Chronic Kidney Disease (CKD) affects 15% of the US adult population 30 and vasopressin is associated with progression of non-diabetic, diabetic, and polycystic kidney disease (PKD). 1-18 However, the specific mechanism(s) through which vasopressin worsens progression of kidney disease are unclear. Vasopressin is the biologically active end-product of a 164 amino acid pre- pro-peptide and physiologic production is currently thought to be limited to the brain. We recently found that vasopressin is also made in the kidney under physiologic conditions and expression is increased in PKD in both humans and mice. Therefore, the aim of this project is to understand the function, regulation, and impact of kidney-derived vasopressin in health and disease. We have preliminary data that show that mice that lack kidney-derived vasopressin in the distal nephron have altered water balance. We propose to (1) determine the mechanism through which kidney-derived vasopressin influences water balance and (2) determine if kidney- derived vasopressin is involved cyst growth and progression of PKD. Successful completion of this project will help clarify the mechanism(s) through which the interplay between local and systemic vasopressin signaling impacts kidney disease, potentially identifying new therapeutic targets and approaches for CKD and PKD. Work will occur in one of the largest and most scientifically diverse nephrology divisions in the world, within the Vanderbilt University Medical Center Department of Medicine. This project has already received extensive external (Harold Amos Medical Faculty Development Award – 2020) and institutional support in the form of financial support and a comprehensive career development plan involving internal and external mentorship, workshops, and coursework.

Vasopressin is a hormone that regulates water balance, blood pressure and contributes to progression of non-diabetic, diabetic, and polycystic kidney disease (PKD), through mechanisms that are still unclear. Vasopressin production was thought to be limited to the brain, but we have evidence that it is also made in the kidney. This project aims to understand the role that kidney-derived vasopressin plays in health and disease using cells and transgenic mouse models with a targeted deletion of vasopressin in the kidney.