# Malaria associated pathogenesis of chronic kidney disease (MAP-CKD)

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $644,039

## Abstract

PROJECT SUMMARY/ABSTRACT
Acute kidney injury (AKI) is an abrupt loss of kidney function that occurs in 25-59% of children hospitalized with
severe malaria. AKI is one of the strongest risk factors for death in children with severe malaria and is associated
with long-term cognitive and kidney problems. Following injury, the kidney undergoes a repair process to restore
normal kidney function. If the repair process goes awry and is ‘maladaptive’, it can lead to persistent kidney injury
and chronic kidney disease (CKD). Our previous studies showed an increased risk of CKD in severe malaria
survivors. These results led to our central hypothesis that persistent activation of pathways associated with
severe malaria associated-AKI contributes to maladaptive repair following AKI and increases CKD risk. Towards
this hypothesis, we have preliminary data showing that persistent immune activation and signs of altered blood
vessel function are associated with persistent kidney disease at one-month follow-up. An estimated 15.6% of
Ugandan children have persistent kidney injury after severe malaria with 17.5% of children with persistent kidney
injury dying within one-year follow-up compared to 3.7% without AKI. Guided by strong preliminary data, we
propose a prospective multi-site observational cohort study to follow 750 Ugandan children, 90 days to 15 years
of age, hospitalized with severe malaria to assess the incidence of CKD. We will also enroll 189 community
children of the same age to define the incidence of CKD in Ugandan children. We will pursue two Specific Aims
to evaluate the malaria-associated pathogenesis of acute and chronic kidney disease (MAP-CKD) after severe
malaria. In Aim 1, we will determine clinical risk factors associated with CKD, including the severity and duration
of AKI as well as a poorly understood complication of malaria called blackwater fever. We will also evaluate the
genetic risk factors for CKD in children over follow-up, focusing on genes linked to kidney disease (e.g., APOL1)
or protection from severe malaria (e.g., sickle cell anemia). In Aim 2, we will focus on defining mechanisms of
maladaptive repair following AKI by measuring biomarkers in children’s blood and urine over follow-up. These
studies will have the potential to uncover pathways of maladaptive repair following AKI that lead to the
development of CKD and are amenable to intervention. Our long-term goal is to prevent children from developing
CKD. These studies will achieve this goal by allowing us to identify children at the highest risk of CKD, providing
clinical follow-up and early treatment for CKD. Secondly, by determining the maladaptive nature of the healing
process, we will be able to use biomarkers to identify children at risk of CKD. Third, these studies have the
potential to identify treatments to promote adaptive renal repair and reduce CKD development. Collectively, our
proposed research will provide new insights into kidney disease in malaria and may...

## Key facts

- **NIH application ID:** 10522245
- **Project number:** 1R01AI165946-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Andrea L. Conroy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $644,039
- **Award type:** 1
- **Project period:** 2022-06-24 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522245

## Citation

> US National Institutes of Health, RePORTER application 10522245, Malaria associated pathogenesis of chronic kidney disease (MAP-CKD) (1R01AI165946-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10522245. Licensed CC0.

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