# Kidney Tubular Damage and Dysfunction in Autosomal Dominant Polycystic Kidney Disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $649,120

## Abstract

PROJECT SUMMARY / ABSTRACT
Autosomal dominant polycystic kidney disease (ADPKD)., the most common genetic kidney disease in the
world, is characterized by progressive kidney tubule cyst growth, and after decades of tubule damage, it leads
to declining glomerular filtration rate (GFR) and kidney failure. By the time this GFR decline is detected, nearly
half the original functional glomeruli and tubules are irreversibly lost. Currently, there is no cure for ADPKD and
the vasopressin receptor antagonist tolvaptan is the only drug approved by the FDA to slow progression
Tolvaptan slows GFR decline, but is expensive, difficult to take, and has considerable side effects. There is an
unmet need to study novel tubular biomarkers in persons with ADPKD with the goal of improving early
identification and quantification of risk for progression, targeted treatment for the highest risk individuals, and
enrichment methods for future clinical trials.
 We have worked extensively to expand the paradigm of tubular function in kidney disease. We have
demonstrated the utility of a focused kidney tubule health panel (KTHP) consisting of proximal tubule injury,
tubulo-interstitial inflammation, repair and fibrosis, and secretion in the general population, and among those
with CKD, HIV, and heart failure. However, persons with ADPKD were not included in these studies, and our
preliminary data demonstrate that several of these tubule markers are particularly perturbed in APDKD. Our
goal is to develop an ADPKD-specific KTHP which will incorporate different dimensions of tubular health and
injury, improve kidney failure risk prognostication of persons, and evaluate the potential salient effects of
tolvaptan on tubular health.
 We propose to use a unique repository of biospecimens at multiple timepoints from over 2,700 persons with
ADPKD who were enrolled in the Phase 3 TEMPO 3:4 and REPRISE trials – both are placebo-controlled trials
of tolvaptan in ADPKD. In Aim 1 we will develop and compare KTHP dimensions and correlate them with
ADPKD severity, with the hypothesis that these markers will identifying ADPKD patients at highest risk for
rapid kidney disease progression, above and beyond currently available clinical and imaging measures.
Leveraging the design of the clinical trials, we will compare the effect of tolvaptan versus placebo on tubule
health markers (Aim 2). Finally, we will determine whether short-term changes in kidney tubule health
biomarkers can predict long-term progression of ADPKD (Aim 3). This comprehensive approach to
phenotypying tubular health will advance the role of tubular biomarkers in risk stratification, patient
identification, and monitoring response to treatment in ADPKD.

## Key facts

- **NIH application ID:** 10860291
- **Project number:** 1R01DK139291-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Pranav Garimella
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $649,120
- **Award type:** 1
- **Project period:** 2024-06-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10860291

## Citation

> US National Institutes of Health, RePORTER application 10860291, Kidney Tubular Damage and Dysfunction in Autosomal Dominant Polycystic Kidney Disease (1R01DK139291-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10860291. Licensed CC0.

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