Abstract
The vasopressin V2 receptor antagonist tolvaptan delays the progression of autosomal dominant polycystic kidney disease (ADPKD). However, some patients discontinue tolvaptan because of severe adverse aquaretic events. This open-label, randomized, controlled, counterbalanced, crossover trial investigated the effects of trichlormethiazide, a thiazide diuretic, in patients with ADPKD receiving tolvaptan (n = 10) who randomly received antihypertensive therapy with or without trichlormethiazide for 12 weeks. The primary and secondary outcomes included amount and osmolarity of 24-h urine and health-related quality-of-life (HRQOL) parameters assessed by the Kidney Disease Quality of Life-Short Form questionnaire, renal function slope, and plasma/urinary biomarkers associated with disease progression. There was a significant reduction in urine volume (3348 ± 584 vs. 4255 ± 739 mL; P < 0.001) and a significant increase in urinary osmolarity (182.5 ± 38.1 vs. 141.5 ± 38.1 mOsm; P = 0.001) in patients treated with trichlormethiazide. Moreover, trichlormethiazide improved the following HRQOL subscales: effects of kidney disease, sleep, emotional role functioning, social functioning, and role/social component summary. No significant differences were noted in renal function slope or plasma/urinary biomarkers between patients treated with and without trichlormethiazide. In patients with ADPKD treated with tolvaptan, trichlormethiazide may improve tolvaptan tolerability and HRQOL parameters.
Highlights
The vasopressin V2 receptor antagonist tolvaptan delays the progression of autosomal dominant polycystic kidney disease (ADPKD)
The vasopressin V2 receptor antagonist tolvaptan has been recently shown to delay the increase in total kidney volume (TKV) as well as decline in kidney functions compared with placebo in a randomized controlled trial (RCT) of patients with ADPKD with near-normal kidney functions and late-stage A DPKD2,3
The present study is the first pilot RCT to describe the effect of trichlormethiazide, a thiazide diuretic, on reducing urinary volume while increasing urinary osmolarity (Uosm) in patients with ADPKD receiving high-dose tolvaptan
Summary
The vasopressin V2 receptor antagonist tolvaptan delays the progression of autosomal dominant polycystic kidney disease (ADPKD). Some patients discontinue tolvaptan because of severe adverse aquaretic events This open-label, randomized, controlled, counterbalanced, crossover trial investigated the effects of trichlormethiazide, a thiazide diuretic, in patients with ADPKD receiving tolvaptan (n = 10) who randomly received antihypertensive therapy with or without trichlormethiazide for 12 weeks. The primary and secondary outcomes included amount and osmolarity of 24-h urine and health-related quality-of-life (HRQOL) parameters assessed by the Kidney Disease Quality of Life-Short Form questionnaire, renal function slope, and plasma/urinary biomarkers associated with disease progression. We designed an open-label, pilot, randomized, controlled, crossover trial involving patients with ADPKD receiving tolvaptan to primarily clarify the effect of trichlormethiazide, the most popular thiazide agent in Japan, in improving tolvaptan tolerability as well as to assess its impact on health-related quality-of-life (HRQOL) parameters of patients as one of the secondary endpoints. As the case report indicated that thiazide deteriorates the effect of tolvaptan on the rate of ADPKD progression, we evaluated the short-term effects of trichlormethiazide on renal function and plasma/urinary biomarkers
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