Hereditary nephrotic syndrome (NS) is a childhood kidney disease that causes proteinuria—abnormal protein leaking in urine—and the progressive loss of kidney function. As many as 85% of NS patients with congenital onset and 44% with infantile onset have gene mutations. The pathogenesis of hereditary NS is poorly understood and there is no effective treatment. Studies using our cell and mouse models of NS demonstrated that a genetic mutation in kidney cells called podocytes induces proteinuria by activating a cell stress response in a cellular organelle called the endoplasmic reticulum (ER). Moreover, we have identified a novel urinary biomarker for detecting podocyte ER stress in the earliest stage of NS. The goal of this project is to translate the finding of a promising disease biomarker first identified in a mouse model to hereditary NS patients.
· Determine the role of podocyte ER stress in the pathogenesis of hereditary NS in patients carrying mutations in podocyte genes.
· Develop and validate a urinary biomarker to detect podocyte ER stress in hereditary NS patients.
Potential impact on child health
This study will elucidate molecular mechanisms underlying an important form of inherited kidney disease, hereditary NS, allowing for disease risk stratification and the development of highly targeted treatments for pediatric NS patients.