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

Background/objectives: 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, and provide a direction for future research and relevant recommendations. Methods: 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. 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 blood cholesterol, HDL-cholesterol, triglycerides and LDL concentrations. Regarding renal outcomes, eGFR was either higher (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. Conclusions: 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. The effects of KDIs on renal structural outcomes remain uncertain and longer trials with appropriate comparators, namely the standard of care diet for ADPKD, are required before KDIs can be recommended for ADPKD.