Tolvaptan for Treatment of ADPKD in Japan

Results of the TEMPO (Tolvaptan Efficacy and Safety in the Management of ADPKD and its Outcomes) and REPRISE (Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy in ADPKD) trials demonstrated that tolvaptan slows the decline in estimated glomerular filtration rate (eGFR) in patients with autosomal dominant polycystic kidney disease (ADPKD). However, according to Yasuhiro Oda, MD, and colleagues, real-world data on the change in eGFR in patients with ADPKD treated with tolvaptan are lacking. In addition, there are few data comparing the slopes of the change in eGFR prior to and following initiation of tolvaptan.

The researchers conducted a retrospective analysis of patients who initiated tolvaptan between June 2014 and June 2019 at Toranomon Hospital, Tokyo, Japan, and Toranomon Hospital Kajigaya, Kawasaki, Japan. Results of the analysis were reported during a virtual poster session as ASN Kidney Week 2020 in a poster titled Tolvaptan and Renal Function in Autosomal Dominant Polycystic Disease: A Two-Center Experience of 186 Cases.

Approved indication for tolvaptan for ADPKD patients in Japan includes total kidney volume larger than 750 mL and eGFR greater than 15 mL/min/1.73 m2. Medical records were used to determine eGFR at 1, 2, 3, 4, and 5 years before and after initiation of treatment with tolvaptan. Patients with missing values were excluded from the analysis.

A total of 186 patients were included in the study. Of those, 43% were men, and average age was 50.2 years. When stratified by chronic kidney disease (CKD) stage, total kidney volume was: stage 1, 1119 mL; stage 2, 1521 mL; stage 3a, 1659 mL; stage 3b, 2106 mL; and stage 4, 2847 mL. Data on eGFR before and after tolvaptan initiation were available for 139 patients; 24 patients had data only before tolvaptan initiation, and 23 had data only after tolvaptan initiation.

The overall eGFR slope after tolvaptan initiation was –3.7 mL/min/1.73 m2 per year. When stratified by CKD stage, the slope was: stage 1, –5.9 mL/min/1.73 m2 per year (n=162); stage 2, –4.5 mL/min/1.73 m2 per year (n=47); stage 3a, –3.1 mL/min/1.73 m2 per year (n=38); stage 3b, –3.5 mL/min/1.73 m2 (n=40); and stage 4, 3.3 mL/min/1.73 m2 per year (n=33).

The change in eGFR slope following initiation of tolvaptan was –1.2 mL/min/1.73 m2 per year in stage 1-3a patients (n=76) and +0.8 mL/min/1.73 m2 per year in stage 3b-4 patients (n=63), a statistically significant difference (P=.003).

“Real-world data from our institution observed the eGFR slope of –3.7 ±2.3 mL/min/1.73 m2 after starting taking tolvaptan. The eGFR slope in patients with CKD stage 3b-4 improved on average,” the researchers said.

Source: Oda Y, Ikuma D, Mizuno H, et al. Tolvaptan and renal function in autosomal dominant polycystic disease: A two-center experience of 186 cases. Abstract of a poster presented at the American Society of Nephrology virtual Kidney Week 2020 (PO1535), October 22, 2020.