Nutritional considerations for designing ketogenic dietary interventions for people with Autosomal Dominant...

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive genetic disease with few effective treatments available to slow the decline in kidney function. In ADPKD, there has been increasing interest in ketogenic diets, largely based on experimental data showing favorable effects on cyst growth and kidney function. High-quality clinical trials of sufficient duration using clinically relevant endpoints (estimated glomerular filtration rate [eGFR], kidney volume) are crucial to establish efficacy and safety in ADPKD. Although extensive reviews have been published about potential mechanisms of ketogenic diets to slow ADPKD progression, there is no guidance on how these diets should be designed to align with the unique clinical and nutritional needs of people with ADPKD. Potential safety and feasibility concerns for ketogenic diets (risk for nephrolithiasis and cardiovascular disease) should be evaluated in clinical trials to determine whether adherence to a complex diet can be sustained over years. Prior to embarking on a clinical trial, careful development of an ADPKD-appropriate ketogenic diet is required to mitigate against these risks. Thus, the aim of this narrative review is to provide a framework for the specific nutritional factors that should be considered when developing and designing a ketogenic dietary intervention in future clinical trials involving ADPKD patients.