Acute kidney injury, persistent kidney disease, and post-discharge morbidity and mortality in severe malaria in children: A prospective cohort study.

Ruth Namazzi,Andrea L Conroy,Anthony Batte,Chandy C John,Robert O Opoka,John M Ssenkusu,Zachary Berrens,Stuart L Goldstein,Andrew L Schwaderer,Paul Bangirana,Dibyadyuti Datta,Michael Goings

doi:10.1016/j.eclinm.2022.101292

Abstract

SummaryBackgroundGlobally, 85% of acute kidney injury (AKI) cases occur in low-and-middle-income countries. There is limited information on persistent kidney disease (acute kidney disease [AKD]) following severe malaria-associated AKI.MethodsBetween March 28, 2014, and April 18, 2017, 598 children with severe malaria and 118 community children were enrolled in a two-site prospective cohort study in Uganda and followed up for 12 months. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to define AKI (primary exposure) and AKD at 1-month follow-up (primary outcome). Plasma neutrophil gelatinase-associated lipocalin (NGAL) was assessed as a structural biomarker of AKI.FindingsThe prevalence of AKI was 45·3% with 21·5% of children having unresolved AKI at 24 h. AKI was more common in Eastern Uganda. In-hospital mortality increased across AKI stages from 1·8% in children without AKI to 26·5% with Stage 3 AKI (p < 0·0001). Children with a high-risk plasma NGAL test were more likely to have unresolved AKI (OR, 7·00 95% CI 4·16 to 11·76) and die in hospital (OR, 6·02 95% CI 2·83 to 12·81). AKD prevalence was 15·6% at 1-month follow-up with most AKD occurring in Eastern Uganda. Risk factors for AKD included severe/unresolved AKI, blackwater fever, and a high-risk NGAL test (adjusted p < 0·05). Paracetamol use during hospitalization was associated with reduced AKD (p < 0·0001). Survivors with AKD post-AKI had higher post-discharge mortality (17·5%) compared with children without AKD (3·7%).InterpretationChildren with severe malaria-associated AKI are at risk of AKD and post-discharge mortality.FundingThis work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke (R01NS055349 to CCJ) and the Fogarty International Center (D43 TW010928 to CCJ), and a Ralph W. and Grace M. Showalter Young Investigator Award to ALC.

Highlights

acute kidney injury (AKI) is a risk factor for mortality, new disabilities at discharge, cognitive and behavioral problems, and chronic kidney disease (CKD) in surviving children.3−7 AKI is increasingly recognized in children with severe malaria, the burden of malaria-associated AKI in low-and-middle-income countries (LMIC) and its impact on lifelong health outcomes, including CKD, remains poorly understood
We evaluated risk factors for AKI and acute kidney disease (AKD) to define the impact of persistent kidney disease on morbidity and mortality in the context of severe malaria
Setting Children with severe malaria or community children were recruited from Mulago National Referral and Teaching Hospital (MNRH) in Kampala in Central Uganda and Jinja Regional Referral Hospital (JRRH) in Eastern Uganda (Figure 1)

Summary

Introduction

In low-and-middle-income countries (LMIC), there are an estimated 18 million acute kidney injury (AKI) cases annually, representing 85% of global cases. In contrast to high-income countries, AKI in LMIC is more often community-acquired and occurs in previously healthy children. AKI is a risk factor for mortality, new disabilities at discharge, cognitive and behavioral problems, and chronic kidney disease (CKD) in surviving children.− AKI is increasingly recognized in children with severe malaria (reviewed in4), the burden of malaria-associated AKI in LMIC and its impact on lifelong health outcomes, including CKD, remains poorly understood.AKI and CKD are interconnected syndromes linked by a transitional period called acute kidney disease (AKD). AKD represents acute or subacute damage or loss of kidney function between 7 and 90 days after exposure to an AKI initiating event. Conceptually, AKD represents persistent kidney injury in the postAKI period and offers an opportunity to intervene and positively modify long-term outcomes associated with CKD. Risk factors for AKD include severe, persistent, or relapsing AKI. In low-and-middle-income countries (LMIC), there are an estimated 18 million acute kidney injury (AKI) cases annually, representing 85% of global cases.. AKI is a risk factor for mortality, new disabilities at discharge, cognitive and behavioral problems, and chronic kidney disease (CKD) in surviving children.− AKI is increasingly recognized in children with severe malaria (reviewed in4), the burden of malaria-associated AKI in LMIC and its impact on lifelong health outcomes, including CKD, remains poorly understood. AKI and CKD are interconnected syndromes linked by a transitional period called acute kidney disease (AKD).. AKD represents persistent kidney injury in the postAKI period and offers an opportunity to intervene and positively modify long-term outcomes associated with CKD.. Additional tools to stratify patients at risk of persistent AKI, AKD, and CKD include markers of structural kidney injury, including neutrophil gelatinase-associated lipocalin (NGAL).− Because of the rising global burden of CKD and its associated strain on health systems, as well as the historical under-representation of sub-Saharan African in global AKI research, there is a critical need to define AKI recovery and predictors of AKD in malaria

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