≥ 5%Day1, FO ≥10%Day1, FO ≥ 5%Day2, and FO ≥ 10%Day2). Those novel findings will help guide the development of interventional strategies and trials targeting the treatment and prevention of clinically relevant FO.
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Affiliation(s)
- David T Selewski
- Division of Nephrology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC
| | - Katja M Gist
- Division of Cardiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH
| | - Rajit K Basu
- Ann & Robert Lurie Children's Hospital of Chicago/Northwestern University School of Medicine, Chicago, IL
| | - Stuart L Goldstein
- Center for Acute Care Nephrology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Michael Zappitelli
- Division of Nephrology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Danielle E Soranno
- Section of Pediatric Nephrology, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN
| | - Cherry Mammen
- Department of Pediatrics, Division of Nephrology, BC Children's Hospital, Vancouver, BC, Canada
| | - Scott M Sutherland
- Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA
| | - David J Askenazi
- Department of Pediatrics, Division of Nephrology, Pediatric and Infant Center for Acute Nephrology (PICAN), University of Alabama at Birmingham, Birmingham, AL
| | - Zaccaria Ricci
- Department of Emergency and Intensive Care, Pediatric Intensive Care Unit, Azienda Ospedaliero Universitaria Meyer, Firenze, Italy
- Department of Health Science, University of Florence, Firenze, Italy
| | - Ayse Akcan-Arikan
- Division of Nephrology, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
- Division of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Stephen M Gorga
- Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI
| | - Scott E Gillespie
- Division of Critical Care Medicine, Department of Pediatrics, Emory University, Atlanta, GA
| | - Robert Woroniecki
- Division of Nephrology, Department of Pediatrics, Renaissance School of Medicine at Stonybrook Children's Hospital, Stony Brook, NY
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Schuermans A, Van den Eynde J, Mekahli D, Vlasselaers D. Long-term outcomes of acute kidney injury in children. Curr Opin Pediatr 2023; 35:259-267. [PMID: 36377251 DOI: 10.1097/mop.0000000000001202] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE OF REVIEW Acute kidney injury (AKI) affects up to 35% of all critically ill children and is associated with substantial short-term morbidity and mortality. However, the link between paediatric AKI and long-term adverse outcomes remains incompletely understood. This review highlights the most recent clinical data supporting the role of paediatric AKI as a risk factor for long-term kidney and cardiovascular consequences. In addition, it stresses the need for long-term surveillance of paediatric AKI survivors. RECENT FINDINGS Recent large-scale studies have led to an increasing understanding that paediatric AKI is a significant risk factor for adverse outcomes such as hypertension, cardiovascular disease and chronic kidney disease (CKD) over time. These long-term sequelae of paediatric AKI are most often observed in vulnerable populations, such as critically ill children, paediatric cardiac surgery patients, children who suffer from severe infections and paediatric cancer patients. SUMMARY A growing body of research has shown that paediatric AKI is associated with long-term adverse outcomes such as CKD, hypertension and cardiovascular disease. Although therapeutic pathways tailored to individual paediatric AKI patients are yet to be validated, we provide a framework to guide monitoring and prevention in children at the highest risk for developing long-term kidney dysfunction.
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Affiliation(s)
- Art Schuermans
- PKD Research Group, Department of Cellular and Molecular Medicine, KU Leuven
| | - Jef Van den Eynde
- PKD Research Group, Department of Cellular and Molecular Medicine, KU Leuven
| | - Djalila Mekahli
- PKD Research Group, Department of Cellular and Molecular Medicine, KU Leuven
- Department of Pediatric Nephrology, University Hospitals Leuven
| | - Dirk Vlasselaers
- Department of Intensive Care Medicine, University Hospitals Leuven
- Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
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Robinson CH, Klowak JA, Jeyakumar N, Luo B, Wald R, Garg AX, Nash DM, McArthur E, Greenberg JH, Askenazi D, Mammen C, Thabane L, Goldstein S, Silver SA, Parekh RS, Zappitelli M, Chanchlani R. Long-term Health Care Utilization and Associated Costs After Dialysis-Treated Acute Kidney Injury in Children. Am J Kidney Dis 2023; 81:79-89.e1. [PMID: 35985371 DOI: 10.1053/j.ajkd.2022.07.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 07/10/2022] [Indexed: 12/24/2022]
Abstract
RATIONALE & OBJECTIVE Acute kidney injury (AKI) is common among hospitalized children and is associated with increased hospital length of stay and costs. However, there are limited data on postdischarge health care utilization after AKI hospitalization. Our objectives were to evaluate health care utilization and physician follow-up patterns after dialysis-treated AKI in a pediatric population. STUDY DESIGN Retrospective cohort study, using provincial health administrative databases. SETTING & PARTICIPANTS All children (0-18 years) hospitalized between 1996 and 2017 in Ontario, Canada. Excluded individuals comprised non-Ontario residents; those with metabolic disorders or poisoning; and those who received dialysis or kidney transplant before admission, a kidney transplant by 104 days after discharge, or were receiving dialysis 76-104 days from dialysis start date. EXPOSURE Episodes of dialysis-treated AKI, identified using validated health administrative codes. AKI survivors were matched to 4 hospitalized controls without dialysis-treated AKI by age, sex, and admission year. OUTCOME Our primary outcome was postdischarge hospitalizations, emergency department visits, and outpatient physician visits. Secondary outcomes included outpatient visits by physician type and composite health care costs. ANALYTICAL APPROACH Proportions with≥1 event and rates (per 1,000 person-years). Total and median composite health care costs. Adjusted rate ratios using negative binomial regression models. RESULTS We included 1,688 pediatric dialysis-treated AKI survivors and 6,752 matched controls. Dialysis-treated AKI survivors had higher rehospitalization and emergency department visit rates during the analyzed follow-up periods (0-1, 0-5, and 0-10 years postdischarge, and throughout follow-up), and higher outpatient visit rates in the 0-1-year follow-up period. The overall adjusted rate ratio for rehospitalization was 1.46 (95% CI, 1.25-1.69; P<0.0001) and for outpatient visits was 1.16 (95% CI, 1.09-1.23; P=0.01). Dialysis-treated AKI survivors also had higher health care costs. Nephrologist follow-up was infrequent among dialysis-treated AKI survivors (18.6% by 1 year postdischarge). LIMITATIONS Potential miscoding of study exposures or outcomes. Residual uncontrolled confounding. Data for health care costs and emergency department visits was unavailable before 2006 and 2001, respectively. CONCLUSIONS Dialysis-treated AKI survivors had greater postdischarge health care utilization and costs versus hospitalized controls. Strategies are needed to improve follow-up care for children after dialysis-treated AKI to prevent long-term complications.
