# Kidney Stone Disease In ADPKD

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $436,789

## Abstract

ABSTRACT/SUMMARY
Autosomal dominant polycystic kidney (ADPKD) affects an estimated 600,000 individuals in the US and
accounts for 5% of patients with end-stage kidney disease (ESKD). At the current time there is only one
approved therapy available for patients diagnosed with rapidly progressing disease. This underlines the need
for identification of additional measures to slow kidney disease progression in ADPKD patients. Kidney stone
disease is highly prevalent, increasingly common, and associated with considerable comorbidity among
patients affected with ADPKD. In this proposal, we build on our preliminary data which demonstrates that
patients with ADPKD and kidney stone disease have a more rapid loss of kidney function compared to ADPKD
patients without kidney stone disease. We will leverage an interdisciplinary team that is uniquely poised to
define kidney stone disease in ADPKD by combining expertise in large data analytics and high-dimensional
microbiome and metabolomic data. The overall goal of this application is to demonstrate that kidney stone
disease in patients with ADPKD represents a significant risk factor for faster kidney disease progression and
that antibiotic exposure increases stone risk in this population. A secondary goal is to determine how dysbiosis
of the gut microbiome contributes to kidney stone disease. We hypothesize that kidney stone disease
contributes to more rapid decline in kidney function in ADPKD through worsening inflammation and that
antibiotics contribute to kidney stone disease by perturbing the gut-PKD axis through alterations of the gut
microbiome. We test this hypothesis in 3 specific aims. In aim 1, we seek to describe the distribution and
composition of kidney stones by sex and age and to determine the link between kidney stone disease and
decline in kidney function independent of markers of inflammation and other known risk factors for kidney
disease progression. In Aim 2 we investigate the link between antibiotic exposure and kidney stone disease
while in Aim 3 we will define the link between oral antibiotic exposure and change in urinary kidney stone risk
factors resultant from changes in the microbiome. We will leverage the Intermountain Healthcare System
database with medical and pharmacy coverage, and clinical data including stone analysis and the longitudinal
data and samples from the NIDDK sponsored HALT-PKD clinical trials. These resources will provide access to
1,823 patients with ADPKD including 296 with kidney stones. We will recruit 100 patients with ADPKD with or
without antibiotic exposure to facilitate microbiome and stone risk analysis in aim 3. A barrier to developing
new therapies for stone prevention is a lack of understanding of how perturbations of the gut microbiome and
downstream metabolite changes in the intestinal and urinary tracts contributes to kidney stone disease.
Understanding the gut-PKD axis from the proposed studies will introduce a new paradigm for kidney stone
preven...

## Key facts

- **NIH application ID:** 10491989
- **Project number:** 5R01DK128842-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Michel Benjamin Chonchol
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $436,789
- **Award type:** 5
- **Project period:** 2021-09-22 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491989

## Citation

> US National Institutes of Health, RePORTER application 10491989, Kidney Stone Disease In ADPKD (5R01DK128842-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10491989. Licensed CC0.

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