Genetics May Predict Effectiveness of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease

Background: Tolvaptan is the only therapeutic drug for autosomal dominant polycystic kidney disease (ADPKD). The influence of mutations in polycystic kidney disease 1 and 2 genes (PKD1 and PKD2) on the treatment effects of tolvaptan is not well documented in the literature. Methods: We retrospectively evaluated the relationship between genotype and the efficacy of tolvaptan in 18 patients with ADPKD who had been treated at Toranomon Hospital and undergone genetic testing between April 2016 and February 2020. Results: The annual change in estimated glomerular filtration rate (ΔeGFR/y) from before to after tolvaptan was from a median of −5.5 to −2.5 mL/min/1.73 m 2 in the PKD1 truncating group, −3.3 to −2.4 mL/min/1.73 m 2 in the PKD1 non-truncating group, −3.1 to −1.6 mL/min/1.73 m 2 in the PKD2 group, and −1.9 to −2.6 mL/min/1.73 m 2 in the group with no PKD1/2 mutation. The median degrees of improvement of ΔeGFR/y were 2.5 (45%), 0.4 (10%), 0.6 (28%), and −0.7 (−37%) mL/min/1.73 m 2 , respectively. Compared with the group of patients with any PKD1/2 mutation, the group with no PKD1/2 mutation showed significantly less improvement in ΔeGFR/y with tolvaptan (0.6 vs. −0.7 mL/min/1.73 m 2 , respectively; p = 0.01) and significantly less improvement in the annual rate of increase in total kidney volume (TKV) with tolvaptan (−6.7 vs. −1.1%, respectively; p = 0.02). Conclusion: Patients with ADPKD and no PKD1/2 mutation showed less improvement in ΔeGFR/y and the annual rate of increase in TKV with tolvaptan. Detecting PKD1/2 mutations may be useful for predicting the effectiveness of tolvaptan.