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Affiliation(s)
- Cal H Robinson
- Division of Paediatric Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, Ontario, Canada
| | | | | | | | - Ron Wald
- Division of Nephrology, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada
| | | | | | | | - Jason H Greenberg
- Division of Nephrology, Department of Pediatrics, Yale University, New Haven, Connecticut
| | - David Askenazi
- Division of Pediatric Nephrology, Department of Pediatrics, University of Alabama, Birmingham, Alabama
| | - Cherry Mammen
- Division of Nephrology, Department of Pediatrics, University of British Columbia, Vancouver, British Colombia, Canada
| | - Lehana Thabane
- Department of Pediatrics, Ontario, Canada; Department of Health Research Methods, Evidence and Impact, Ontario, Canada; Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada; Biostatistics Unit, St Joseph's Healthcare, Hamilton, Ontario, Canada
| | - Stuart Goldstein
- Center for Acute Care Nephrology, Cincinnati Children's Hospital, Ohio
| | - Samuel A Silver
- Division of Nephrology, Kingston Health Sciences Centre, Queen's University, Kingston, Ontario, Canada
| | - Rulan S Parekh
- Division of Paediatric Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Michael Zappitelli
- Division of Paediatric Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Rahul Chanchlani
- Division of Pediatric Nephrology, Ontario, Canada; Department of Health Research Methods, Evidence and Impact, Ontario, Canada; ICES, Ontario, Canada.
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Abbas Q, Laghari P, Jurair H, Nafis J, Saeed B, Qazi MF, Saleem A, Khan AHH, Haque A. Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Acute Kidney Injury in Children With Shock: A Prospective Study. Cureus 2023; 15:e34407. [PMID: 36874735 PMCID: PMC9977468 DOI: 10.7759/cureus.34407] [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] [Accepted: 01/29/2023] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND The current definition of acute kidney injury (AKI) is based on serum creatinine (SrCr) and urine output, limited by delayed identification of such patients. Plasma neutrophil gelatinase-associated lipocalin (NGAL) is considered an early diagnostic and highly predictive biomarker of AKI. OBJECTIVE To determine the diagnostic accuracy of NGAL for AKI compared with creatinine clearance for early detection of AKI in children with shock receiving inotropic support. METHODS Critically ill children requiring inotropic support in the pediatric intensive care unit were enrolled prospectively. SrCr and NGAL values were obtained three times at six, 12, and 48 hours after vasopressor initiation. Patients with AKI were defined as having loss of >25% renal function based on creatinine clearance within 48 hours. NGAL level of more than 150 ng/dl was suggestive of the diagnosis of AKI. Receiver operator characteristic curves were generated for NGAL and SrCr to compare the predictive ability of both at 0, 12, and 48 hours of starting vasopressor support. Results: A total of 94 patients were enrolled. The mean age was 43±50.95 months. Most common primary diagnoses were related to the cardiovascular system (46%). Twenty-nine patients (31%) died during the hospital stay. Thirty-four patients (36%) developed AKI within 48 hours following shock. The area under the curve (AUC) for NGAL at a cutoff of 150 ng/ml was 0.70, 0.74, and 0.73 at six-hour, 12-hour, and 48-hour follow-up, respectively. NGAL had a sensitivity of 85.3% and specificity of 50% at 0 hours of follow-up for diagnosis of AKI. CONCLUSION Serum NGAL has better sensitivity and AUC compared to SrCr for early diagnosis of AKI in children admitted with shock.
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Affiliation(s)
- Qalab Abbas
- Department of Pediatrics and Child Health, Aga Khan University Hospital, Karachi, PAK
| | - Parveen Laghari
- Department of Pediatrics and Child Health, Aga Khan University Hospital, Karachi, PAK
| | - Humaira Jurair
- Department of Pediatrics Pediatric Intensive Care Unit (PICU), The Indus Hospital, Karachi, PAK
| | - Javeria Nafis
- Department of Community Health Sciences, Aga Khan University Hospital, Karachi, PAK
| | - Bushra Saeed
- Department of Pediatrics and Child Health, Aga Khan University Hospital, Karashi, PAK
| | - Muhammad F Qazi
- Department of Pediatrics and Child Health, Aga Khan University Hospital, Karachi, PAK
| | - Ali Saleem
- Pediatrics, Aga Khan University Hospital, Karachi, PAK
| | - Aysha Habib H Khan
- Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, PAK
| | - Anwar Haque
- Pediatrics, The Indus Hospital, Karachi, PAK
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Van den Eynde J, Rotbi H, Schuermans A, Hassanabad AF, Gewillig M, Budts W, Kutty S, Mekahli D. Long-Term Consequences of Acute Kidney Injury After Pediatric Cardiac Surgery: A Systematic Review. J Pediatr 2023; 252:83-92.e5. [PMID: 36096176 DOI: 10.1016/j.jpeds.2022.09.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 09/01/2022] [Accepted: 09/06/2022] [Indexed: 12/29/2022]
Abstract
OBJECTIVE The objective of this study was to evaluate the available data on long-term kidney dysfunction, hypertension, and mortality after cardiac surgery-associated acute kidney injury (AKI) in the pediatric population. STUDY DESIGN PubMed/MEDLINE, Embase, Scopus, and reference lists of relevant articles were searched for eligible studies published from inception through March 2022. Long-term outcomes after pediatric cardiac surgery complicated by AKI and those without were investigated. RESULTS We identified 14 studies published between 2013 and 2022 that included a total of 6701 patients (AKI: 1376 patients; no AKI: 5325 patients). These studies used different well-established classifications to define AKI. All the studies suggested that AKI after heart surgery is common in the pediatric patient population and reported a potential link between cardiac surgery-associated AKI and important clinical outcomes. However, only 4 out of 11 studies found a strong association between (absence of recovery from) cardiac surgery-associated AKI and risk of developing chronic kidney disease, and 3 out of 5 studies found a significant increase in mortality rates for pediatric patients who developed AKI after cardiac surgery. Only 1 out of 4 studies found an association between AKI and hypertension at 12 months postoperatively, but found no association at later follow-up times. CONCLUSIONS Although there is a trend, evidence on the long-term consequences of cardiac surgery-associated AKI in the pediatric population is mixed. Genetic syndromes, preexisting kidney disease, univentricular or cyanotic heart conditions, and/or high-complexity surgery may be more important for the development of kidney dysfunction by adolescence and early adulthood. Regardless, these children may benefit from a long-term kidney follow-up.
