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


Heida, Judith E; Gansevoort, Ron T; Torres, Vicente E; Devuyst, Olivier; Perrone, Ronald D; Lee, Jennifer; Li, Hui; Ouyang, John; Chapman, Arlene B (2021). The Effect of Tolvaptan on BP in Polycystic Kidney Disease: A Post Hoc Analysis of the TEMPO 3:4 Trial. Journal of the American Society of Nephrology (JASN), 32(7):1801-1812.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Nephrology
Uncontrolled Keywords:Nephrology, General Medicine
Language:English
Date:1 July 2021
Deposited On:13 Sep 2021 14:57
Last Modified:14 Sep 2021 20:00
Publisher:American Society of Nephrology
ISSN:1046-6673
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1681/asn.2020101512
PubMed ID:33888577
Project Information:
  • : FunderOtsuka Pharmaceutical
  • : Grant ID
  • : Project Title
  • : FunderBRAHMS GmbH, Henningsdorf, Germany
  • : Grant ID
  • : Project Title

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