Long-term effectiveness and safety of tolvaptan in autosomal dominant polycystic kidney disease

Background and objectives

Evidence on the long-term use of tolvaptan in autosomal dominant polycystic kidney disease (ADPKD) is limited. The aim was to evaluate the tolvaptan effectiveness and safety in real clinical setting.

Material and methods

A single-center observational study (2016–2022) involving ADPKD patients treated with tolvaptan was conducted. Annual change in serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) before and after treatment initiation were evaluated. Change in total kidney volume (TKV), blood pressure (BP) and urinary albuminuria at 12, 24 and 36 months after initiation were also determined. Adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 were analyzed.

Results

A total of 22 patients were included. No significant differences pre- vs post tolvaptan treatment in annual rate of change in eGFR (−3.52 ml/min/1.73 m² [−4.98%] vs −3.98 ml/min/1.73 m² [−8.48%], p = 0.121) and sCr (+0.06 mg/dL [4.22%] vs +0.15 mg/dL [7.77%], p = 0.429) were observed. Tolvaptan improved urinary osmolality at 12 (p = 0.019) and 24 months (p = 0.008), but not at 36 months (p = 0.11). There were no changes in TKV, BP control and urinary albuminuria at 12, 24 or 36 months. A worse response was shown in patients with rapid kidney function decline (p = 0.042). A 36.4% of the patients developed grade III/IV AEs. A 22.7% discontinued treatment due to unacceptable toxicity.

Conclusions

This study shows a modest benefit of tolvaptan in ADPKD patients, as well as safety concerns.