Long-term mortality and risk of chronic kidney disease in children following severe malaria complicated by acute kidney injury: a prospective observational study.
Children with AKI following severe malaria face increased long-term mortality, underscoring the need for improved post-acute care strategies in malaria-endemic areas.
Where it sits
this study against the rest of the semax corpusSummary and findings
This study evaluated long-term outcomes in Ugandan children with severe malaria complicated by acute kidney injury (AKI). It found that AKI was associated with increased long-term mortality and risk of chronic kidney disease (CKD). The analysis included 1077 children, with a median follow-up of 6.5 years.
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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).<h4>Interpretation</h4>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.<h4>Funding</h4>The US National Institute of Neurological Disorders and Stroke, the Fogarty International Center, the US National Institutes of Allergy and Infectious Diseases, and a Ralph W and Grace M Showalter Young Investigator Award.
Background
The study addresses the long-term impact of paediatric acute kidney injury (AKI) following severe malaria, a complication with poorly defined outcomes in low-income and middle-income countries. Previous research has established AKI as a significant complication of severe malaria, but its long-term effects on mortality and kidney health remain unclear. This study aims to fill this gap by evaluating these outcomes in a cohort of Ugandan children.
Methods
The study pooled data from two prospective cohorts of Ugandan children aged 6 months to 12 years admitted with severe malaria between 2008 and 2017. Children with available blood samples for creatinine measurement were included. Surviving participants were followed from 2020 to 2023 to assess kidney function and survival. Cox regression modeled mortality risk, while logistic regression estimated odds of CKD and major adverse kidney events.
Results
At enrolment, 40.0% of the 1077 children had AKI. Over a median follow-up of 6.5 years, 13.6% of children died, with nearly half of the deaths occurring post-discharge. The adjusted odds of major adverse kidney events were significantly higher in children with AKI (aOR 3.14, 95% CI 2.23-4.43). The mortality risk remained elevated beyond 2 years after the acute episode (aHR 4.53, 95% CI 1.80-11.37). AKI survivors had higher odds of CKD, but this was not statistically significant after adjustment (aOR 1.47, 95% CI 0.84-2.56; p=0.18).
Interpretation
The study suggests that AKI in children with severe malaria is associated with increased long-term mortality, indicating that AKI may be a marker of ongoing vulnerability. The findings highlight the limitations of current acute-care models in malaria-endemic regions. However, the observational nature of the study limits causal conclusions, and the clinical significance of the findings should be interpreted cautiously.
Key findings
- 431 (40.0%) children had AKI at enrolment.
- 147 (13.6%) of children died over a median of 6.5 years.
- Adjusted odds of major adverse kidney events were 3.14 (95% CI 2.23-4.43) for AKI survivors.
- Adjusted hazard ratio for mortality risk was 3.36 (95% CI 2.22-5.10) for AKI survivors.
- AKI survivors had higher odds of CKD (odds ratio 1.77, 95% CI 1.07-2.93).
Limitations
- Observational study design
- Potential for unmeasured confounding
- Follow-up may not capture all long-term outcomes
- Results may not be generalizable beyond the study population