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Affiliation(s)
- Jef Van den Eynde
- Helen B. Taussig Heart Center, The Johns Hopkins Hospital and School of Medicine, Baltimore, MA; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
| | - Hajar Rotbi
- Faculty of Medicine, Radboud University, Nijmegen, The Netherlands; Radboud Institute for Health Sciences, Department of Physiology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Art Schuermans
- Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
| | - Ali Fatehi Hassanabad
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, Calgary, Alberta, Canada
| | - Marc Gewillig
- Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; Pediatric Cardiology, University Hospitals Leuven, Leuven, Belgium
| | - Werner Budts
- Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; Congenital and Structural Cardiology, UZ Leuven, Leuven, Belgium
| | - Shelby Kutty
- Helen B. Taussig Heart Center, The Johns Hopkins Hospital and School of Medicine, Baltimore, MA
| | - Djalila Mekahli
- Department of Pediatric Nephrology, University Hospitals of Leuven, Leuven, Belgium; PKD Research Group, GPURE, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
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Leow EH, Lee JH, Hornik CP, Ng YH, Hays T, Clark RH, Tolia VN, Greenberg RG. Congenital anomalies of the kidney and urinary tract (CAKUT) in critically ill infants: a multicenter cohort study. Pediatr Nephrol 2023; 38:161-172. [PMID: 35467155 DOI: 10.1007/s00467-022-05542-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 03/02/2022] [Accepted: 03/11/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND The aim of the study was to determine the prevalence of congenital anomalies of the kidney and urinary tract (CAKUT) in the neonatal intensive care unit (NICU) and to evaluate risk factors associated with worse outcomes. We hypothesized that infants with CAKUT with extra-renal manifestations have higher mortality. METHODS This is a cohort study of all inborn infants who were diagnosed with any form of CAKUT discharged from NICUs managed by the Pediatrix Medical Group from 1997 to 2018. Logistic and linear regression models were used to analyze risk factors associated with in-hospital mortality. RESULTS The prevalence of CAKUT was 1.5% among infants hospitalized in 419 NICUs. Among the 13,383 infants with CAKUT analyzed, median gestational age was 35 (interquartile range [IQR] 31-38) weeks and median birth weight was 2.34 (IQR 1.54-3.08) kg. Overall in-hospital mortality for infants with CAKUT was 6.8%. Oligohydramnios (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] 2.2-9.1, p < 0.001), extra-renal anomalies (aOR 2.5, 95% CI 2.0-3.1, p < 0.001), peak SCr (aOR 1.02, 95% CI 1.01-1.03, p < 0.001) and exposure to nephrotoxic medications (aOR 1.4, 95% CI 1.1-1.7, p = 0.01) were associated with increased mortality, while a history of urological surgery or intervention was associated with lower mortality (aOR 0.6, 95% CI 0.4-0.7, p < 0.001). CONCLUSIONS Infants hospitalized in the NICU who have CAKUT and the independent risk factors for mortality (e.g., oligohydramnios and presence of extra-renal anomalies) require close monitoring, minimizing of exposure to nephrotoxic drugs, and timely urological surgery or intervention. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Esther Huimin Leow
- Paediatric Nephrology, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore.
| | - Jan Hau Lee
- Children's Intensive Care Unit, KK Women's and Children's Hospital, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Christoph P Hornik
- Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA
- Duke Clinical Research Institute, Durham, NC, USA
| | - Yong Hong Ng
- Paediatric Nephrology, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore
| | - Thomas Hays
- Division of Neonatology, Department of Pediatrics, Columbia University Irving Medical Center, New York City, NY, USA
| | - Reese H Clark
- Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA
- The MEDNAX Center for Research, Education, Quality and Safety, Sunrise, FL, USA
| | - Veeral N Tolia
- The MEDNAX Center for Research, Education, Quality and Safety, Sunrise, FL, USA
- Department of Neonatology, Baylor University Medical Center and Pediatrix Medical Group, Dallas, TX, USA
| | - Rachel G Greenberg
- Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA
- Duke Clinical Research Institute, Durham, NC, USA
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Magunia H, Nester J, Sandoval Boburg R, Schlensak C, Rosenberger P, Hofbeck M, Keller M, Neunhoeffer F. Abdominal and Peripheral Tissue Oxygen Supply during Selective Lower Body Perfusion for the Surgical Repair of Congenital Heart Disease: A Pilot Study. J Cardiovasc Dev Dis 2022; 9:jcdd9120436. [PMID: 36547433 PMCID: PMC9782002 DOI: 10.3390/jcdd9120436] [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: 11/10/2022] [Revised: 11/22/2022] [Accepted: 12/02/2022] [Indexed: 12/11/2022] Open
Abstract
Background: Lower body perfusion (LBP) may be a strategy for maintaining organ perfusion during congenital heart disease surgery. It is hypothesized that renal and lower limb oxygen supply during LBP is superior to off-pump surgery and comparable to that of a standard cardiopulmonary bypass (CPB). Methods: in this prospective single-center study, patients aged <1 year were recruited if they were scheduled for a correction of aortic arch anomalies using antegrade cerebral perfusion and LBP (group 1), a repair of coarctation during aortic cross-clamping (group 2), or surgery under whole-body CPB (group 3). Renal (prefix “r”) and peripheral (prefix “p”) oxygen saturation (SO2), hemoglobin amount (Hb), blood velocity (Velo), and blood flow (Flow) were measured noninvasively. Results: A total of 23 patients were included (group 1, n = 9; group 2, n = 5; group 3, n = 9). Compared to the baseline values, rSO2 and pSO2 decreased significantly in group 2 compared to groups 1 and 3. Conversely, rHB significantly increased in group 2 compared to groups 1 and 3, reflecting abdominal venous stasis. Compared to group 3, group 1 showed a significantly lower pFlow during CPB; however, rFlow, pFlow, and pVelo did not differ. Conclusion: according to these observations, LBP results in an improved renal oxygen supply compared to off-pump surgery and may prove to be a promising alternative to conventional CPB.
