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

Active Project Grant Awarded Last action

Award ID
R01AI165946
Recipient
Awarding agency
Obligated
$5,544,734

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 88% complete
Place of performance
Indianapolis, IN 46202, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

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.

Transactions

Action Obligated Date
Amendment $174,906
Amendment $507,863
Amendment $507,863
Amendment $0
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Amendment $263,811
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Amendment $386,610
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Amendment $587,786
Amendment $588,698
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Amendment $644,039
Original award $644,039
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Subawards

Subrecipient Amount Awarded
Centre For Global Health And Child Development Kenya The work to be covered will include study implementation, day-to-day operations including regulatory oversight, ongoing data entry and data cleaning, submitting… $438,717
Global Health Uganda LIMITED The work to be covered will include study implementation, collaboration establishment, and day-to-day operations including regulatory oversight, training of… $211,212
Global Health Uganda LIMITED The work to be covered will include study implementation, collaboration establishment, and day-to-day operations including regulatory oversight, training of… $211,211
Childrens Hospital Medical Center Stuart Goldstein, M.D. will serve as the site PI for Cincinnati Children’s Hospital Medical Center. He is Cincinnati Children’s Director of the Center for Acute… $61,247
Global Health Uganda LIMITED The work to be covered will include study implementation, collaboration establishment, and day-to-day operations including regulatory oversight, training of… $221,364
Global Health Uganda LIMITED The work to be covered will include study implementation, collaboration establishment, and day-to-day operations including regulatory oversight, training of… $221,363

Quick answers

Who received award R01AI165946?

R01AI165946 was awarded to Trustees Of Indiana University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on June 24, 2022.

How much is award R01AI165946 worth?

$5,544,734 has been obligated on R01AI165946.

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