Abstract
BACKGROUND: The diuretic effect of tolvaptan, a vasopressin V2 receptor antagonist, in patients with severe renal dysfunction remains poorly characterized. Thiazide diuretics reduce urinary volume (UV) in patients with nephrogenic diabetes insipidus, which lacks V2 receptor function. OBJECTIVE: This retrospective study investigated the acute urinary effects of tolvaptan in patients with stage G5 chronic kidney disease and congestive heart failure (CHF), and the impact of thiazide diuretics on the urinary effects of tolvaptan. METHODS: UVs 24 h before and after tolvaptan administration and 30-day dialysis initiation rate were compared between patients with and without thiazide diuretic administration. RESULTS: Thiazide diuretics were used in 26 of the 106 recruited patients (age 73.4 ± 13.0 years; estimated glomerular filtration rate 8.07 ± 3.13 mL/min/1.73 m(2)). The pre- and post-tolvaptan 24-h UVs were significantly higher in patients not administered thiazide diuretics (1043.4 ± 645.6 vs. 1422.2 ± 774.0 mL/day; p < 0.001) than in those administered thiazide diuretics (1177.3 ± 686.5 vs. 1173.1 ± 629.1 mL/day; p = 0.93). In a multivariate regression model, thiazide diuretic use was significantly associated with decreased 24-h UV (β coefficient - 486.7, 95% confidence interval [CI] - 674.5 to - 298.8); increased urine osmolality (β coefficient 37.7, 95% CI 17.1-58.4); increased body weight (β coefficient 0.62, 95% CI 0.31-0.92); and increased 30-day dialysis initiation rate (odds ratio 3.40, 95% CI 1.18-9.82) after tolvaptan administration. CONCLUSIONS: Tolvaptan exhibited significant diuretic effects in patients with CHF, including those with severe renal dysfunction, which were diminished with concomitant thiazide diuretic use.