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Published on: June 23, 2015
Tolvaptan and Autosomal Dominant Polycystic Kidney Disease Progression in Individuals Aged 18-35 Years: A Pooled
Fouad T Chebib1, Neera Dahl2, Xiaolei Zhou3
1Mayo Clinic Division of Nephrology and Hypertension, Jacksonville, FL.
Rational & Objective:
Data are limited regarding the long-term efficacy of tolvaptan in adults aged 18-35 years with autosomal dominant polycystic kidney disease (ADPKD) at increased risk of rapid progression. We assessed the effects of tolvaptan within a larger population of younger adults and over longer follow-up than individual clinical trials could provide.
Study Design:
Pooled database study.
Setting & Study Populations:
A consolidated clinical study database with ADPKD patients aged 18-35 years.
Selection Criteria For Studies:
Studies that enrolled patients who received either tolvaptan or standard-of-care treatment not including tolvaptan.
Data Extraction:
Annual rate of change in estimated glomerular filtration rate (eGFR) and time to kidney failure.
Analytical Approach:
For individuals participating in multiple studies, their data were longitudinally linked to extend the follow-up period. We matched tolvaptan-treated patients with controls based on age, sex, chronic kidney disease stage, eGFR, and, where possible, Mayo Imaging Classification. We compared eGFR decline between groups using mixed-effects modeling.
Results:
The matched analysis set encompassed 204 tolvaptan-treated individuals and 204 controls. Median follow-up was 4.6 years for the tolvaptan group and 1.7 years for controls. In the mixed-effects model, the eGFR decline rate (in mL/min/1.73 m2/year) was -2.58 for the tolvaptan cohort and -4.28 for controls. This indicates reduction in the eGFR decline rate by 1.69 mL/min/1.73 m2/year (95% confidence interval: 0.87-2.52; P < 0.001) with tolvaptan, a 40% improvement. Extrapolating eGFR over 35 years, tolvaptan could delay kidney failure onset by approximately 11 years.
Limitations:
Median follow-up was shorter in the control cohort than the tolvaptan cohort. The projection of time to kidney failure assumed a linear model of eGFR decline.
Conclusions:
This analysis offers insights into the anticipated treatment benefits of tolvaptan for young adults with ADPKD. These findings are crucial for weighing treatment benefits against any associated risks.
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