Albuminuria and tolvaptan in autosomal-dominant polycystic kidney disease: Results of the TEMPO 3:4 Trial

Ron T. Gansevoort, Esther Meijer, Arlene B. Chapman, Frank S. Czerwiec, Olivier Devuyst, Jared J. Grantham, Eiji Higashihara, Holly B. Krasa, John Ouyang, Ronald D. Perrone, Vicente E. Torres

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

BackgroundThe TEMPO 3:4 Trial results suggested that tolvaptan had no effect compared with placebo on albuminuria in autosomal-dominant polycystic kidney disease (ADPKD) patients. However, the use of categorical 'albuminuria events' may have resulted in a loss of sensitivity to detect changes. The aim of this study is to investigate the effects of tolvaptan on albuminuria as a continuous variable. MethodsPost hoc analysis of a 3-year prospective, blinded randomized controlled trial, including 1375 ADPKD patients. Albuminuria was measured in a spot morning urine sample prior to tolvaptan dosing and expressed as albumin-to-creatinine ratio (ACR). ResultsBaseline median (interquartile range) ACR was 3.2 (1.7-7.1) mg/mmol. Of note, 47.9% of ADPKD patients had normal, 48.7% moderately increased and 3.4% severely increased ACR. Subjects with higher baseline ACR had higher blood pressure and total kidney volume (TKV) and lower estimated glomerular filtration rate (eGFR). During follow-up, higher baseline ACR was associated with more rapid eGFR loss (P < 0.0001 for trend), but not with rate of growth in TKV. During the 3-year trial, ACR rose in placebo- and decreased in tolvaptan-treated patients (+0.23 versus -0.40 mg/mmol). The difference ACR increased over time, reaching a maximum of 24% at Month 36 (P < 0.001). At that time only a minor difference in blood pressure was observed (mean arterial pressure -1.9 mmHg for tolvaptan). The decrease in ACR was similar in all subgroups investigated, and remained after withdrawal of study drug. The beneficial effect of tolvaptan on TKV growth and eGFR loss was stronger in patients with higher baseline ACR. ConclusionsIn ADPKD, higher baseline albuminuria was associated with more eGFR loss. Tolvaptan decreased albuminuria compared with placebo, independent of blood pressure. Treatment efficacy of tolvaptan on changes in TKV and eGFR was more readily detected in patients with higher albuminuria.

Original languageEnglish (US)
Pages (from-to)1887-1894
Number of pages8
JournalNephrology Dialysis Transplantation
Volume31
Issue number11
DOIs
StatePublished - Nov 1 2016

Keywords

  • ADPKD
  • albuminuria
  • chronic renal failure
  • eGFR
  • vasopressin

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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