CureGN Study Rationale, Design, and Methods: Establishing a Large Prospective Observational Study of Glomerular Disease

• Type of Material: Article
• Authors: Laura H. Mariani, University of Michigan; Andrew S. Bomback, Columbia University; Pietro A. Canetta, Columbia University; Michael F. Flessner, National Institute of Diabetes and Digestive and Kidney Diseases; Margaret Helmuth, Arbor Research Collaborative for Health; Michelle A. Hladunewich, University of Toronto; Jonathan J. Hogan, University of Pennsylvania; Krzysztof Kiryluk, Columbia University; Patrick H. Nachman, University of Minnesota; Larry Greenbaum, Emory University
• Language: English
• Date: 2019-02-01
• Publisher: W B SAUNDERS CO-ELSEVIER INC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 National Kidney Foundation, Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1053/j.ajkd.2018.07.020
• Title of Journal or Parent Work: AMERICAN JOURNAL OF KIDNEY DISEASES
• Volume: 73
• Issue: 2
• Start Page: 218
• End Page: 229
• Grant/Funding Information: Funding for the CureGN consortium is provided by UM1DK100845, UM1DK100846, UM1DK100876, UM1DK100866, and UM1DK100867 from the NIDDK. Patient recruitment is supported by NephCure Kidney International. As indicated in the Author list on the Title page (and in the Authors’ Contributions section), NIH staff participated in study design and writing the manuscript. Dates of funding for first phase of CureGN are 9/16/2013-5/31/2019. The funders of this study had no role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.
• Keywords: IGA NEPHROPATHY; CHILDREN; Life Sciences & Biomedicine; RENAL SURVIVAL; MEMBRANOUS NEPHROPATHY; Science & Technology; DIGITAL PATHOLOGY; Urology & Nephrology; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; NEPHROTIC SYNDROME; STEROID-RESISTANT; KIDNEY-DISEASE; CLINICAL-TRIALS
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Biostatistics; Health Sciences, Pathology

Abstract

Rationale & Objectives: Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death. Study Design: Multicenter prospective cohort study. Setting & Participants: Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded. Exposures: Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year. Outcomes: Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events. Analytical Approach: The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years’ initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0 mL/min/1.73 m2 in estimated glomerular filtration rate per year. Limitations: Current follow-up can only detect large differences in ESKD and death outcomes. Conclusions: Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.