Long-term mortality and risk of chronic kidney disease in children following severe malaria complicated by acute kidney injury: a prospective observational study
Abstract
Background: Paediatric acute kidney injury (AKI) is a complication of severe malaria, but its long-term outcomes remain poorly defined in low-income and middle-income countries. We aimed to evaluate the long-term association between paediatric AKI and kidney outcomes and mortality following severe malaria.
Methods: We pooled data from two prospective cohorts of Ugandan children (ie, those aged 6 months–12 years) admitted to hospital with severe malaria between 2008 and 2017. Children with stored admission blood samples available for creatinine measurement were included in the analysis. Surviving participants were enrolled in a follow-up study conducted from 2020 to 2023, when kidney function and survival were assessed, using Cox regression with age as the timescale to model mortality risk. Logistic regression was used to estimate the odds of chronic kidney disease (CKD), defined as two or more consecutive low estimated glomerular filtration rates 90 days or more apart, and long-term major adverse kidney events, defined as CKD or death. Adjusted analyses included the following enrolment characteristics: age, sex, height-for-age Z score, study site, study cohort, severe malaria group (ie, cerebral malaria, severe malarial anaemia, respiratory distress, complicated seizures, or prostration), and HIV status.
Findings: At enrolment, the median age was 2·5 years (IQR 1·8–3·5), 622 (57·8%) of 1077 were male and 455 (42·2%) were female, with Kidney Disease: Improving Global Outcomes-defined AKI occurring in 431 (40·0%) children. Over a median of 6·5 years (3·7–8·8), 147 (13·6%) of children died, with nearly half of deaths (71 of 147) occurring after hospital discharge. Adjusted odds of long-term major adverse kidney events were higher among children with AKI (adjusted odds ratio [aOR] 3·14, 95% CI 2·23–4·43), driven by a higher mortality risk (adjusted hazard ratio [aHR] 3·36, 95% CI 2·22–5·10) that remained elevated beyond 2 years after the acute episode (aHR 4·53, 1·80–11·37). AKI survivors had higher odds of chronic kidney disease over follow-up (odds ratio 1·77, 1·07–2·93), although not significant after adjustment (aOR 1·47, 95% CI 0·84–2·56; p=0·18).
Interpretation: In this paediatric population, AKI was associated with excess long-term mortality, suggesting AKI is a sentinel event that marks sustained vulnerability to death and highlights limitations of acute-care models in malaria-endemic settings.
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BibTeX
@article{mellencamp2026longterm,
title = {{Long-term mortality and risk of chronic kidney disease in children following severe malaria complicated by acute kidney injury: a prospective observational study}},
author = {Kagan A Mellencamp and Ruth Namazzi and Anthony Batte and Caroline Kazinga and Claire D Liepmann and Michael J Goings and Robert O Opoka and Dibyadyuti Datta and Jie Ren and Robert Kalyesubula and Paul Bangirana and Stuart L Goldstein and Chandy C John and Andrea L Conroy},
journal = {The Lancet. Global health},
year = {2026},
month = aug,
doi = {10.1016/j.langlo.2026.103984},
url = {https://doi.org/10.1016/j.langlo.2026.103984},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Long-term mortality and risk of chronic kidney disease in children following severe malaria complicated by acute kidney injury: a prospective observational study
AU - Kagan A Mellencamp
AU - Ruth Namazzi
AU - Anthony Batte
AU - Caroline Kazinga
AU - Claire D Liepmann
AU - Michael J Goings
AU - Robert O Opoka
AU - Dibyadyuti Datta
AU - Jie Ren
AU - Robert Kalyesubula
AU - Paul Bangirana
AU - Stuart L Goldstein
AU - Chandy C John
AU - Andrea L Conroy
PY - 2026
DA - 2026/08/10
JO - The Lancet. Global health
DO - 10.1016/j.langlo.2026.103984
UR - https://doi.org/10.1016/j.langlo.2026.103984
AB - Background: Paediatric acute kidney injury (AKI) is a complication of severe malaria, but its long-term outcomes remain poorly defined in low-income and middle-income countries. We aimed to evaluate the long-term association between paediatric AKI and kidney outcomes and mortality following severe malaria. Methods: We pooled data from two prospective cohorts of Ugandan children (ie, those aged 6 months–12 years) admitted to hospital with severe malaria between 2008 and 2017. Children with stored admission blood samples available for creatinine measurement were included in the analysis. Surviving participants were enrolled in a follow-up study conducted from 2020 to 2023, when kidney function and survival were assessed, using Cox regression with age as the timescale to model mortality risk. Logistic regression was used to estimate the odds of chronic kidney disease (CKD), defined as two or more consecutive low estimated glomerular filtration rates 90 days or more apart, and long-term major adverse kidney events, defined as CKD or death. Adjusted analyses included the following enrolment characteristics: age, sex, height-for-age Z score, study site, study cohort, severe malaria group (ie, cerebral malaria, severe malarial anaemia, respiratory distress, complicated seizures, or prostration), and HIV status. Findings: At enrolment, the median age was 2·5 years (IQR 1·8–3·5), 622 (57·8%) of 1077 were male and 455 (42·2%) were female, with Kidney Disease: Improving Global Outcomes-defined AKI occurring in 431 (40·0%) children. Over a median of 6·5 years (3·7–8·8), 147 (13·6%) of children died, with nearly half of deaths (71 of 147) occurring after hospital discharge. Adjusted odds of long-term major adverse kidney events were higher among children with AKI (adjusted odds ratio [aOR] 3·14, 95% CI 2·23–4·43), driven by a higher mortality risk (adjusted hazard ratio [aHR] 3·36, 95% CI 2·22–5·10) that remained elevated beyond 2 years after the acute episode (aHR 4·53, 1·80–11·37). AKI survivors had higher odds of chronic kidney disease over follow-up (odds ratio 1·77, 1·07–2·93), although not significant after adjustment (aOR 1·47, 95% CI 0·84–2·56; p=0·18). Interpretation: In this paediatric population, AKI was associated with excess long-term mortality, suggesting AKI is a sentinel event that marks sustained vulnerability to death and highlights limitations of acute-care models in malaria-endemic settings.
SN - 2214-109X
ER -