Weight loss and cystic disease progression in autosomal dominant polycystic kidney disease

Katharina Hopp; Victoria A Catenacci; Nidhi Dwivedi; Timothy L Kline; Wei Wang; Zhiying You; Dustin T Nguyen; Kristen Bing; Bhavya Poudyal; Ginger C Johnson; Matthew R Jackman; Marsha Miller; Cortney N Steele; Natalie J Serkova; Paul S MacLean; Raphael A Nemenoff; Berenice Gitomer; Michel Chonchol; Kristen L Nowak

doi:10.1016/j.isci.2021.103697

Weight loss and cystic disease progression in autosomal dominant polycystic kidney disease

iScience. 2021 Dec 27;25(1):103697. doi: 10.1016/j.isci.2021.103697. eCollection 2022 Jan 21.

Authors

Katharina Hopp^{1

2}, Victoria A Catenacci³, Nidhi Dwivedi¹, Timothy L Kline^{4

5}, Wei Wang¹, Zhiying You¹, Dustin T Nguyen¹, Kristen Bing³, Bhavya Poudyal⁴, Ginger C Johnson³, Matthew R Jackman³, Marsha Miller³, Cortney N Steele¹, Natalie J Serkova⁶, Paul S MacLean³, Raphael A Nemenoff^{1

2}, Berenice Gitomer¹, Michel Chonchol^{1

2}, Kristen L Nowak¹

Affiliations

¹ Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
² Consortium for Fibrosis Research and Translation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
³ Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁴ Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN 55901, USA.
⁵ Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN 55901, USA.
⁶ Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Abstract

Progression of autosomal dominant polycystic kidney disease (ADPKD) is modified by metabolic defects and obesity. Indeed, reduced food intake slows cyst growth in preclinical rodent studies. Here, we demonstrate the feasibility of daily caloric restriction (DCR) and intermittent fasting (IMF) in a cohort of overweight or obese patients with ADPKD. Clinically significant weight loss occurred with both DCR and IMF; however, weight loss was greater and adherence and tolerability were better with DCR. Further, slowed kidney growth correlated with body weight and visceral adiposity loss independent of dietary regimen. Similarly, we compared the therapeutic efficacy of DCR, IMF, and time restricted feeding (TRF) using an orthologous ADPKD mouse model. Only ADPKD animals on DCR lost significant weight and showed slowed cyst growth compared to ad libitum, IMF, or TRF feeding. Collectively, this supports therapeutic feasibility of caloric restriction in ADPKD, with potential efficacy benefits driven by weight loss.

Keywords: Activities of daily living; Nephrology; Nutrition related to disease.

Abstract

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