Study Design
Retrospective case series of four self-referred individuals (ages 33-71) with genetically confirmed truncating PKD1 variants. All had severe genotypes associated with rapid progression. Intervention periods ranged from 6 months to approximately 4 years. TKV measured via MRI and analyzed with TRACEORG automated segmentation in blinded fashion. Mayo Imaging Classification used to track progression trajectory.
Intervention
Combined metabolic approach: ketogenic diet (<25-50 g carbs/day, ~75% fat), intermittent fasting (16:8 time-restricted feeding), and KetoCitra supplementation (5.3g BHB, 3.5g citrate, 600mg potassium, 300mg calcium, 250mg magnesium, 51 mEq alkaline base per day). Blood BHB >0.5 mmol/L and glucose <100 mg/dL used as markers of nutritional ketosis.
Key Results
TKV Trajectory: Stabilized or reversed in all 4 cases
All participants showed downward shifts in Mayo imaging trajectory. One shifted from Class 1C to 1B. Case 4 reversed from +77 mL/year growth to -47 mL/year reduction.
eGFR: Preserved in all cases
No decline in kidney function. Case 4 (age 71) showed eGFR improvement from 55.3 to 63 mL/min/1.73 m2 over 3 years.
Liver Volume: Reduced in polycystic liver cases
Cases with polycystic liver disease showed liver volume reductions (Case 3: 2,176 to 1,801 mL). Liver growth rate attenuated in Case 4 from +141 to +24 mL/year.
Safety: No serious adverse events
No kidney stones despite elevated risk with keto diets. No metabolic acidosis, electrolyte disturbances, or liver dysfunction. Mild transient keto-flu symptoms reported.
Context & Comparison
Spontaneous downward shifts in TKV are not a known feature of ADPKD. Truncating PKD1 variants are associated with the most severe disease course. These results in high-risk genotypes are consistent with the Juntendo 12-month trial data and the Ren-Nu real-world outcomes, extending the evidence to longer intervention durations (up to 4 years).
Significance
This is the longest-duration published data on ketogenic metabolic therapy in ADPKD, with one participant followed for approximately 4 years. All four individuals — carrying the most severe PKD1 genotype class — demonstrated TKV stabilization or reduction and preserved kidney function. The combination of ketogenic diet, intermittent fasting, and KetoCitra supplementation was feasible and well-tolerated long-term. Results are exploratory and hypothesis-generating, supporting the need for prospective controlled trials.