Halting cyst progression in ADPKD using long-term ketogenic metabolic therapy and supplementation with exogenous ketones and alkaline citrate-a case series.

ADPKD is a progressive cystic disorder characterized by increasing total kidney volume (TKV), declining kidney function, and limited disease-modifying options. Emerging preclinical and clinical evidence suggests metabolic interventions may influence cyst growth, but longitudinal imaging data in humans remain limited. We conducted a retrospective case series of four self-referred individuals (ages 33-71) with genetically confirmed truncating PKD1 variants who independently implemented metabolic interventions of varying duration and intensity, including carbohydrate restriction, intermittent fasting, and supplementation with a ketone- and citrate-based medical food (KetoCitra®). Intervention periods ranged from 6 months to approximately 4 years and followed prior phases of documented kidney volume enlargement. Serial abdominal imaging obtained during routine clinical care was re-analyzed using standardized volumetric software to assess TKV, liver volume, and Mayo imaging classification trajectories. Across all four cases, stabilization or reduction in TKV relative to prior growth trends was observed during intervention periods, accompanied by preserved kidney function. One participant transitioned from Mayo Class 1C to 1B, while the remaining three demonstrated downward shifts in Mayo imaging trajectory within their existing classifications. Reductions or attenuated increases in liver volume were also observed in cases with polycystic liver disease. Interventions were reported to be feasible and well tolerated, with no serious adverse events. These observations align with emerging preclinical and clinical evidence suggesting metabolic interventions may attenuate TKV progression in ADPKD. While limited by sample size and intervention heterogeneity, this case series provides hypothesis-generating data to inform prospective controlled trials.