BACKGROUND AND AIMS: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and the fourth-leading cause of kidney failure. Over the past two decades, various studies have been conducted to characterize the natural history of ADPKD and investigate impacts of potential treatments on disease progression. Previously, we created a pooled longitudinal database of unique subjects from nine studies to evaluate and analyze outcomes. The database was expanded to include data from two recent tolvaptan (TOL) trials (156-13-210 and 156-13-211). Here, we describe the baseline characteristics of the expanded pooled population.
METHOD: Data from 11 ADPKD studies (from 2001 to 2018, sponsored by Otsuka or National Institutes of Health) were combined and divided into two groups: TOL and standard of care (SOC). TOL consisted of trial subjects initiating treatment in one of seven trials (156-04-250, 156-04-251, 156-06-260, 156-09-284, 156-09-290, 156-08-271, and 156-13-210); SOC included subjects from placebo arms of two TOL randomized trials (156-04-251 and 156-09-290), all standard blood pressure control arms in the HALT-PKD trials, and subjects from two observational studies (156-10-291 and CRISP). Subjects in the placebo arm of study 156-13-210 received TOL for 5 weeks before randomization and were therefore included in the TOL group. Eligible subjects who completed an early TOL study continued TOL treatment in the extension study 156-08-271 and/or in a second extension study 156-13-211. Estimated glomerular filtration rate (eGFR) was calculated in all studies using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Total kidney volume (TKV) was measured by magnetic resonance imaging and available in all studies except 156-13-210, 156-13-211, and HALT-PKD study B.
RESULTS: The pooled analysis included 7,117 eligible subjects (TOL: 2,928; SOC: 4,189) from the United States (47.5%) and other countries. The two cohorts had similar age (mean age, 43.6 vs. 44.1 years) and sex distribution (50.5% male vs. 45.2% male). The TOL group had more white subjects (90.5% vs. 80.7%) and fewer Hispanic subjects (4.0% vs. 12.6%), a lower baseline mean eGFR (60 vs. 70 mL/min/1.73 m2), more in chronic kidney disease (CKD) stage 3 or above (58.1% vs. 41.0%), and more frequent history of signs of rapid disease progression (e.g., nephrolithiasis, hematuria, urinary tract infection). Among 4,917 subjects with TKV assessments, mean baseline TKV was higher in the TOL group (1,817 mL) compared with SOC (1,627 mL).
CONCLUSION: In this large, longitudinal database of unique subjects with ADPKD, distinct differences exist in some baseline characteristics of the TOL and SOC groups. Compared with the previous database, the expanded database doubled the size of the TOL group and included more subjects who were older and with advanced chronic kidney disease stage. This database provides a diverse ADPKD population to assess outcomes.
