BACKGROUND: In clinical trials, tolvaptan led to a slower decline in kidney function (vs placebo) among ADPKD patients at risk of rapid progression. The objective of the current study is to evaluate real-world effectiveness of tolvaptan by comparing annual rate of change in kidney function, as measured by eGFR, in adult ADPKD patients treated with and without tolvaptan.
METHODS: From May 2019 to September 2022, 57 US nephrologists completed a web-based survey using medical records of ADPKD patients treated with tolvaptan for ≥2 year (cases). A cohort of ADPKD patients in Mayo class 1C to 1E not treated with tolvaptan was obtained from CRISP, HALT-PKD (data provided by NIDDKCR, a program of the National Institute of Diabetes and Digestive and Kidney Diseases) and OVERTURE studies (controls). Cases and controls were matched 1:1 on baseline age, gender and chronic kidney disease (CKD) stage. Kidney function decline was compared between cases and controls using mixed models, which included treatment, time, and a treatment-by-time interaction as fixed effects and patient-specific intercepts and slopes (for time) as random effects.
RESULTS: Of the 149 cases treated with tolvaptan, controls matched for age, sex and CKD stage were identified for 110 cases. Among these 110 matched pairs, the majority were male (60%), aged 43 (SD: 10.1) years on average, and 76% were in CKD stage 3a or earlier. Mean eGFR at baseline was 60 mL/min/1.73m2 among cases and 63 mL/min/1.73m2 among controls. The annual change in eGFR was -2.23 mL/min/1.73m2 among cases vs -3.62 mL/min/1.73m2 among controls with a statistically significant difference of 1.40 mL/min/1.73m2per year (95% CI: 0.05, 2.74, p =0.042). A second analysis, whereby cases and controls were matched on baseline age, gender and eGFR resulted in 98 matched pairs. In comparison of the 98 matched pairs tolvaptan was associated with a trend in reduction of decline rate by 1.18 mL/min/1.73m2 per year (95% CI: -0.22, 2.58, p =0.097).
CONCLUSION: In the current analysis, tolvaptan showed real world effectiveness in slowing decline in eGFR when compared to matched historical controls, consistent with its efficacy in clinical trials.
