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Abstract: TH-PO425

Eight Years of Canadian Real-World Assessment of Tolvaptan in ADPKD: C-MAJOR Study and Safety Monitoring and Distribution Program

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic


  • McFarlane, Philip, University of Toronto, Toronto, Ontario, Canada
  • Bichet, Daniel G., Universite de Montreal, Montreal, Quebec, Canada
  • Alam, Ahsan, McGill University Faculty of Medicine and Health Sciences, Montreal, Quebec, Canada
  • Bergeron, Luc, Otsuka Canada Pharmaceutical Inc, Saint Laurent, Quebec, Canada
  • Boutin, Sylvie, Otsuka Canada Pharmaceutical Inc, Saint Laurent, Quebec, Canada
  • Laplante, Annick, Otsuka Canada Pharmaceutical Inc, Saint Laurent, Quebec, Canada

Tolvaptan is approved in Canada for slowing renal function decline and kidney enlargement in patient with ADPKD. As required by Health Canada, a patient registry study evaluating long-term clinical outcomes (C-MAJOR) and a hepatic safety monitoring and distribution program (HSMDP) to mitigate risk of liver injury were implemented. The aim of this interim analysis is to describe patient characteristics at tolvaptan initiation from the C-MAJOR study and to report on liver transaminase elevation rates and treatment persistence through the HSMDP.


C-MAJOR is a non-interventional, observational, multi-centre study of ADPKD patients treated with tolvaptan. HSMDP ensures tolvaptan is dispensed under controlled liver function monitoring.


As of February 2023, 469 patients were enrolled in C-MAJOR. At baseline, 51% were female, with a mean (SD) age of 45 (12) years, BP 129 (13)/83 (10) mmHg and eGFR 64 (28) mL/min/1.73 m2. Overall, 68% were in early CKD stages 1, 2 and 3a. Total kidney volume was 1963 (1538) mL, 80% had a family history of ADPKD, 38% had a family history of early end-stage kidney disease, and 91% were at high risk of disease progression (Mayo Imaging Class 1C-D-E). The most common clinical manifestations were hypertension (84%), hepatic cysts (71%) and kidney pain (24%).
From the HSMDP, 82 (3.4%) of the 2418 patients who initiated tolvaptan reported an elevation of transaminases (>3x ULN), with 11 (0.45%) meeting guidelines for permanent discontinuation. No cases of drug-induced liver injury were reported. Occurrence of ALT/AST levels greater than 3x ULN were seen up to 81 months post tolvaptan initiation and of these, 32% of the episodes occurred following the first 18 months of treatment. Treatment persistence rates at 12, 24 and 36 months were 84%, 77% and 72%, respectively.


This analysis provides Canadian real-world evidence that most ADPKD patients treated with tolvaptan are at high-risk of disease progression and three-year treatment persistence is similar to phase III study data. The HSMDP in Canada has been effective at avoiding the incidence of drug-induced liver injury associated with tolvaptan.


  • Commercial Support – Otsuka Canada