Kidney Function Trajectories with Tolvaptan in ADPKD Patients with CKD-G5.

Introduction: Improvement of estimated glomerular filtration rate (eGFR) slope has been established using tolvaptan in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). In Japan, the therapeutic dose of tolvaptan (60-120 mg/d) must be discontinued at chronic kidney disease stage G5 (CKD-G5), eGFR < 15 ml/min per 1.73 m. However, low-dose tolvaptan (≤ 15 mg/d) can be continued in CKD-G5 patients with heart failure complicated by kidney failure.

Methods: This was a Japanese nation-wide, multicenter, retrospective observational study. Between May 2014 and September 2019, 110 patients with ADPKD developed CKD-G5 were included (data: previous 10 years). Participants were categorized into 3 groups: the tolvaptan continued group (received tolvaptan before CKD-G5 and reduced the dose to ≤ 15 mg at CKD-G5, = 14), the tolvaptan discontinued group (received tolvaptan before CKD-G5 but discontinued at CKD-G5, = 13), and the non-tolvaptan group (never received tolvaptan, = 83).

Results: The eGFR slope remained stable before and during CKD-G5 in the non-tolvaptan group. In the tolvaptan discontinued group, the eGFR slope was accelerated from before (-3.3 [-4.3, -2.5] ml/min per 1.73 m/yr) to during CKD-G5 (-5.3 [-6.7, -3.8]). However, in the tolvaptan continued group, the eGFR slope did not change from before (-3.9 [-5.4, -2.6]) to during CKD-G5 (-3.8 [-5.4, -3.4]). Compared with the tolvaptan continued group, the eGFR slope worsened significantly from before to during CKD-G5 in the tolvaptan discontinued group ( = .006).

Conclusion: Continuation of low-dose tolvaptan may be effective in suppressing kidney function deterioration in ADPKD patients with CKD-G5. A clinical trial is needed to evaluate its efficacy and safety.