MO031: Long-term safety of treatment with tolvaptan in patients with autosomal dominant polycystic kidney disease

Abstract

Abstract BACKGROUND AND AIMS Tolvaptan, a vasopressin antagonist, is a drug that acts by slowing the progression of autosomal dominant polycystic kidney disease (ADPKD). Its administration is not free of side effects. To assess the long-term safety profile of ADPKD patients treated with tolvaptan. METHOD Retrospective observational study was undertaken of ADPKD patients on treatment with tolvaptan. RESULTS Of the 182 ADPKD patients under follow-up in our hospital, 18% (n = 33) started treatment. Of these, 60.6% (n = 20) were male, with an age of 47.64 ± 8.64 years, a baseline Fg of 65.24 ± 20.14 mL/min, TKVh of 1137.45 ± 667.58 mL and a mean follow-up time of 39.85 ± 10.04 months. A total of 72.7% reached the maximum dose (120 mg), the mean maximum dose reached being 108.18 ± 22.42 mg. At the time of the study, 100% of the patients had reached the maximum dose, the mean time to reach it being 5.8 ± 9.3 weeks. A total of 90.9% (n = 30) presented with side effects: 81.8% (n = 27) aquaretic and 12.1% (n = 4) hepatotoxicity. Others being hypernatremia in 9.1% (n = 3) and hyperuricemia in 24% (n = 8). No other side effects were described. A total of 39.4% (n = 13) of the patients temporarily discontinued treatment after 3.01 ± 2.17 months. The reasons were as follows: aquaretic effects 35.7% (n = 5), hepatotoxicity 35.7% (n = 5), 3.03% desire for pregnancy (n = 1), 3.03% cerebral hemorrhage (n = 1) and 3.03% (n = 1) worsening of renal function. Some 30.76% (n = 4) of the patients restarted treatment at 5.5 ± 6.76 months. Therefore, the treatment discontinuation rate was 27.2%. The profile of patients with side effects were mostly male (60%) with mean age of 46 ± 8.65 years and TKVh of 1829.93 ± 1172.83 mL .The maximum dose reached in these patients was 107 ± 23.2 mg with a mean time to reach it of 6.19 ± 9.7 ± weeks. Patients who had more aquaretic side effects were characterized by better baseline prior to renal function and a greater decrease in GFR throughout follow-up. No differences in TRV variations were observed. CONCLUSION Tolvaptan treatment is shown to be safe in the long term. However the patient profile to receive treatment must be considered given that a high percentage present aquaretic effects. Regarding hepatotoxicity, although it is another potentially serious effect to consider, it is easily managed and reversible in our studied sample.