Therapeutic Potential of Ketogenic Interventions for Autosomal-Dominant Polycystic Kidney Disease: A Systematic...

Recent findings have highlighted that abnormal energy metabolism is a key feature of autosomal-dominant polycystic kidney disease (ADPKD). Emerging evidence suggests that nutritional ketosis could offer therapeutic benefits, including potentially slowing or even reversing disease progression. This systematic review aims to synthesise the literature on ketogenic interventions to evaluate the impact in ADPKD.

A systematic search was conducted in Medline, Embase, and Scopus using relevant Medical Subject Headings (MeSH) and keywords. Studies assessing ketogenic interventions in the management of ADPKD in both human and animal models were selected for data extraction and analysis.

Three animal reports and six human studies were identified. Ketogenic diets (KD) significantly slowed polycystic kidney disease (PKD) progression in rats with improved renal function and reduced cystic areas. There was reduced renal fibrosis and cell proliferation. The supplementation of beta-hydroxybutyrate (BHB) in rats also reduced PKD progression in a dose-dependent manner. Human studies (n = 129) on KD in ADPKD reported consistent body mass index (BMI) reduction across trials, with an average weight loss of ∼4 kg. Improvements in blood pressure were also noted. Ketosis was achieved in varying degrees. Effects on kidney function (eGFR) were beneficial. Results for kidney volume were mixed but most studies were underpowered for this outcome. Lipid profiles showed increases in total cholesterol (∼1 mmol/L) and LDL cholesterol (∼0.4 mmol/L) in most studies. Safety concerns such as "keto flu" symptoms, elevated uric acid levels, and occasional kidney stones were noted. Overall feasibility and adherence to the KD were rated positively by most participants.

Human studies are promising; however, they have been limited by small sample sizes and short durations. Larger, long-term trials are needed to assess the efficacy, adherence, and safety of ketogenic diets in people with ADPKD.