Kidney Week

Abstract: FR-PO613

Long Term Effect of High Dose Tolvaptan Treatment for Autosomal Dominant Polycystic Kidney Disease Patient

Session Information

• Trainee Case Reports - IV
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Reports

• 1001 Genetic Diseases of the Kidney: Cystic

Authors

• Machiba, Yuri, Osaka City University Graduate School of Medicine, Osaka, Japan

Yuri Machiba,

• Nakatani, Shinya, Osaka City University Graduate School of Medicine, Osaka, Japan

Shinya Nakatani,

• Ishimura, Eiji, Meijibashi Hospital, Matsubara-shi, Osaka-Fu, Japan

Eiji Ishimura,

• Uedono, Hideki, Osaka City University Graduate School of Medicine, Osaka, Japan

Hideki Uedono,

• Nakatani, Ayumi, Osaka City University Graduate School of Medicine, Osaka, Japan

Ayumi Nakatani,

• Tsuda, Akihiro, Osaka City University Graduate School of Medicine, Osaka, Japan

Akihiro Tsuda,

• Mori, Katsuhito, Osaka City University Graduate School of Medicine, Osaka, Japan

Katsuhito Mori,

• Inaba, Masaaki, Osaka City University Graduate School of Medicine, Osaka, Japan

Masaaki Inaba,

Introduction

Based on the results of Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcome (TEMPO) 3:4 trial, tolvaptan was firstly approved by regulatory authority in Japan (March, 2014), as a therapy for Autosomal dominant polycystic kidney disease (ADPKD) patients. However, to date, the long term efficacy and safety of high dose tolvaptan is unknown. Here, we present a Japanese case with ADPKD, who have continued a high dose of tolvaptan (a total daily dose of 120 mg) for 9 years from the beginning of the TEMPO 3:4 trial.

Case Description

A 36-year-old man was diagnosed with ADPKD in 2008. His estimated glomerular filtration rate was 57.3 mL/ min/1.73 m² calculated as Japanese formul, ａｎｄ the total kidney volume (TKV) was 1499 mL.Tolvaptan was started at a dose of 60 mg/day (with 45 mg given in the morning and 15 mg in the evening), with weekly increase by 30mg/day, and finally to 120 mg/day divided into 90 mg in the morning and 30 mg in the evening.The rate of eGFR decline during tolvaptan treatment was - 3.01 mL/min/1.73 m² per year (57.3 mL/ min/1.73 m² before the treatment of tolvaptan; and 34.4 mL/ min/1.73 m² 9 years later). The TKV increased by 6.17 %/year (1499mL before the treatment; and 2328 mL 9years later). During 9-year period, the patient has showed no tolvaptan-related adverse events, such as liver dysfunction, and hypernatremia, which were more common adverse events in tolvaptan group of the TEMPO 3:4 trial⁹. Tolvaptan treatment is continuing in this patient, and his condition is stable now.

Discussion

The post hoc exploratory analysis of the TEMPO3:4 trial also revealed that tolvaptan decrease the rate of eGFR by - 3.70 mL/min/1.73m² /year (n=151, 95% confidential interval:- 4.04 to - 3.36 mL/min/1.73m² /year) in the tolvaptan group and - 5.36 mL/min/1.73m² year (n=84, 95% confidential interval:- 6.19 to - 4.53 mL/min/1.73m² /year) in the placebo group, in ADPKD patients with CKD stage 33. In our patient, during 9-year period, the rate of eGFR decline was -3.01ml/min/1.73 m² /year, which was similar to the results of the previous study. Thus, high dose of tolvaptan treatment for the protection of kidney function could be maintained in longer term, even in patients with CKD stage 3.