Heida Judith E, Gansevoort Ron T, Torres Vicente E, Devuyst Olivier, Perrone Ronald D, Lee Jennifer, Li Hui, Ouyang John, Chapman Arlene B
Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
J Am Soc Nephrol. 2021 Jul;32(7):1801-1812. doi: 10.1681/ASN.2020101512. Epub 2021 Apr 22.
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.
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.
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.
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.
TEMPO 3:4, NCT00428948.
血管加压素2型受体拮抗剂托伐普坦被用于治疗常染色体显性多囊肾病患者，以减缓疾病进展。托伐普坦可能通过各种急性和慢性效应来改变血压。
为了研究托伐普坦对血压影响的程度和时间过程，我们对TEMPO 3:4试验进行了一项研究，该试验纳入了1445例常染色体显性多囊肾病患者，按照2:1的比例随机分为托伐普坦组或安慰剂组，治疗3年。我们在试验过程中评估了收缩压和舒张压、平均动脉压、高血压状态以及降压药物的使用和剂量。
在基线时，研究组之间的血压没有差异。使用托伐普坦3周后，平均体重从79.7千克降至78.8千克，平均血浆钠从140.4毫摩尔/升增至142.6毫摩尔/升（均P<0.001），提示循环血容量减少。在安慰剂组未观察到这些变化。尽管如此，研究组之间的血压仍保持相似。然而，治疗3年后，接受托伐普坦治疗的参与者的平均收缩压显著低于安慰剂组（分别为126毫米汞柱和129毫米汞柱；P=0.002），平均舒张压也是如此（分别为81.2毫米汞柱和82.6毫米汞柱；P=0.01）。在停用研究药物3周后的随访中，这些差异趋于平稳。在整个研究过程中，两个研究组的降压药物使用情况保持相似。
与安慰剂相比，托伐普坦长期治疗可逐渐降低血压，这可能归因于对疾病进展的有益作用、持续的利钠作用或两者兼有。
TEMPO 3:4，NCT00428948。
