Acute kidney injury is associated with impaired cognition and chronic kidney disease in a prospective cohort of children with severe malaria

Andrea L Conroy,Dibyadyuti Datta,Paul Bangirana,Robert O Opoka,Chandy C John,John M Ssenkusu,Catherine Morgan,Richard Idro,James S Hodges

doi:10.1186/s12916-019-1332-7

Abstract

BackgroundAcute kidney injury (AKI) is a recognized complication of pediatric severe malaria, but its long-term consequences are unknown.MethodsUgandan children with cerebral malaria (CM, n = 260) and severe malaria anemia (SMA, n = 219) or community children (CC, n = 173) between 1.5 and 12 years of age were enrolled in a prospective cohort study. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to retrospectively define AKI and chronic kidney disease (CKD). Cognitive testing was conducted using the Mullen Scales of Early Learning in children < 5 and Kaufman Assessment Battery for Children (K-ABC) second edition in children ≥ 5 years of age.ResultsThe prevalence of AKI was 35.1%, ranging from 25.1% in SMA to 43.5% in CM. In-hospital mortality was 11.9% in AKI compared to 4.2% in children without AKI (p = 0.001), and post-discharge mortality was 4.7% in AKI compared to 1.3% in children without AKI (p = 0.030) corresponding to an all-cause adjusted hazard ratio of 2.30 (95% CI 1.21, 4.35). AKI was a risk factor for short- and long-term neurocognitive impairment. At 1 week post-discharge, the frequency of neurocognitive impairment was 37.3% in AKI compared to 13.5% in children without AKI (adjusted odds ratio (aOR) 2.31 [95% CI 1.32, 4.04]); at 1-year follow-up, it was 13.3% in AKI compared to 3.4% in children without AKI (aOR 2.48 [95% CI 1.01, 6.10]), and at 2-year follow-up, it was 13.0% in AKI compared to 3.4% in children without AKI (aOR 3.03 [95% CI 1.22, 7.58]). AKI was a risk factor for CKD at 1-year follow-up: 7.6% of children with severe malaria-associated AKI had CKD at follow-up compared to 2.8% of children without AKI (p = 0.038) corresponding to an OR of 2.81 (95% CI 1.02, 7.73). The presenting etiology of AKI was consistent with prerenal azotemia, and lactate dehydrogenase as a marker of intravascular hemolysis was an independent risk factor for AKI in CM and SMA (p < 0.0001). In CM, AKI was associated with the presence and severity of retinopathy (p < 0.05) and increased cerebrospinal fluid albumin suggestive of blood-brain barrier disruption.ConclusionsAKI is a risk factor for long-term neurocognitive impairment and CKD in pediatric severe malaria.

Highlights

Acute kidney injury (AKI) is a recognized complication of pediatric severe malaria, but its long-term consequences are unknown
Infection with Plasmodium falciparum is a significant cause of global morbidity and mortality: an estimated 219 million cases of malaria were reported in 2017 with 92% of estimated cases occurring in sub-Saharan Africa [1]
Children with cerebral malaria (CM) had a 2.37-fold increase in the odds of severe AKI (AKI stage 2 or 3) compared to children with severe malarial anemia (SMA) (p = 0.010)

Summary

Introduction

Acute kidney injury (AKI) is a recognized complication of pediatric severe malaria, but its long-term consequences are unknown. Severe malaria is a leading cause of acquired neurodisability in African children [2]. Clinical risk factors described to date for neurocognitive impairment in severe malaria are acute neurologic manifestations, e.g., duration of coma and number of seizures [2,3,4,5,6]. Acute kidney injury (AKI) is a common complication of pediatric severe malaria [9, 10] associated with mortality [9,10,11,12,13] and neurologic deficits in survivors [10]. There are no data on whether AKI in severe malaria is a risk factor for CKD

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