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Affiliation(s)
- Harry Magunia
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany
| | - Jana Nester
- Department of Cardiovascular and Thoracic Surgery, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany
| | - Rodrigo Sandoval Boburg
- Department of Cardiovascular and Thoracic Surgery, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany
| | - Christian Schlensak
- Department of Cardiovascular and Thoracic Surgery, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany
| | - Peter Rosenberger
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany
| | - Michael Hofbeck
- Department of Pediatric Cardiology, Pulmonology and Intensive Care Medicine, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 1, 72076 Tuebingen, Germany
| | - Marius Keller
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany
- Correspondence: ; Tel.: +49-(0)7071-2986564; Fax: +49-(0)7071-295533
| | - Felix Neunhoeffer
- Department of Pediatric Cardiology, Pulmonology and Intensive Care Medicine, University Hospital Tuebingen, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 1, 72076 Tuebingen, Germany
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Radel LJ, Branstetter J, Jones TL, Briceno-Medina M, Tadphale SD, Onder AM, Rayburn MS. Use of Aminophylline to Reverse Acute Kidney Injury in Pediatric Critical Care Patients. J Pediatr Pharmacol Ther 2022; 27:739-745. [DOI: 10.5863/1551-6776-27.8.739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 03/01/2022] [Indexed: 11/18/2022]
Abstract
OBJECTIVE
Acute kidney injury (AKI) is a complication encountered in 18% to 51% of pediatric critical care patients admitted for treatment of other primary diagnoses and is an independent risk factor for increased morbidity and mortality. Aminophylline has shown promise as a medication to treat AKI, but published studies have shown conflicting results. Our study seeks to assess the reversal of AKI following the administration of aminophylline in critically ill pediatric patients.
METHODS
We performed a single-institution retrospective chart review of pediatric inpatients who were diagnosed with AKI and subsequently treated with non-continuous dose aminophylline between January 2016 and December 2018. Data were collected beginning 2 days prior to the initial dose of aminophylline through completion of the 5-day aminophylline course.
RESULTS
Nineteen therapies among 17 patients were included in analysis. Twelve of the therapies resulted in resolution of AKI during the study period. We observed urine output increase of 19% (p = 0.0063) on the day following initiation of aminophylline therapy in the subset of patients whose AKI resolved. Trends toward decreased serum creatinine and lower inotropic support were also noted.
CONCLUSIONS
Based on these findings, aminophylline could be considered a potentially effective medication for use as rescue therapy in critically ill children with AKI. Limitations include small study population and retrospective nature. Further research in this area with a larger study population and a randomized control trial would allow for better characterization of the efficacy of aminophylline in reversal of AKI.
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Affiliation(s)
- Laura J. Radel
- Department of Pediatric Cardiology (LJR, MBM, SDT), Le Bonheur Children's Hospital and University of Tennessee Health Science Center, Memphis, TN
| | - Joshua Branstetter
- Department of Pharmacy (MSR), Le Bonheur Children's Hospital and University of Tennessee Health Science Center, Memphis, TN
| | - Tamekia L. Jones
- Department of Pediatrics and Preventive Medicine (TLJ), University of Tennessee Health Science Center and Children's Foundation Research Institute, Memphis, TN
| | - Mario Briceno-Medina
- Department of Pediatric Cardiology (LJR, MBM, SDT), Le Bonheur Children's Hospital and University of Tennessee Health Science Center, Memphis, TN
| | - Sachin D. Tadphale
- Department of Pediatric Cardiology (LJR, MBM, SDT), Le Bonheur Children's Hospital and University of Tennessee Health Science Center, Memphis, TN
| | - Ali Mirza Onder
- Department of Nephrology (AMO), Children's of Mississippi and University of Mississippi Medical Campus, Jackson, MS
| | - Mark S. Rayburn
- Department of Pharmacy (MSR), Le Bonheur Children's Hospital and University of Tennessee Health Science Center, Memphis, TN
- Department of Clinical Pharmacy and Translational Science (MSR), University of Tennessee Health Science Center and Children's Foundation Research Institute, Memphis, TN
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Abstract
Acute kidney injury (AKI) is common in children and is associated with significant morbidity and mortality. In the last decade our understanding of AKI has improved significantly, and it is now considered a systemic disorder that affects other organs including heart, lung, and brain. In spite of its limitations, serum creatinine remains the mainstay in the diagnosis of AKI. However, newer approaches such as urinary biomarkers, furosemide stress test, and clinical decision support are being increasingly used and have the potential to improve the accuracy and timeliness of AKI diagnosis.
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Affiliation(s)
- Priyanka Khandelwal
- Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, Academic Block, Ansari Nagar, New Delhi 110029, India
| | - Nadia McLean
- Cornwall Regional Hospital, c/o Cornwall Regional Hospital, PO Box 900, Mount Salem, Montego Bay #2 PO, St. James, Jamaica, West Indies
| | - Shina Menon
- Department of Pediatrics, Division of Nephrology, University of Washington, Seattle Children's Hospital, 4800 Sand Point Way NE, Mailstop OC9.820, Seattle, WA 98103, USA.
