Abstract: PO1543
The Effect of Trichlormethiazide in Patients with Autosomal Dominant Polycystic Kidney Disease Using Tolvaptan: A Randomized Cross-Over Controlled Trial
Session Information
- Cystic Kidney Diseases: Mechanisms, Genetics, and Treatment
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1001 Genetic Diseases of the Kidneys: Cystic
Authors
- Uchiyama, Kiyotaka, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
- Ishibashi, Yoshitaka, Japanese Red Cross Medical Center, Shibuya-ku, Tokyo, Japan
Background
The vasopressin V2 receptor antagonist tolvaptan has been shown to slow the progression of autosomal dominant polycystic kidney disease (ADPKD). However, some patients discontinue tolvaptan due to severe adverse aquaretic events. This open-label, randomized, controlled, counterbalanced, crossover trial investigated the effects of trichloromethiazide, a thiazide diuretic, on reducing urinary volume and improving tolvaptan tolerability in patients with ADPKD on high-dose tolvaptan, based on the effects of thiazides in patients with nephrogenic diabetes insipidus.
Methods
A total of 10 patients with ADPKD on high-dose tolvaptan (median age, 49 years; 4 males) received antihypertensive therapy with or without trichloromethiazide in random order for 12 weeks. The starting doses for trichloromethiazide were 2 and 4 mg in patients with estimated glomerular filtration rates of ≥30 and <30 mL/min/1.73 m2, respectively. Target blood pressure range was 110/70–130/80 during the study period. Primary outcomes were 24-h urine volume and urine osmolarity. Secondary outcomes were health-related quality of life (HRQOL) assessed by the Kidney Disease Quality of Life-Short Form questionnaire, rate of decline in renal function, serum/urinary electrolytes, serum/urinary biomarkers associated with chronic kidney disease and ADPKD progression, and office blood pressure.
Results
The urine volume was significantly reduced (3324 ± 614 vs. 4169 ± 729 mL; P < 0.001) along with an increase in urinary osmolarity (179.0 ± 26.6 vs. 139.1 ± 39.6 mOsm; P = 0.001) in patients on antihypertensive therapy with trichloromethiazide. Moreover, trichloromethiazide improved several HRQOL subscales including effects of kidney disease, sleep, emotional role functioning, social functioning, and role/social component summary. There were no significant differences in the slope of estimated glomerular filtration rate assessed by creatinine and cystatin C or serum/urinary biomarkers between the patients on antihypertensive therapy with and without trichloromethiazide. Office blood pressure was not significantly different between the treatment groups.
Conclusion
In patients with ADPKD treated with high-dose tolvaptan, trichloromethiazide may improve tolvaptan tolerability and HRQOL by reducing urinary volume without affecting ADPKD-related parameters.