Measuring the Impact of tolvaptan-induced polyuria on quality of life in patients with autosomal dominant polycystic kidney disease

Abstract Introduction Tolvaptan, a vasopressin V2 receptor antagonist (V2RA), is the only proven renoprotective therapy for patients with autosomal dominant polycystic kidney disease (ADPKD), but aquaretic side-effects limit its tolerability. Currently, no patient-reported outcome measures (PROMs) specifically assess the impact of tolvaptan on health-related quality of life (HRQoL) in ADPKD. Methods We developed the Tolvaptan Impact of Polyuria Scale (TIPS) questionnaire to evaluate tolvaptan-related treatment burden, with higher scores indicating greater burden. The TIPS, alongside the ADPKD-Urinary Impact Scale (ADPKD-UIS) and Short-Form 12 (SF-12) questionnaires, was administered to 152 participants: 47 healthy controls and repeatedly in 105 patients with ADPKD, including those that were untreated (n = 48), on a stable tolvaptan dose (n = 33), or undergoing tolvaptan dose titration (n = 24). All participants also completed standardized 24-hour urine collections. Results Untreated patients with ADPKD reported a lower HRQoL than healthy controls. Tolvaptan-treated patients had significantly higher 24-hour urine volumes (5139 ± 193 versus 2474±180 ml, p < 0.001), with elevated TIPS total (48.0 ± 3.8 versus 37.3 ± 3.4, p = 0.04) and ADPKD-UIS total scores (19.2 ± 1.0 versus 15.6 ± 0.9, p = 0.01) compared to untreated patients, reflecting treatment burden. Twenty-four hour urine volume correlated with TIPS total (r = 0.56 [95% CI: 0.38, 0.78, p < 0.001]) and ADPKD-UIS total scores (r = 0.71 [95% CI: 0.58, 0.83, p < 0.001]), but not with SF-12 scores. TIPS scores were stable over time in treated- and untreated ADPKD patients. During tolvaptan titration, the greatest changes in 24-hour urine volume and HRQoL occurred at the initial dose (45/15 mg), with significant treatment burden across HRQoL domains. Among patients who discontinued tolvaptan during titration due to aquaretic side effects, unlike the ADPKD-UIS, TIPS scores were higher compared to those who continued treatment, suggesting better differentiation by the TIPS. Conclusion Tolvaptan treatment significantly impacts HRQoL in ADPKD. The TIPS questionnaire effectively captures the physical, mental, and social burden of tolvaptan-induced polyuria, and provides a reliable PROM for clinical care and research.