This study was presented at the World Congress of Nephrology, WCN’26, YOKOHAMA, JAPAN

Introduction

Recent research has revealed that metabolic abnormalities constitute the primary pathological feature of autosomal dominant polycystic kidney disease (ADPKD). Among novel therapeutic strategies, the ketogenic diet has garnered attention for demonstrating efficacy in both renal and hepatic cysts. We are conducting the first clinical study in Asia to evaluate the efficacy and tolerability of a ketogenic diet combined with β-hydroxybutyrate (BHB) and citrate supplementation. Here, we report interim results of 10 patients as a the first part of a larger ongoing study.

Methods

Ten ADPKD patients (Mayo class ≥ C; 4 males and 6 females; median age 46 years) were enrolled. Median baseline eGFR was 56 mL/min/1.73 m2, median htTKV 520 mL/m2, and median htTLV 1,030 mL/m2. Participants followed our institutional ketogenic diet protocol emphasizing adequate hydration and prevention of stone formation, incorporating the medical food KetoCitra (containing BHB and alkaline citrate) to enhance efficacy while minimizing side effects.

MRI-based TKV and TLV were assessed at baseline, 3 months, and 12 months. Primary outcomes were 12-month percentage changes in TKV,TLV and eGFR slope (0–12 M, linear regression). Laboratory parameters (e.g., ketone bodies, uric acid, FIB-4 index) and body composition (weight, fat, muscle mass) were analyzed. Correlations were evaluated by Spearman’s test and multivariable regression adjusting for baseline volume and continuation period (3 M vs 12 M).

Results

Median TKV and TLV changes were −3.0 % −5.1 %, respectively, and the eGFR slope was −5.2 mL/min/1.73 m2/year. Mean ketone level at 3 months showed a significant negative correlation with both TKV and TLV changes (Spearman’s ρ = −0.66, p = 0.037), indicating that higher ketone levels were associated with attenuation of organ volume expansion. Fat reduction showed a parallel trend but was not an independent determinant. These associations remained directionally consistent after adjustment for baseline TKV/TLV and continuation period.

Conclusion

In this 10-patient interim analyze is, early elevation of ketone levels was associated with stabilization of kidney and liver volumes, in parallel with fat reduction. Although exploratory, these findings suggest a potential metabolic mechanism for organ-volume stabilization under ketogenic intervention in ADPKD. This trial is continuing with a total enrollment goal of 200 including a control group to verify these findings.