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Mbanefo NR, Uwaezuoke SN, Chikani UN, Bisi-Onyemaechi AI, Muoneke UV, Odetunde OI, Okafor HU. The effectiveness of locally-prepared peritoneal dialysate in the management of children with acute kidney injury in a south-east Nigerian tertiary hospital. Afr Health Sci 2022; 22:679-685. [PMID: 37092055 PMCID: PMC10117520 DOI: 10.4314/ahs.v22i4.74] [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] [Indexed: 03/06/2023] Open
Abstract
BACKGROUND Peritoneal dialysis (PD) is the preferred mode of renal replacement therapy (RRT) in children with acute kidney injury (AKI). The gold standard remains the use of commercially-prepared PD fluid. In resource-poor nations, its availability and affordability remain a challenge. AIM This study aims to report the effectiveness of locally-prepared PD fluid in the management of AKI in a south-east Nigerian tertiary hospital. SUBJECTS AND METHODS This was a retrospective study conducted at the paediatric ward of the University of Nigeria Teaching hospital, Enugu. The case records of 36 children seen over three years, diagnosed with AKI and requiring PD were reviewed. The retrieved information comprised biodata, aetiology of AKI, indications for PD, pre-and post-dialysis estimated glomerular filtration rate (eGFR) and patient outcomes. RESULTS The children (20 males and 16 females) were aged 3 to 36 months with a mean age of 9.92 ± 6.29 months. The common aetiologies of AKI were septicemia (30.6%), hemolytic uremic syndrome (19.4%), and toxic nephropathy (16.7%). The frequent indications for PD were uremic encephalopathy (58.3%) and severe metabolic acidosis (38.8%). The pre-and post-dialysis mean urine flow rate was 0.16 + 0.13 and 2.77 + 0.56 ml/kg/hour respectively. The eGFR before PD, at discontinuation, and a week later was 6.06 + 2.87, 24.44 + 15.71 and 59.07 + 22.22 mls/min/1.73m2 respectively. CONCLUSION PD with locally-prepared dialysate is safe, effective and a life-saving alternative in the management of AKI in children.
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Affiliation(s)
- Ngozi R Mbanefo
- Department of Paediatrics, University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu, Nigeria
| | - Samuel N Uwaezuoke
- Department of Paediatrics, University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu, Nigeria
| | - Ugo N Chikani
- Department of Paediatrics, University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu, Nigeria
| | - Ada I Bisi-Onyemaechi
- Department of Paediatrics, University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu, Nigeria
| | - Uzoamaka V Muoneke
- Department of Paediatrics, University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu, Nigeria
| | - Odutola I Odetunde
- Department of Paediatrics, University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu, Nigeria
| | - Henrietta U Okafor
- Department of Paediatrics, University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu, Nigeria
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Derivation and evaluation of baseline creatinine equations for hospitalized children and adolescents: the AKI baseline creatinine equation. Pediatr Nephrol 2022; 37:3223-3233. [PMID: 35507142 DOI: 10.1007/s00467-022-05571-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 03/23/2022] [Accepted: 03/25/2022] [Indexed: 01/10/2023]
Abstract
BACKGROUND Acute kidney injury (AKI) definitions incorporate baseline creatinine (Crb) values, but Crb are frequently unknown in pediatrics. Our primary aim was to derive and validate a novel AKI Baseline Creatinine (ABC) estimation equation and compare it to existing methods of estimating Crb values. METHODS We conducted a single-center retrospective analysis of pediatric patients (0-25 years) admitted from 2012 to 2019. Included patients required at least one outpatient Crb prior to hospitalization (gold standard). Novel equations were developed with demographic and initial creatinine data. Existing methods included back-calculating Crb based on Schwartz, Full Age Spectrum (FAS), and CKiD-under-25 (U25) equations. To determine an optimal equation, we compared novel and existing equations to the gold standard. RESULTS The optimal simplified equation (ABC) included only age and had R2 = 59.9% and 73.2% of values within 30% of true Crb. The precision increased significantly when the equation included age and minimum creatinine within initial 72 h (ABC-cr): R2 = 75.4% and 86.5% of values within 30% of true Crb. The best performing existing equation was the age-based FAS, which had R2 = 61.0% and 78.0% of values within 30% of true Crb. All other existing equations performed worse, some methods as low as 52.6% within 30% of true Crb. CONCLUSIONS The newly derived ABC equation is simple, and the ABC-cr equation can more accurately estimate Crb by ≥ 25% compared to previous methods. The potential applicability of these equations is vast, including faster recognition of AKI on initial patient contact and improved standardization of pediatric AKI definitions, enhancing health services research. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Garg PM, Paschal JL, Zhang M, Pippins M, Taylor C, Sanderson K, Reddy K, Askenazi D, Padbury JF, Hillegass WB. Clinical impact of severe acute kidney injury on post-operative and brain injury outcomes in preterm infants following surgical necrotizing enterocolitis. J Matern Fetal Neonatal Med 2022; 35:10124-10136. [PMID: 36093832 PMCID: PMC10986639 DOI: 10.1080/14767058.2022.2121917] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 06/24/2022] [Indexed: 10/14/2022]
Abstract
BACKGROUND To evaluate post-operative outcomes and white matter injury (WMI) using brain MRI at term equivalent in neonates with and without severe acute kidney injury (AKI) following surgical necrotizing enterocolitis (NEC). METHODS A retrospective cohort study comparing neonates with severe (Stage 2/3) vs. other (no AKI/Stage 1) AKI using KDIGO classification with multivariable models assessing this association in the context of multiple systemic comorbidities. RESULTS Of 103 neonates with surgical NEC, 60 (58%) had severe AKI. Those with severe AKI had lower birth weight (BW; 715 vs. 950 g; p = .023), more frequently treated with indomethacin (18.3 vs. 2.4%); p = .014), higher CRP levels at 24 h after NEC onset (14.4 [6.4-19.8] vs. 4.8 [1.6-13.4]; p = .005), higher presence of cholestasis (73.3 vs. 51.2%); p = .023), later age of NEC onset (14 vs. 7 d); p = .004), longer length of bowel resected (14.9 vs. 4.3 cm); p = .011), longer post-operative ileus days (14 vs. 9 d); p < .001), longer post-operative days at starting enteral feedings (15 vs. 10 d; p < .001), longer days of attainment of full enteral feedings (75 vs. 44.5 d; p = .008) and longer length of stay (140.5 vs. 94 d; p = .028) compared to those without severe AKI. Compared to infants without AKI by serum creatinine, those with AKI had significantly more cases of white matter abnormality (WMA; 90 vs. 36.6%; p < .001) and retinopathy of prematurity (63.9 vs. 35.3%; p = .017). In addition, the presence of AKI Stage 2 and 3 by serum creatinine was independently associated with higher odds of sustaining severe WMI level on an ordinal scale (OR = 6.2; 95% CI = (1.1-35.5); p = .041). CONCLUSIONS Neonates with severe AKI following surgical NEC were more likely to experience longer post-operative morbidity and higher WMI by MRI at term.
