and lifestyle interventions Research using ADPKD mouse models showed that mild food restriction strongly improved disease progression. The mechanism was shown to involve the metabolic state of ketosis, and beneficial effects could be produced by time-restricted feeding, acute fasting, a ketogenic diet, or by supplementation with the ketone beta-hydroxybutyrate in mouse, rat and cat models of ADPKD. A ketogenic diet regimen not only halted further disease progression but led to partial reversal of renal cystic disease in a rat model. The metabolic state of ketosis may be beneficial in ADPKD because renal cyst cells in ADPKD have a metabolic defect similar to the Warburg effect in cancer that makes them highly dependent on glucose, and unable to metabolize fatty acids and ketones. Consistent with this, serum glucose levels positively correlate with faster disease progression in ADPKD patients. Also, individuals with ADPKD and type 2 diabetes have significantly larger total kidney volume (TKV) than those with ADPKD alone, and overweight or obesity associate with faster progression in early-stage ADPKD. A retrospective case series study showed that ADPKD disease symptoms - including pain, hypertension and renal function - improved among 131 patients who implemented ketogenic diets for an average duration of 6 months. Dietary intake of sodium is associated with worse renal function decline in ADPKD, and limiting sodium intake is generally recommended to patients. Dietary protein intake was not found to correlate with ADPKD progression. Increased water intake is thought to be beneficial in ADPKD and is generally recommended. The underlying beneficial mechanism of increased water intake may be related to effects on the vasopressin V2 receptor or may be due to the suppression of harmful micro-crystal formation in renal tubules by dilution of solutes such as calcium oxalate, calcium phosphate and uric acid. Dietary intake of oxalate or inorganic phosphate has been shown to accelerate PKD disease progression in several rodent models. Low levels or urinary citrate – a natural antagonist of the formation of harmful crystals in kidney tubules – have been shown to associate with worse disease progression in ADPKD patients. Analgesic medication Chronic pain in patients with ADPKD is often refractory to conservative, noninvasive treatments, but nonopioid analgesics and conservative interventions can be first used before opioid analgesics are considered; if pain continues, then surgical interventions can target renal or hepatic cysts to directly address the cause of pain, with surgical options including renal cyst decortication, renal