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
Affiliations
Katharina Hopp
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Consortium for Fibrosis Research and Translation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Corresponding author
Victoria A. Catenacci
Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Nidhi Dwivedi
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Timothy L. Kline
Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN 55901, USA; Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN 55901, USA
Wei Wang
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Zhiying You
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Dustin T. Nguyen
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Kristen Bing
Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Bhavya Poudyal
Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN 55901, USA
Ginger C. Johnson
Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Matthew R. Jackman
Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Marsha Miller
Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Cortney N. Steele
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Natalie J. Serkova
Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Paul S. MacLean
Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Raphael A. Nemenoff
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Consortium for Fibrosis Research and Translation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Berenice Gitomer
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Michel Chonchol
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Consortium for Fibrosis Research and Translation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Kristen L. Nowak
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Corresponding author
Summary: 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.