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Affiliation(s)
- Parvesh Mohan Garg
- Department of Pediatrics/Neonatology, University of Mississippi Medical Center, Jackson, MS, USA
| | - Jaslyn L Paschal
- Department of Pediatrics/Neonatology, University of Mississippi Medical Center, Jackson, MS, USA
| | - Mengna Zhang
- Department of Data Sciences, University of Mississippi Medical Center, Jackson, MS, USA
| | - Melissa Pippins
- Department of Pediatrics/Neonatology, University of Mississippi Medical Center, Jackson, MS, USA
| | - Charlotte Taylor
- Department of Radiology, University of Mississippi Medical Center, Jackson, MS, USA
| | - Keia Sanderson
- Department of Medicine, UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Kartik Reddy
- Department of Radiology, University of Mississippi Medical Center, Jackson, MS, USA
| | - David Askenazi
- Department of Pediatrics/Nephrology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - James F Padbury
- Department of Pediatrics, Davis School of Medicine, University of California, Sacramento, CA, USA
| | - William B Hillegass
- Department of Data Sciences, University of Mississippi Medical Center, Jackson, MS, USA
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
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Singh T, Mahajan V, Kaur J, D'Cruz S, Randev S, Guglani V, Singla S. Early diagnosis of kidney injury in a paediatric population: a prospective cohort study (E-DRIP STUDY). Pediatr Nephrol 2022; 37:2771-2779. [PMID: 35262799 DOI: 10.1007/s00467-022-05442-3] [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: 09/06/2021] [Revised: 12/07/2021] [Accepted: 12/22/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND Renal Angina Index (RAI) is a bedside tool for risk stratification of patients to predict acute kidney injury (AKI). Kidney biomarkers are better indicators of real-time injury and give us lead time for diagnosing impending AKI. METHODS We enrolled consecutive children aged 2 months-14 years admitted to a tertiary hospital in northern India over 2 years. RAI was calculated on day 0 (D0) and urinary (u) and plasma (p) neutrophil gelatinase-associated lipocalin (NGAL) were measured within 6 h of admission. Children were followed for the development of severe AKI on day 3 (D3) using Kidney Disease Improving Global Outcomes criteria to define and stage AKI. RESULTS Of the 253 children enrolled and analysed, 44 (17.4%) developed D3-AKI (stage 1 in 52.2%, stage 2 in 20.5% and stage 3 in 27.3%). Renal angina (RAI ≥ 8) on D0 was present in 66.7% children who developed stage 2/3 D3-AKI vs. 43.5% in children who did not develop D3-AKI /stage 1 AKI (p = 0.065). Area under ROC (AUROC) curve for D0-RAI to predict D3-severe-AKI was 0.66 (95% CI, 0.55-0.77). AUROC curve for uNGAL and pNGAL to predict D3-severe-AKI was 0.62 (95% CI, 0.50-0.74) and 0.48 (95% CI, 0.35-0.61), respectively. The severe AKI group had greater requirement of ventilation and inotropic support with mortality being thrice higher compared to the non-AKI group. CONCLUSION RAI ≥ 8 and uNGAL had a high negative predictive value but low sensitivity for predicting D3-severe-AKI. pNGAL had a poor predictive value for D3-severe-AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Tanvi Singh
- Department of Pediatrics, Government Medical College and Hospital, Sector 32, Chandigarh, 160030, India
| | - Vidushi Mahajan
- Department of Pediatrics, Government Medical College and Hospital, Sector 32, Chandigarh, 160030, India.
| | - Jasbinder Kaur
- Department of Biochemistry, Government Medical College and Hospital, Sector 32, Chandigarh, India
| | - Sanjay D'Cruz
- Department of General Medicine (Nephrology), Government Medical College and Hospital, Sector 32, Chandigarh, India
| | - Shivani Randev
- Department of Pediatrics, Government Medical College and Hospital, Sector 32, Chandigarh, 160030, India
| | - Vishal Guglani
- Department of Pediatrics, Government Medical College and Hospital, Sector 32, Chandigarh, 160030, India
| | - Seema Singla
- Department of Biochemistry, Government Medical College and Hospital, Sector 32, Chandigarh, India
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Patel M, Gbadegesin RA. Update on prognosis driven classification of pediatric AKI. Front Pediatr 2022; 10:1039024. [PMID: 36340722 PMCID: PMC9634036 DOI: 10.3389/fped.2022.1039024] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 10/03/2022] [Indexed: 11/29/2022] Open
Abstract
Acute kidney injury (AKI) affects a large proportion of hospitalized children and increases morbidity and mortality in this population. Initially thought to be a self-limiting condition with uniformly good prognosis, we now know that AKI can persist and progress to acute kidney disease (AKD) and chronic kidney disease (CKD). AKI is presently categorized by stage of injury defined by increase in creatinine, decrease in eGFR, or decrease in urine output. These commonly used biomarkers of acute kidney injury do not change until the injury is well established and are unable to detect early stage of the disease when intervention is likely to reverse injury. The kidneys have the ability to compensate and return serum creatinine to a normal or baseline level despite nephron loss in the setting of AKI possibly masking persistent dysfunction. Though these definitions are important, classifying children by their propensity for progression to AKD and CKD and defining these risk strata by other factors besides creatinine may allow for better prognosis driven discussion, expectation setting, and care for our patients. In order to develop a classification strategy, we must first be able to recognize children who are at risk for AKD and CKD based on modifiable and non-modifiable factors as well as early biomarkers that identify their risk of persistent injury. Prevention of initial injury, prompt evaluation and treatment if injury occurs, and mitigating further injury during the recovery period may be important factors in decreasing risk of AKD and CKD after AKI. This review will cover presently used definitions of AKI, AKD, and CKD, recent findings in epidemiology and risk factors for AKI to AKD to CKD progression, novel biomarkers for early identification of AKI and AKI that may progress to CKD and future directions for improving outcome in children with AKI.
