The effect of trichlormethiazide in autosomal dominant polycystic kidney disease patients receiving tolvaptan: a randomized crossover controlled trial

Sci Rep. 2021 Sep 3;11(1):17666. doi: 10.1038/s41598-021-97113-w.

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antidiuretic Hormone Receptor Antagonists / therapeutic use*
  • Cross-Over Studies
  • Drug Therapy, Combination
  • Female
  • Humans
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Polycystic Kidney, Autosomal Dominant / drug therapy*
  • Polycystic Kidney, Autosomal Dominant / physiopathology
  • Quality of Life
  • Sodium Chloride Symporter Inhibitors / therapeutic use*
  • Tolvaptan / therapeutic use*
  • Treatment Outcome
  • Trichlormethiazide / therapeutic use*

Substances

  • Antidiuretic Hormone Receptor Antagonists
  • Sodium Chloride Symporter Inhibitors
  • Tolvaptan
  • Trichlormethiazide