Supplementary Material for: Genetics May Predict Effectiveness of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease

<b><i>Background:</i></b> 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 (<i>PKD1</i> and <i>PKD2</i>) on the treatment effects of tolvaptan is not well documented in the literature. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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 m² in the <i>PKD1</i> truncating group, −3.3 to −2.4 mL/min/1.73 m² in the <i>PKD1</i> non-truncating group, −3.1 to −1.6 mL/min/1.73 m² in the <i>PKD2</i> group, and −1.9 to −2.6 mL/min/1.73 m² in the group with no <i>PKD1/2</i> 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 m², respectively. Compared with the group of patients with any <i>PKD1</i>/<i>2</i> mutation, the group with no <i>PKD1</i>/<i>2</i> mutation showed significantly less improvement in ΔeGFR/y with tolvaptan (0.6 vs. −0.7 mL/min/1.73 m², respectively; <i>p</i> = 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; <i>p</i> = 0.02). <b><i>Conclusion:</i></b> Patients with ADPKD and no <i>PKD1</i>/<i>2</i> mutation showed less improvement in ΔeGFR/y and the annual rate of increase in TKV with tolvaptan. Detecting <i>PKD1</i>/<i>2</i> mutations may be useful for predicting the effectiveness of tolvaptan.