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

BACKGROUND

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

METHODS

To investigate the magnitude and time course of the effect of tolvaptan use on BP, we conducted a 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 <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; =0.002), as was mean diastolic BP (81.2 versus 82.6 mm Hg, respectively; =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.