OVERTURE: A Worldwide, Prospective, Observational Study of Disease Characteristics in Patients With ADPKD

Ronald D Perrone; Dorothee Oberdhan; John Ouyang; Daniel G Bichet; Klemens Budde; Arlene B Chapman; Berenice Y Gitomer; Shigeo Horie; Albert C M Ong; Vicente E Torres; A Neil Turner; Holly Krasa

doi:10.1016/j.ekir.2023.02.1073

OVERTURE: A Worldwide, Prospective, Observational Study of Disease Characteristics in Patients With ADPKD

Kidney Int Rep. 2023 Feb 13;8(5):989-1001. doi: 10.1016/j.ekir.2023.02.1073. eCollection 2023 May.

Authors

Affiliations

¹ Division of Nephrology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
² Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland, USA.
³ Division of Nephrology, Département de Médecine, Pharmacologie et Physiologie, Hôpital du Sacré-Cœur de Montréal, Université de Montréal, Quebec, Canada.
⁴ Charité-Universitätsmedizin Berlin, Department of Nephrology and Medical Intensive Care, Berlin, Germany.
⁵ Section of Nephrology, University of Chicago School of Medicine, Chicago, Illinois, USA.
⁶ Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
⁷ Department of Urology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁸ Kidney Genetics Group, Academic Nephrology Unit, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK.
⁹ Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
¹⁰ Renal and Autoimmunity Group, MRC Center for Inflammation, University of Edinburgh, Edinburgh, UK.
¹¹ Blue Persimmon Group LLC, Washington, District of Columbia, USA.

Abstract

Introduction: The course of autosomal dominant polycystic kidney disease (ADPKD) varies greatly among affected individuals, necessitating natural history studies to characterize the determinants and effects of disease progression. Therefore, we conducted an observational, longitudinal study (OVERTURE; NCT01430494) of patients with ADPKD.

Methods: This prospective study enrolled a large international population (N = 3409) encompassing a broad spectrum of ages (12-78 years), chronic kidney disease (CKD) stages (G1-G5), and Mayo imaging classifications (1A-1E). Outcomes included kidney function, complications, quality of life, health care resource utilization, and work productivity.

Results: Most subjects (84.4%) completed ≥12 months of follow-up. Consistent with earlier findings, each additional l/m of height-adjusted total kidney volume (htTKV) on magnetic resonance imaging (MRI) was associated with worse outcomes, including lower estimated glomerular filtration rate (eGFR) (regression coefficient 17.02, 95% confidence interval [CI] 15.94-18.11) and greater likelihood of hypertension (odds ratio [OR] 1.25, 95% CI 1.17-1.34), kidney pain (OR 1.22, 95% CI 1.11-1.33), and hematuria (OR 1.35, 95% CI 1.21-1.51). Greater baseline htTKV was also associated with worse patient-reported health-related quality of life (e.g., ADPKD Impact Scale physical score, regression coefficient 1.02, 95% CI 0.65-1.39), decreased work productivity (e.g., work days missed, regression coefficient 0.55, 95% CI 0.18-0.92), and increased health care resource utilization (e.g., hospitalizations, OR 1.48, 95% CI 1.33-1.64) during follow-up.

Conclusion: Although limited by a maximum 3-year duration of follow-up, this observational study characterized the burden of ADPKD in a broad population and indicated the predictive value of kidney volume for outcomes other than kidney function.

Keywords: autosomal dominant polycystic kidney disease; cohort; disease progression; natural history; observational; patient-reported outcomes.

Associated data

ClinicalTrials.gov/NCT01430494