The Effect of Tolvaptan on BP in Polycystic Kidney Disease: A Post Hoc Analysis of the TEMPO 3:4 Trial

J Am Soc Nephrol. 2021 Apr 22;32(7):1801-1812. doi: 10.1681/ASN.2020101512. Online ahead of print.

Abstract

Background: The V2 receptor antagonist tolvaptan is prescribed to patients with autosomal dominant polycystic kidney disease to slow disease progression. Tolvaptan may alter BP via various acute and chronic effects.

Methods: To investigate the magnitude and time course of the effect of tolvaptan use on BP, we conducted a post hoc study of the TEMPO 3:4 trial, which included 1445 patients with autosomal dominant polycystic kidney disease randomized 2:1 to tolvaptan or placebo for 3 years. We evaluated systolic and diastolic BP, mean arterial pressure, hypertension status, and use and dosing of antihypertensive drugs over the course of the trial.

Results: At baseline, BP did not differ between study arms. After 3 weeks of tolvaptan use, mean body weight had decreased from 79.7 to 78.8 kg, and mean plasma sodium increased from 140.4 to 142.6 mmol/L (both P<0.001), suggesting a decrease in circulating volume. We observed none of these changes in the placebo arm. Nonetheless, BP remained similar in the study arms. After 3 years of treatment, however, mean systolic BP was significantly lower in participants receiving tolvaptan versus placebo (126 versus 129 mm Hg, respectively; P=0.002), as was mean diastolic BP (81.2 versus 82.6 mm Hg, respectively; P=0.01). These differences leveled off at follow-up 3 weeks after discontinuation of the study medication. Use of antihypertensive drugs remained similar in both study arms during the entire study.

Conclusions: Long-term treatment with tolvaptan gradually lowered BP compared with placebo, which may be attributed to a beneficial effect on disease progression, a continued natriuretic effect, or both.

Clinical trial registry name and registration number: TEMPO 3:4, NCT00428948.

Keywords: ADPKD; V2 receptor antagonist; blood pressure; vasopressin.

Associated data

  • ClinicalTrials.gov/NCT00428948