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

Objectives

The main objective of this project is to evaluate the malaria-associated pathogenesis (MAP) of acute and chronic kidney disease (CKD) after severe malaria.

Two specific aims will be pursued to evaluate the malaria-associated pathogenesis of acute and chronic kidney disease (MAP-CKD) after severe malaria.

1. Aim 1: the project will determine the 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. Also the genetic risk factors for CKD in children over follow-up will be evaluated, focusing on genes linked to kidney disease (e.g., APOL1) or protection from severe malaria (e.g., sickle cell anemia).
2. Aim 2: the focus will be 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.

The long-term goal of this project 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, the 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.