Tolvaptan for ADPKD: Two-Years of Follow-up

Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disease, accounts for 10% of causes of end-stage renal disease. In 2014, tolvaptan was approved as the first targeted therapy for ADPKD. However, there are few reported data on the real-world experiences of patients with ADPKD treated with tolvaptan. Judith Fatima Martins Munoz, MD, PhD, and colleagues in Spain conducted a study designed to characterize the effectiveness and safety profile of patients during the first 2 years of treatment with tolvaptan.

Results of the retrospective observational study were reported during a poster session at Kidney Week 2019. The poster was titled Two Years of Follow-Up Experience with Tolvaptan Treatment in Autosomal Dominant Polycystic Kidney Disease.

The study cohort included 143 patients with ADPKD with chronic kidney disease stage (CKD) 1 to 4 who were treated with tolvaptan. Baseline data were collected from 15 centers in Madrid, Spain; the data included laboratory values and kidney volume.

Mean follow-up was 8.7 months, 51% of the participants were women, mean age was 42.7 years, mean baseline estimated glomerular filtration rate was 63 mL/min/1.73 m2, and mean urine osmolality was 445 mOsm/kg. At baseline, 19.6% of participants had stage 1 CKD, 34.3% had stage 2, 27.3% had stage 3a, 16.8% had stage 3b, and 2.1% had stage 4. Total kidney volume was 1695; class of Mayo Clinic classification was: 1B, 0.7%; 1C, 23.8%; 1D, 31.5%; and 1E, 24.5%. Median dose achieved was 100.69 mg in 4.9 weeks.

The rate of adverse events was 74.1%; 68.6% of those were related to increased aquaresis (thirst, polyuria, nocturia, and polydipsia). Liver-enzyme levels were elevated in 14 cases; there were no reported cases of severe liver injury.

After 10.9 months, 31 patients (21.6%) discontinued treatment. The primary reasons for discontinuation were aquaretic effects (86%), elevation of liver-enzyme level (7%), and other (3.5%). Nine patients of the 31 who discontinued reinitiated treatment after a median of 7.02 months. The overall adherence rate was 84.6%. Renal function at 1, 6, 12, 18, and 24 months was 59.83 mL/min/1.73 m2; 56.58 mL/min/1.73 m2, 58.38 mL/min/1.73 m2, 60.21 mL/min/1.73 m2, and 62.87 mL/min/1.73 m2, respectively.

In conclusion, the authors said, “In our experience tolvaptan could be considered as a safe drug in patients with ADPKD. The adherence of the treatment was good, with similar data obtained in TEMPO 3:4 trial. Due to adverse events, it is necessary to monitor the enzyme liver levels, but no cases of fatal liver damage were reported. The renal function remained stable after two years of treatment.”

Source: Martins Munoz JF, Gutierrez-Martinez E, Ortiz A. Two years of follow-up experience with tolvaptan treatment in autosomal dominant polycystic kidney disease. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2019 (Abstract TH-PO841), November 7, 2019, Washington, DC.