The long-term effect of tolvaptan treatment on kidney function and volume in patients with ADPKD.

Background and hypothesis: The only therapy to ameliorate disease progression in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) is tolvaptan, a vasopressin V2 receptor antagonist. Real-life data on long-term tolvaptan are sparse and limited by restricted follow-up, small patient groups, or lack of a control group. We studied the long-term effect of tolvaptan on kidney function and kidney growth in real-life patients and controls. Moreover, we investigated determinants of long-term treatment efficacy.

Methods: Data from the prospective DIPAK cohort and retrospective OBSERVA cohort were pooled. eGFR was measured at least yearly and total kidney volume (TKV) at least every 3 years. Treatment effects from the start to 6 weeks after initiation of tolvaptan were analyzed as 'acute slope'. After this, endpoints were analyzed as 'chronic slope'. As a control group, we included all patients who were not treated with tolvaptan, assessing change in endpoints before and during theoretical treatment (based on the average time of tolvaptan initiation in tolvaptan-treated patients).

Results: 615 patients (48 ± 12 years, 58.2% female) were included in the full analysis, of which 105 (17.1%) were treated with tolvaptan. The average duration of treatment was 6.1 ± 4.7 years (range: 0.8 to 15.9). After matching, two groups of 92 patients remained for matched analysis. In this analysis, tolvaptan reduced eGFR decline during chronic slope by 14.0% (-4.36 to -3.75 mL/min/1.73m2/year, P = 0.03), versus a decrease of 1.0% (-4.16 to -4.12 mL/min/1.73m2/year, P = 0.9) in the control group. Long-term TKV growth did not significantly change during tolvaptan treatment (5.05 to 5.59%/year P = 0.6). In subgroup analyses, patients with a higher mean osmolar intake had a larger treatment effect of tolvaptan.

Conclusion: In this study, with real-life patient data, long-term follow-up, and a well-matched control group, we found that tolvaptan attenuated long-term kidney function decline but seemed not to influence kidney growth.