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

Award Number: R01AI165946
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/24/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Malaria associated pathogenesis of chronic kidney disease (MAP-CKD) - 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 provide novel insights into mechanisms of maladaptive repair in other conditions characterized by intravascular hemolysis and AKI. The results from this study will help define the burden of CKD following AKI in low-and-middle-income countries, where 80% of global AKI deaths occur.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $507,863 )
2026	2026	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Allergy and Infectious Diseases Research	002	5	5/26/2026	NON-COMPETING CONTINUATION	$507,863
2026	2025	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Allergy and Infectious Diseases Research	000	4	3/12/2026	NON-COMPETING CONTINUATION	$0
2026	2025	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Allergy and Infectious Diseases Research	001	4	3/12/2026	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $507,863

Issue Date FY: 2025 ( Subtotal = $650,421 )
2025	2025	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Allergy and Infectious Diseases Research	001	4	8/25/2025	SUPPLEMENT FOR EXPANSION	$263,811
2025	2025	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Allergy and Infectious Diseases Research	000	4	8/22/2025	NON-COMPETING CONTINUATION	$386,610
														Subtotal = $650,421

Issue Date FY: 2024 ( Subtotal = $587,786 )
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Allergy and Infectious Diseases Research	000	3	5/13/2024	NON-COMPETING CONTINUATION	$587,786
														Subtotal = $587,786

Issue Date FY: 2023 ( Subtotal = $588,698 )
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Allergy and Infectious Diseases Research	000	2	5/9/2023	NON-COMPETING CONTINUATION	$588,698
														Subtotal = $588,698

Issue Date FY: 2022 ( Subtotal = $644,039 )
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Allergy and Infectious Diseases Research	000	1	6/24/2022	NEW	$644,039
														Subtotal = $644,039

Grand Total All Awards = $2,978,807

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

Award Number: R01AI165946

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/24/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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