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Affiliation(s)
- Mital Patel
- Department of Pediatrics, Division of Pediatric Nephrology, Duke University, Durham, NC, United State
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Chronic implications of an acute disease: Long-term outcomes in pediatric Acute Kidney Injury Survivors. J Pediatr 2022; 255:7-8. [PMID: 36252862 DOI: 10.1016/j.jpeds.2022.10.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 10/09/2022] [Indexed: 11/27/2022]
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Acute kidney injury and diabetic kidney disease in children with acute complications of diabetes. Pediatr Nephrol 2022; 38:1643-1652. [PMID: 36227434 PMCID: PMC10060302 DOI: 10.1007/s00467-022-05735-7] [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: 04/10/2022] [Revised: 08/12/2022] [Accepted: 09/02/2022] [Indexed: 10/17/2022]
Abstract
BACKGROUND Diabetic ketoacidosis (DKA) and hyperglycaemia without ketoacidosis are common acute complications of diabetes. Their association with acute kidney injury (AKI) and diabetic kidney disease (DKD) was studied. METHODS The study group consisted of 197 children with type 1 diabetes with average diabetes duration of 8.08 ± 2.32 years. The medical history of the patients was retrospectively reviewed. The number of children with severe hyperglycaemia, DKA and AKI was assessed. The association with the risk of chronic kidney disease (CKD) was analysed. RESULTS AKI was found in 14% of cases hospitalised for DKA and 8% of cases hospitalised for hyperglycaemia. Patients with AKI showed a significantly increased corrected sodium (141.23 ± 5.09 mmol/L, p = 0.035). Patients with AKI in DKA showed a significant increase in WBC (20.73 ± 8.71 × 103/µL, p = 0.0009). Follow-up analysis after a minimum of 5 years of diabetes revealed that a single episode of DKA was found in 63 patients and a single episode of AKI in 18 patients. Two or more episodes of DKA were found in 18 patients, and nine cases were complicated by AKI. These patients showed a significant increase in urinary albumin excretion (44.20 ± 64.21 mg/24 h), the highest values of eGFR and the worst glycaemic control. CONCLUSIONS Diabetic children can develop AKI in the course of DKA and hyperglycaemia without ketoacidosis, which is associated with volume depletion and reflected by corrected sodium concentration. AKI in DKA seems to be complicated by stress and inflammation activation. AKI and poor glycaemic control with repeated DKA episodes can magnify the risk of progression to DKD. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Stenson EK, Kendrick J, Dixon B, Thurman JM. The complement system in pediatric acute kidney injury. Pediatr Nephrol 2022; 38:1411-1425. [PMID: 36203104 PMCID: PMC9540254 DOI: 10.1007/s00467-022-05755-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 08/08/2022] [Accepted: 09/09/2022] [Indexed: 10/24/2022]
Abstract
The complement cascade is an important part of the innate immune system. In addition to helping the body to eliminate pathogens, however, complement activation also contributes to the pathogenesis of a wide range of kidney diseases. Recent work has revealed that uncontrolled complement activation is the key driver of several rare kidney diseases in children, including atypical hemolytic uremic syndrome and C3 glomerulopathy. In addition, a growing body of literature has implicated complement in the pathogenesis of more common kidney diseases, including acute kidney injury (AKI). Complement-targeted therapeutics are in use for a variety of diseases, and an increasing number of therapeutic agents are under development. With the implication of complement in the pathogenesis of AKI, complement-targeted therapeutics could be trialed to prevent or treat this condition. In this review, we discuss the evidence that the complement system is activated in pediatric patients with AKI, and we review the role of complement proteins as biomarkers and therapeutic targets in patients with AKI.
