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Kidney Week

Abstract: PO1251

Weight Loss to Slow Cyst Growth in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Nowak, Kristen L., University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Catenacci, Victoria, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Kline, Timothy L., Mayo Clinic College of Medicine and Science, Rochester, Minnesota, United States
  • Wang, Wei, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • You, Zhiying, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Bing, Kristen, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Poudyal, Bhavya, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, United States
  • Steele, Cortney, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Chonchol, Michel, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Gitomer, Berenice Y., University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
Background

Recent studies in animal models of ADPKD support that food restriction can profoundly slow cyst growth and maintain renal function. We have also reported that overweight and obesity are strong independent predictors of ADPKD progression. Thus, it is plausible that weight loss, caloric restriction, and/or periods of fasting may slow ADPKD progression in humans; however, the feasibility of these dietary interventions, and whether the driver of therapeutic efficacy is periods of fasting or reduction in body weight, is unknown.

Methods

We conducted a one-year study evaluating feasibility of delivery of a behavioral weight loss intervention based on either daily caloric restriction (DCR) or intermittent fasting (IMF) in adults with overweight/obesity, ADPKD, and eGFR ≥30 m/min/1.73m2 (targeted weekly energy deficit of ~34% in both groups). We also evaluated the safety, acceptability, and tolerability of each intervention, and obtained exploratory insight into changes height-corrected total kidney volume (htTKV).

Results

28 participants (16F/12M; 46±9 yrs, body mass index 34.7±5.0 kg/m2, eGFR of 69±22 m/min/1.73m2) were randomized to either DCR (n=15) or IMF (n=13). Clinically significant (>5%) weight loss was achieved in both groups at month 3 (DCR: -7.1±4.2%; IMF: -5.5±3.3%). At 12 months DCR lost additional weight while weight loss in IMF plateaued (DCR: -9.1±6.0%; IMF: 4.9±5.6%; p<0.05 DCR vs. IMF). Overall, DCR had a more favorable safety, tolerability, and adherence profile than IMF. Annual htTKV %△ was qualitatively low in both groups in comparison to historical data, despite comparable clinical characteristics (DCR: 1.5±3.4%, IMF: 1.7±6.1%). Annual htTKV %△ was highly correlated with %△ in weight (r = 0.68, p=0.001). Abdominal saturated adipose tissue (SAT), visceral adipose tissue (VAT) and total adipose tissue (TAT) quantified by MRI were all reduced at one year (p<0.05). Change in VAT (r = 0.49, p<0.05) and TAT (r = 0.46, p<0.05) also correlated with annual htTKV %△.

Conclusion

IMF, and particularly DCR, were feasible interventions over a one-year period in adults with ADPKD and overweight/obesity and showed favorable effects on kidney growth as compared to historical controls, supporting conduction of a phase II randomized controlled trial.

Funding

  • NIDDK Support