# Daily Caloric Restriction in Overweight and Obese Adults with ADPKD

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $529,413

## Abstract

Project Summary
Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder that leads to end-
stage kidney disease. To date, tolvaptan is the only approved intervention to slow kidney disease progression
in patients with ADPKD. However, tolvaptan is constrained by high cost and common side effects that limit
adherence and is only indicated for rapidly progressing ADPKD. Thus, alternative or concurrent interventions
that may slow progression of ADPKD are of considerable clinical importance. Similar to the general
population, body-mass index has been increasing in patients with ADPKD, and approximately nearly 70% of
adults with ADPKD are overweight or obese. Adipocytes do not simply act as a fat reservoir, but are active
endocrine organs, and thus, may be a promising clinical target for ADPKD management. Mounting evidence
also suggests that a metabolic defect exists in ADPKD, which likely contributes to cystic epithelial proliferation
and subsequent cyst growth. Mild-to-moderate food restriction profoundly slows cyst growth and maintains
renal function in numerous rodent models of PKD via mechanisms including activation of AMP-activated kinase
and suppression of mammalian target of rapamycin-S6 kinase signaling and insulin-like growth factor-1 levels.
Additionally, we have shown that overweight and obesity are strong independent predictors of more rapid
kidney growth, measured by total kidney volume (TKV). We recently completed a R03-funded pilot study
supporting that a behavioral weight loss intervention via daily caloric restriction (DCR) in adults with ADPKD
and overweight or obesity: 1) is feasible and acceptable; 2) slowed kidney growth (annual %∆ in height-
adjusted TKV [htTKV]); 3) reduced abdominal adiposity; and 4) altered markers of biological pathways
implicated in ADPKD progression and metabolism. However, our pilot and feasibility study was limited by a
small sample size, relatively short duration, and lack of a control group. Thus, to translate these promising
results of our pilot study towards clinical practice, we propose a parallel-group, randomized, controlled clinical
trial in 126 adults with ADPKD and overweight or obesity to directly compare the efficacy of behavioral weight
loss intervention based on DCR vs. control (standard clinical advice for ADPKD) for slowing kidney growth over
a longer duration. Changes in abdominal adiposity will serve as a secondary outcome. Effects of weight loss
on circulating and adipose markers of biological pathways will provide mechanistic insight.
Specific Aim 1: Determine the effect of a DCR-based behavioral weight loss intervention on kidney growth
(annual %∆ htTKV by MRI over 24 months) vs. control (standard clinical dietary advice for ADPKD).
Specific Aim 2: Quantify changes in abdominal adiposity (visceral, subcutaneous, and total) by MRI in each
group and their association with changes in htTKV and markers of biological pathways.
Specific Aim 3: Measure changes in ...

## Key facts

- **NIH application ID:** 10273578
- **Project number:** 1R01DK129259-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kristen Lynn Nowak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $529,413
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10273578

## Citation

> US National Institutes of Health, RePORTER application 10273578, Daily Caloric Restriction in Overweight and Obese Adults with ADPKD (1R01DK129259-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10273578. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*