PURPOSE:Tolvaptan, a vasopressin V2 receptor antagonist, slows the decline in renal function in autosomal dominant polycystic kidney disease (ADPKD). However, it increases urine output such that patient adherence could be compromised. In a cohort of patients with ADPKD on tolvaptan, we aimed to identify the contribution of sodium and urea excretion rate to daily urine output, and to evaluate the effectiveness of dietary counseling on sodium and urea excretion rates. METHODS:Retrospective analysis of 30 ADPKD patients who underwent a single session of personalized dietary counseling to reduce sodium and protein intake before initiation of tolvaptan. Creatinine and 24-h urine were obtained regularly on treatment. Generalized estimation equations were used. RESULTS:Mean age and median eGFR were 44 ± 11 years and 52 (43-74) ml/min/1.73 m2. Tolvaptan increased diuresis from 2.5 to 5.2 l/day. After adjusting for the dose of tolvaptan, an increase in sodium and urea excretion rate by 50 mmol/day was associated with an estimated additional urine volume of 0.6 l/day (95% CI 0.4-0.8 l/day; P < 0.001) and 0.25 l/day (95% CI 0.11-0.39 l/day; P < 0.001), respectively. Dietary counseling resulted in a transient reduction of sodium excretion by 19 mmol/day during the first 4 months (P = 0.016) but resulted in a more sustained reduction in urea excretion by 69 mmol/day (P = 0.008). CONCLUSION:Both sodium and urea excretion rates contribute significantly to daily urine volume in patients treated with tolvaptan, and a single session of dietary counseling was transiently effective in reducing sodium intake but achieved a more sustained reduction in protein intake. Dietary counseling should be considered in the management of ADPKD patients treated by tolvaptan.