MO025TREATMENT WITH TOLVAPTAN IN ADPKD PATIENTS: RESULTS FROM AN OBSERVATIONAL, MULTICENTRIC STUDY

Abstract

Abstract Background and Aims In recent years, treatment of ADPKD (Autosomal Dominant Polycystic Kidney of the Adult) has been based on the antisecretive and antiproliferative effect of several drugs. Tolvaptan, a vasopressin receptor antagonist, has been shown to slow disease progression in the face of side effects such as aquaresis and liver damage. Currently, the drug's reimbursability is allowed in patients aged up to 55 years, CKD 2-4 (GFR ≥ 25 ml/min) with evidence of rapid disease progression. Method We report the experience with Tolvaptan in 62 patients with ADPKD who were recruited from 11 Nephrology Units in Lazio (Italy). Baseline characteristics of patients are reported in Table 1. Renal volume was evaluated by MRI (26 patients), CT scan (3 patients), or ultrasonography (28 patients). Rapid progression’s criteria were the following: Mayo Clinic classification, PRO-PKD score and the annual loss of GFR. Mean duration of Tolvaptan’s treatment was 522 days (range 56-867). The Tolvaptan dosage used at the beginning of therapy was 60 mg/day in 95% of patients; at the end of follow-up, 37% were still taking 60 mg/day, while 38.7% were taking 90 mg/day and 16.1% were taking 120 mg/day. Results Median diuresis was 5-6 liters over 24 hours. A mean reduction in GFR of 12.5% (which was maintained for the next 12 months) was observed after initiation of therapy as a likely effect of tubulo-glomerular feedback. Monthly blood tests were performed to monitor side effects (hyper/hyponatremia, increased bilirubin and/or transaminases, etc.). Therapy was withdrawn by 2 patients (3.2%) due to aquaresis, while it was discontinued in 3 patients (4.8%) according to clinicians’ decision due to hepatic damage (3-fold increase in transaminases and/or bilirubin normal values). No significant alteration in natremia was observed in any patient. An increase in CK was observed in one patient, leading to momentary discontinuation of therapy. One patient withdraw therapy because of CKD’s progression to stage 5 after 2 years of therapy. Conclusion Results of this observational study show that Tolvaptan therapy was well tolerated and the incidence of liver damage was superimposed on that described in the literature. It will be necessary to continue clinical observation over the time and apply Tolvaptan’s therapy to a larger population in order to assess its effects on disease progression.