Long-term administration of tolvaptan in autosomal dominant polycystic kidney disease

Marie E. Edwards, Fouad T. Chebib, Maria V. Irazabal, Troy G. Ofstie, Lisa A. Bungum, Andrew J. Metzger, Sarah R. Senum, Marie C. Hogan, Ziad M. El-Zoghby, Timothy L. Kline, Peter C. Harris, Frank S. Czerwiec, Vicente E. Torres

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Background and objectives In the 3-year Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 and 1-year Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trials, tolvaptan slowed the decline of eGFR in patients with autosomal dominant polycystic kidney disease at early and later stages of CKD, respectively. Our objective was to ascertain whether the reduction associated with the administration of tolvaptan is sustained, cumulative, and likely to delay the need for kidney replacement therapy. Design, setting, participants, & measurements One hundred and twenty-eight patients with autosomal dominant polycystic kidney disease participated in clinical trials of tolvaptan at the Mayo Clinic. All had the opportunity to enroll into open-label extension studies. Twenty participated in short-term studies or received placebo only. The remaining 108 were analyzed for safety. Ninety seven patients treated with tolvaptan for ≥1 year (mean±SD, 4.662.8; range, 1.1–11.2) were analyzed for efficacy using three approaches: (1) comparison of eGFR slopes and outcome (33% reduction from baseline eGFR) to controls matched by sex, age, and baseline eGFR; (2) Stability of eGFR slopes with duration of follow-up; and (3) comparison of observed and predicted eGFRs at last follow-up. Results Patients treated with tolvaptan had lower eGFR slopes from baseline (mean±SD,–2.20±2.18ml/min per 1.73m 2 per year) and from month 1 (mean±SD,–1.97±2.44 ml/min per 1.73m 2 per year) compared with controls (mean±SD, 23.50±2.09 ml/min per 1.73 m 2 per year; P<0.001), and lower risk of a 33% reduction in eGFR (risk ratio, 0.63; 95%confidence interval, 0.38 to 0.98 from baseline; risk ratio, 0.53; 95%confidence interval, 0.31 to 0.85 from month 1). Annualized eGFR slopes of patients treated with tolvaptan did not change during follow-up and differences between observed and predicted eGFRs at last follow-up increased with duration of treatment. Conclusions Follow-up for up to 11.2 years (average 4.6 years) showed a sustained reduction in the annual rate of eGFR decline in patients treated with tolvaptan compared with controls and an increasing separation of eGFR values over time between the two groups.

Original languageEnglish (US)
Pages (from-to)1153-1161
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Issue number8
StatePublished - Aug 7 2018


  • Benzazepines
  • Chronic kidney disease
  • EGFR protein, human
  • Follow-Up Studies
  • Glomerular filtration rate
  • Humans
  • Polycystic Kidney, Autosomal Dominant
  • Polycystic kidney disease
  • Receptor, Epidermal Growth Factor
  • Renal Insufficiency, Chronic
  • Renal Replacement Therapy
  • Tolvaptan
  • Vasopressin
  • Vasopressin Receptor Antagonist

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation


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