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Multicenter Study
. 2025 Jul 15;26(1):390.
doi: 10.1186/s12882-025-04333-7.

Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malaria

Anthony Batte  1   2 , Violah Nakulima  3 , Ruth Namazzi  3   4 , Judith Caroline Aujo  5 , Michelle C Starr  6 , Andrew L Schwaderer  6 , Michael Lintner-Rivera  7 , Avias Ahumwire  3 , Daniel Ogwal  3 , Emmanuel Tenywa  8 , William Oyang  9 , John M Ssenkusu  3   10 , Paul Bangirana  3   11 , Richard Idro  3   4 , Robert Kalyesubula  12 , Gavin Dreyer  13 , Mignon McCulloch  14 , Quique Bassat  2   15 , Chandy C John  7 , Stuart L Goldstein  16 , Andrea L Conroy  17   18   19
Affiliations
Multicenter Study

Malaria associated pathogenesis of chronic kidney disease (MAP-CKD): a prospective study of children hospitalized with severe malaria

Anthony Batte et al. BMC Nephrol. .

Abstract

Background: Severe malaria (SM) remains a leading cause of child mortality and an important global contributor to acute kidney injury (AKI), which can progress to chronic kidney disease (CKD) in some survivors. Notably, 80% of AKI deaths occur in low- and middle-income countries (LMIC). Despite this burden, the mechanisms and recovery trajectory of SM associated AKI remain poorly understood. There is a critical need to define the etiology and pathophysiology of SM-AKI, uncover pathways of maladaptive repair, identify risk factors for CKD, and evaluate long-term health and development.

Methods: This prospective multi-site cohort study will enroll children at three sites in Uganda: Mulago National Referral and Teaching Hospital, Jinja Regional Referral Hospital, and Lira Regional Referral Hospital. We aim to recruit 750 children with severe malaria and 375 community controls between 3 months of age and < 16 years. Participants will be followed for two years. Children with severe malaria will be assessed at 1-, 2-, and 4-months to evaluate short-term kidney recovery and 12- and 24-months to assess kidney function and health-related quality of life. The study will investigate short-term and long-term kidney disease risk factors following severe malaria. We will characterize host pathways involved in maladaptive kidney repair, focusing on mechanisms related to cell stress, angiogenesis, and tubulointerstitial injury. Additionally, we will assess the impact of AKI and persistent kidney disease on morbidity, mortality, and health-related quality of life. Cognitive and behavioral assessments, along with brain magnetic resonance imaging (MRI), will be used to evaluate the effects of AKI on brain injury and edema.

Discussion: This study will generate key insights into the prevalence of persistent kidney disease following SM-AKI and identify risk factors for CKD to inform clinical follow-up. Defining specific pathways involved with maladaptive repair in severe malaria will provide the foundation for targeted interventions to promote adaptive recovery. The research has the potential to transform long-term health outcomes following SM-AKI.

Trial registration: ISRCTN10885288.

Keywords: Acute kidney injury; Brain injury; Chronic kidney disease; Health-related quality of life; Maladaptive repair; Pediatrics; Severe malaria.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study is approved by the Makerere University School of Biomedical Sciences Research Ethics Committee (SBS-REC, protocol number: SBS-2022-173), Indiana University School of Medicine Institutional Review Board (IUSM- IRB, protocol number: 15144) and the Uganda National Council for Science and Technology (UNCST, protocol number: HS2794ES). The study will be conducted in accordance with legal and regulatory requirements, as well as the general principles outlined in the International Ethical Guidelines for Biomedical Research Involving Human Participants and the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Primary and secondary exposures and outcomes. Table depicting primary (yellow) and secondary (pink) exposures and outcomes for the study with their accompanying definitions
Fig. 2
Fig. 2
Participant enrolment flow chart. Proposed enrollment flow chart for children with severe malaria and community children
See this image and copyright information in PMC

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