Mounting evidence suggests that a metabolic defect exists in autosomal dominant polycystic kidney disease (ADPKD), which likely contributes to cystic epithelial proliferation and subsequent cyst growth. There are notable overlapping features and pathways among metabolism, obesity, and/or ADPKD. The investigators recently reported that in the Halt Progression of Polycystic Kidney Disease (HALT-PKD) Study A that overweight and obesity are strong independent predictors of more rapid kidney growth. Moving beyond body mass index, the investigators have novel preliminary data using magnetic resonance images (MRIs) from a small number of participants from HALT-PKD Study A that abdominal adiposity is an independent predictor of kidney growth and kidney function decline. Adipocytes do not simply act as a fat reservoir but are active endocrine organs that promote release of pro-inflammatory cytokines and produce adipokines. Numerous signaling pathways promoted by adipocytes are also implicated in cystogenesis. Periods of fasting may counter adiposity-mediated signaling pathways and slow ADPKD progression. Mild-to-moderate food restriction profoundly slows cyst growth and maintains renal function in rodent models of ADPKD, which are characterized by metabolic reprogramming favoring enhanced aerobic glycolysis. Notably, fasting promotes a shift from carbohydrate to fat metabolism, which could suppress cyst growth. The investigators are currently conducting an ongoing behavioral weight loss pilot trial (based on either daily caloric restriction or intermittent fasting) in adults with ADPKD who are overweight/obese. As an alternative to these approaches, time-restricted feeding (TRF) is a novel fasting regimen that restricts eating to a feeding window (typically 8-12 hrs/day). As isocaloric TRF reduces disease progression in a rodent model of ADPKD, including kidney: body weight and mammalian target of rapamycin (mTOR) activity, it may be an alternative and easier to adhere to dietary strategy to slow ADPKD progression. Specific Aim: Determine the feasibility of TRF without energy intake restriction in adults with ADPKD and overweight/obesity. The study will determine adherence to TRF by assessing the percent of participants achieving the goal of eating within an 8-hour TRF window, measured objectively with a photographic food record and verified with continuous glucose monitoring data. The study will also further assess the safety, acceptability, and tolerability of TRF by evaluation of safety labs, adverse events, and quality of life measures, as well as changes in abdominal adiposity and total kidney volume (TKV) by magnetic resonance imaging (MRI), and markers of biological pathways (AMP-activated protein kinase [AMPK], mTOR, insulin-like growth factor 1 [IGF1]).
The proposed research will determine the feasibility of a time restricted feeding intervention,a fasting regimen that restricts eating to a feeding window (8 hrs/day) for 1 year in adults with autosomal dominant polycystic kidney disease (ADPKD) who are overweight or obese. The study will provide valuable information on the intervention in terms of safety, adherence, acceptability, and tolerability. Last, this pilot trial will provide initial insight into biological changes including abdominal adiposity, changes in kidney growth and function, and markers of biological pathways related to the intervention.