Ketogenic dietary interventions for autosomal-dominant polycystic kidney disease (ADPKD): a systematic review and synthesis without meta-analysis (SWiM) of observational and interventional studies

The purpose of this systematic review was to synthesize available human studies, present and weigh the evidence regarding the efficacy of ketogenic dietary interventions (KDIs) for ADPKD, to provide a direction for future research and relevant recommendations. Three databases were searched and risk of bias (RoB) of the studies was assessed using Cochrane’s RoB 2.0, the Newcastle-Ottawa scale and the ROBINS-IΙ tool. The Synthesis Without Meta-analysis (SWiM) extension was used to present the results. Eight studies were identified delivering interventions with ketogenic diets, intermittent fasting, time-restricted feeding, etc. KDIs were generally associated with weight loss and a more favorable anthropometric profile in most interventions (nine). Blood pressure remained unchanged in most interventions (five), similar to cholesterol, HDL-cholesterol, triglycerides and LDL. Regarding renal outcomes, eGFR was either higher post-intervention (4 interventions) or remained stable post-intervention. htTKV remained unchanged in most of the studies. Evidence for renal structural change was inconsistent and limited by short intervention duration and small sample sizes. The evidence on KDIs for ADPKD is still limited. However, KDIs, particularly caloric-restriction diets, appear promising tools for managing ADPKD. Current human data support metabolic feasibility more consistently than renal disease modification. Renal structural outcomes remain uncertain and longer trials with appropriate comparators, namely the standard of care diet for ADPKD, are needed before KDIs can be recommended routinely for ADPKD. • Ketogenic interventions can reduce body weight and improve the anthropometric profile of patients. • Blood pressure remains, total cholesterol, HDL- and LDL-cholesterol, and triglycerides levels remain unaffected. Concerning renal outcomes, eGFR is either improved or remains stable post-intervention. htTKV also remains unchanged. • Ketogenic interventions are feasible for ADPKD, however, research is still limited. More research is required in order to understand the potential of ketogenic diets to act as an adjuvant treatment for ADPKD.