Saturday, July 5, 2025 7/5/2025

Mechanisms of acute kidney injury in malaria - Resubmission - 1

Award Number: R21AI151349
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: 12/15/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2023

Group Awards By:

View Award Description

Mechanisms of acute kidney injury in malaria - Resubmission - 1 - Summary Acute kidney injury (AKI) is one of the least understood but most common complications of severe pediatric malaria and is strongly associated with increased mortality. Our previous results indicate that elevated levels of autoimmune antibodies circulating in children with severe falciparum malaria strongly correlate with parameters of kidney dysfunction. These results suggest that the pathogenesis of malaria-induced AKI could be similar to classical autoimmune diseases such as systemic lupus erythematosus, where autoimmune antibodies form immune complexes (IC) that induce kidney pathology. However, our previous work has also identified that markers of hemolysis (free-heme and hemoglobin), correlate with the development of AKI in African children. Hemolysis is a well-established cause of kidney injury, suggesting that lysis of erythrocytes induced by autoimmune antibodies may also contribute to AKI. Our overarching hypothesis is that autoimmune antibodies decisively contribute to kidney pathology in malaria. We intend to determine the relative contribution to malaria-induce kidney pathology of two possible autoantibody-induced mechanisms: (1) deposition of IC and (2) hemolysis-induced damage in the kidneys. Using mice models of malaria, we will test this hypothesis and determine the role of autoantibodies in kidney pathology. We will characterize whether IC deposition in the kidneys (aim 1.1) and/or hemolysis mediated by autoimmune antibodies (aim 1.2) are major causes of AKI during acute malaria. We will also test the role of neutrophil extracellular traps (NETs) in the formation of DNA-IC and in kidney dysfunction during malaria. In aim 2 we will characterize the relationship of autoantibodies and IC with hemolysis by analyzing the relation of the heme-axis (free-heme, hemopexin and cell-free hemoglobin, previously proposed to contribute to AKI in malaria), oxidative stress and nitric oxide bioavailability, with acute and persistent kidney dysfunction during malaria in a clinically well-characterized prospective cohort of 600 children with severe malaria followed for one year. This study will increase our understanding of kidney dysfunction in malaria both mechanistically and epidemiologically, paving the way for the finding of new biomarkers and the development of therapies.


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: 2024 ( Subtotal = $0 )
2024	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	2	7/22/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $210,408 )
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	2	11/16/2021	NON-COMPETING CONTINUATION	$210,408
														Subtotal = $210,408

Issue Date FY: 2021 ( Subtotal = $265,840 )
2021	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	12/14/2020	NEW	$265,840
														Subtotal = $265,840

Grand Total All Awards = $476,248

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms of acute kidney injury in malaria - Resubmission - 1

Award Number: R21AI151349

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: 12/15/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer