Judith E Heida1, Ron T Gansevoort2, Vicente E Torres3, Olivier Devuyst4,5, Ronald D Perrone6, Jennifer Lee7, Hui Li7, John Ouyang7, Arlene B Chapman8. 1. Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 2. Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands r.t.gansevoort@umcg.nl. 3. Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota. 4. Institute of Physiology, University of Zurich, Zurich, Switzerland. 5. Division of Nephrology, Université Catholique de Louvain, Brussels, Belgium. 6. Division of Nephrology, Department of Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts. 7. Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland. 8. Section of Nephrology, University of Chicago, Chicago, Illinois.
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.
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.
Authors: Ron T Gansevoort; Maatje D A van Gastel; Arlene B Chapman; Jaime D Blais; Frank S Czerwiec; Eiji Higashihara; Jennifer Lee; John Ouyang; Ronald D Perrone; Katrin Stade; Vicente E Torres; Olivier Devuyst Journal: Kidney Int Date: 2019-03-09 Impact factor: 10.612
Authors: María V Irazabal; Laureano J Rangel; Eric J Bergstralh; Sara L Osborn; Amber J Harmon; Jamie L Sundsbak; Kyongtae T Bae; Arlene B Chapman; Jared J Grantham; Michal Mrug; Marie C Hogan; Ziad M El-Zoghby; Peter C Harris; Bradley J Erickson; Bernard F King; Vicente E Torres Journal: J Am Soc Nephrol Date: 2014-06-05 Impact factor: 10.121
Authors: Vicente E Torres; Arlene B Chapman; Olivier Devuyst; Ron T Gansevoort; Ronald D Perrone; Gary Koch; John Ouyang; Robert D McQuade; Jaime D Blais; Frank S Czerwiec; Olga Sergeyeva Journal: N Engl J Med Date: 2017-11-04 Impact factor: 91.245
Authors: Javier Naranjo; Francisco Borrego; José Luis Rocha; Mercedes Salgueira; Maria Adoración Martín-Gomez; Cristhian Orellana; Ana Morales; Fernando Vallejo; Pilar Hidalgo; Francisca Rodríguez; Remedios Garófano; Isabel González; Rafael Esteban; Mario Espinosa Journal: Front Med (Lausanne) Date: 2022-09-29