LAY SUMMARY: Younger patients with autosomal dominant polycystic kidney disease (ADPKD) may face difficult decisions about initiating treatment. In this analysis, conducted among patients aged 18-35 years using existing data from clinical trials and observational studies, patients receiving tolvaptan were matched and compared with patients receiving standard of care (SOC) alone. Results from the study support that treatment with tolvaptan is associated with a slower rate of decline in kidney function compared with SOC. Furthermore, extrapolations suggest a significant potential delay in time until kidney failure onset for patients treated with tolvaptan. Altogether, these results can help guide patient-doctor conversations about the risks and benefits of treatment initiation among younger patients with ADPKD.
BACKGROUND: Tolvaptan has demonstrated efficacy in slowing kidney function decline relative to placebo in pivotal clinical trials among patients at risk of rapid progression. Previous data among patients aged 18-35 were limited to 3 years in TEMPO 3:4. This study aimed to assess the treatment effect of tolvaptan compared with SOC alone on the annual rate of change of estimated glomerular filtration rate (eGFR) among patients aged 18-35 years using pooled data for up to 5.5 years of follow-up.
METHODS: From the pooled ADPKD database, patients receiving tolvaptan (REPRISE, TEMPO 3:4, and their extension studies) were matched 1:1 with patients receiving SOC (CRISP, HALT-PKD, and OVERTURE) on baseline chronic kidney disease stage, sex, age, eGFR, and ADPKD risk class (when available). CRISP and HALT-PKD data were provided by NIDDK CR, a program of the National Institute of Diabetes and Digestive and Kidney Diseases. eGFR data for up to 5.5 years were used to fit a mixed model that included treatment, time, baseline eGFR, and time-by-treatment interaction as covariates and patient-specific intercepts and slopes (for time) as random effects.
RESULTS: The matched analysis set included 204 pairs with mean baseline eGFR of 93 (SD = 25) mL/min/1.73 m2 in both cohorts. Most patients were in chronic kidney disease stage 1 (62.3%) or stage 2 (23.0%). The mean duration of tolvaptan treatment was 4.4 years with a mean compliance rate of 95%. Among patients in the tolvaptan group with available Mayo Imaging Classification (MIC) (n = 180), 74% and 26% were in MIC 1D/E and 1C, respectively. Based on the mixed model, tolvaptan significantly reduced decline in eGFR by 1.69 mL/min/1.73 m2 per year (95% confidence interval, 0.87-2.52; P < 0.001). Extrapolations suggested a potential delay in time until kidney failure onset for patients treated with tolvaptan, assuming maintenance of efficacy over time.
CONCLUSIONS: This analysis of pooled data provides an estimate of treatment effect of tolvaptan among patients aged 18-35 years who often face difficult decisions about treatment initiation. Results about tolvaptan treatment effect along with potential long-term benefits in delaying kidney failure can help aid conversations about the benefit of treatment initiation among these patients.