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Affiliation(s)
- Erin K. Stenson
- grid.430503.10000 0001 0703 675XSection of Pediatric Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine, 13121 E 17th Avenue, MS8414, Aurora, CO 80045 USA
| | - Jessica Kendrick
- grid.430503.10000 0001 0703 675XDivision of Renal Disease and Hypertension, Department of Medicine, University of Colorado School of Medicine, Aurora, CO USA
| | - Bradley Dixon
- grid.430503.10000 0001 0703 675XRenal Section, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO USA
| | - Joshua M. Thurman
- grid.430503.10000 0001 0703 675XDivision of Renal Disease and Hypertension, Department of Medicine, University of Colorado School of Medicine, Aurora, CO USA
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Hessey E, Paun A, Benisty K, McMahon K, Palijan A, Pizzi M, Morgan C, Zappitelli M. 24-Hour ambulatory blood pressure monitoring 7 years after intensive care unit admission. Pediatr Nephrol 2022; 37:1877-1887. [PMID: 35039930 DOI: 10.1007/s00467-021-05392-2] [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: 07/26/2021] [Revised: 11/17/2021] [Accepted: 11/17/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Children who develop acute kidney injury (AKI) in the pediatric intensive care unit (PICU) may be at higher risk of long-term chronic kidney disease and hypertension. The objectives of this study were to determine the prevalence of post-discharge hypertension and albuminuria using reference-standard measurements in children admitted to the PICU, and evaluate their association with AKI. METHODS Single-center longitudinal cohort study of children admitted to the PICU from 2005 to 2010 with 7-8 years of follow-up (n = 207). Patients were excluded if they had pre-existing chronic kidney disease, were deceased, lived > 3.5-h drive away, were unwilling/unable to provide consent/assent, or had a clotting disorder. AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine definition. Office blood pressure was evaluated using age, sex, and height-based percentiles. Hypertension was defined using 24-h ambulatory blood pressure monitoring (ABPM). Albuminuria was defined as first morning urine albumin:creatinine ratio ≥ 30 mg/g. Prevalence of blood pressure outcomes was calculated. The association between AKI and outcomes was evaluated using multivariable regression. RESULTS Sixty of 207 (29%) children developed AKI during PICU admission. Overall, 6% had albuminuria and 21% had elevated office blood pressure or worse. One-hundred-and-seventy-seven (86%) patients had successful ABPM data. Of these, 10 (6%) had white coat, 18 (10%) had masked, and 5 (3%) had ambulatory hypertension. There was no statistically significant difference in outcomes across AKI stages. CONCLUSIONS Blood pressure abnormalities are common in children 7 years after PICU admission. Future studies with longer follow-up are needed to further evaluate the association between AKI and hypertension. A higher-resolution version of the graphical abstract is available as Supplementary information.
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Affiliation(s)
- Erin Hessey
- Department of Pediatrics, Division of Nephrology, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada
- Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada
| | - Alex Paun
- McGill University Health Centre Research Institute, McGill University Health Centre, Montreal, QC, Canada
| | - Kelly Benisty
- Department of Family Medicine, McGill University, Montreal, QC, Canada
| | - Kelly McMahon
- Department of Pediatrics, Division of Nephrology, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada
| | - Ana Palijan
- Department of Pediatrics, Division of Nephrology, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada
| | - Michael Pizzi
- Department of Pediatrics, Division of Nephrology, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada
| | - Catherine Morgan
- Department of Pediatrics, Division of Nephrology, Stollery Children's Hospital, University of Alberta, Edmonton, AB, Canada
| | - Michael Zappitelli
- Department of Pediatrics, Division of Nephrology, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, 686 Bay Street, 6th floor, Room 06.9708, Toronto, ON, M5G 0A4, Canada.
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Sethi SK, Raina R, Rana A, Agrawal G, Tibrewal A, Bajaj N, Gupta NP, Mirgunde S, Sahoo J, Balachandran B, Afzal K, Shrivastava A, Bagla J, Krishnegowda S, Konapur A, Soni K, Sharma D, Khooblall A, Khooblall P, Bunchman T, Wazir S. Validation of the STARZ neonatal acute kidney injury risk stratification score. Pediatr Nephrol 2022; 37:1923-1932. [PMID: 35020061 DOI: 10.1007/s00467-021-05369-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 10/25/2021] [Accepted: 10/25/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Neonatal acute kidney injury (AKI) is common in neonatal intensive care units (NICU) and leads to worse outcomes. Stratifying neonates into an "at risk" category allows health care providers to objectively recognize opportunities for improvements in quality of care. METHODS The "Neonatal AKI Risk Prediction Scoring" was devised as the "STARZ [Sethi, Tibrewal, Agrawal, Raina, waZir]" Score. The STARZ score was derived from our prior multicentre study analysing risk factors for AKI in neonates admitted to the NICU. This tool includes 10 variables with a total score ranging from 0 to 100 and a cut-off score of 31.5. In the present study, the scoring model has been validated in our multicentre cohort of 744 neonates. RESULTS In the validation cohort, this scoring model had sensitivity of 82.1%, specificity 91.7%, positive predictive value 81.2%, negative predictive value 92.2% and accuracy 88.8%. Based on the STARZ cut-off score of ≥ 31.5, an area under the receiver operating characteristic (ROC) curve was observed to be 0.932 (95% CI, 0.910-0.954; p < 0.001) signifying that the discriminative power was high. In the validation cohort, the probability of AKI was less than 20% for scores up to 32, 20-40% for scores between 33 and 36, 40-60% for scores between 37 and 43, 60-80% for scores between 44 and 49, and ≥ 80% for scores ≥ 50. CONCLUSIONS To promote the survival of susceptible neonates, early detection and prompt interventional measures based on highly evidenced research is vital. The risk of AKI in admitted neonates can be quantitatively determined by the rapid STARZ scoring system. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Sidharth Kumar Sethi
- Pediatric Nephrology, Kidney Institute, Medanta,The Medicity Hospital, Gurgaon, Haryana, 122001, India
| | - Rupesh Raina
- Pediatric Nephrology, Akron's Children Hospital, One Perkins Square, Akron, OH, 44308-1062, USA.
| | - Abhyuday Rana
- Kidney Institute, Medanta, The Medicity Hospital, Gurgaon, Haryana, 122001, India
| | | | - Abhishek Tibrewal
- Pediatric Nephrology, Akron's Children Hospital, One Perkins Square, Akron, OH, 44308-1062, USA
| | | | | | | | - Jagdish Sahoo
- Department of Neonatology, IMS & SUM Hospital, Bhubaneswar, India
| | | | - Kamran Afzal
- Department of Pediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
| | | | - Jyoti Bagla
- ESI Post Graduate Institute of Medical Science Research, Basaidarapur, New Delhi, India
| | - Sushma Krishnegowda
- JSS Hospital, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India
| | | | - Kritika Soni
- Pediatric Nephrology, Kidney Institute, Medanta,The Medicity Hospital, Gurgaon, Haryana, 122001, India
| | - Divya Sharma
- Department of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA
| | - Amrit Khooblall
- Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA
| | - Prajit Khooblall
- Department of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA
| | | | - Sanjay Wazir
- Cloudnine Hospital, Gurgaon, Haryana, 122001, India
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