Surrogate Endpoints in APOL1-Associated Kidney Disease: Evaluation in Three Cohorts

Alix Rosenberg; Carina Flaherty; Amanda Anderson; Lawrence J Appel; Josef Coresh; Jiang He; Jim Lash; Celina Liu; Panduranga Rao; Jonathan Taliercio; Aditya Surapaneni; Morgan Grams; CRIC Study Investigators

doi:10.2215/CJN.0000000000000575

Surrogate Endpoints in APOL1-Associated Kidney Disease: Evaluation in Three Cohorts

Clin J Am Soc Nephrol. 2024 Nov 5. doi: 10.2215/CJN.0000000000000575. Online ahead of print.

Authors

Affiliations

¹ Division of Precision Medicine, Department of Medicine, New York University, New York, New York.
² Department of Epidemiology, School of Public Health, University of Alabama, Birmingham, Alabama.
³ Welch Center for Epidemiology, Prevention, and Clinical Research, Johns Hopkins University, Baltimore, Maryland.
⁴ Aging Institute, Department of Population Health, New York University, New York, New York.
⁵ Department of Epidemiology, Tulane University, New Orleans, Louisiana.
⁶ Division of Nephology, Department of Medicine, University of Illinois, Chicago, Illinois.
⁷ Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, Michigan.
⁸ Department of Kidney Medicine, Cleveland Clinic, Cleveland, Ohio.

PMID: 39499577
DOI: 10.2215/CJN.0000000000000575

Abstract

Background: Surrogate endpoints for the clinical outcome of kidney failure have been accepted by the United States Food and Drug Administration. However, they have not been specifically evaluated in Apolipoprotein L1 (APOL1)-associated kidney disease.

Methods: This random-effects meta-analysis included African-American participants in the Atherosclerosis Risk in Communities (ARIC) study (N=3071), the Chronic Renal Insufficiency Cohort (CRIC; N=998), and the African American Study of Kidney Disease and Hypertension (AASK; N=609). Surrogate endpoints included three-year 30% and 40% decline in glomerular filtration rate (GFR), doubling of urine protein-to-creatinine ratio (UPCR), and >3 ml/min/1.73 m2 per year decline in GFR. Clinical outcomes included kidney failure requiring kidney replacement therapy, heart failure, cardiovascular disease, and death after three years.Results: 22% in AASK, 18% in CRIC, and 13% in ARIC had the APOL1 high risk genotype. Participants with the APOL1 high-risk genotype had higher risk of all three-year GFR outcomes but not doubling of UPCR, as well as kidney failure after three years. The three-year outcomes were strongly associated with kidney failure, with weaker but statistically significant associations with the development of heart failure, cardiovascular disease, and mortality. There were no differences in associations between short-term and long-term clinical outcomes by APOL1 risk status.

Conclusions: Individuals with the APOL1 high risk genotype were more susceptible to three-year GFR-related endpoints and long-term kidney failure than individuals with the APOL1 low-risk genotype. There was no consistent difference in short-term-clinical outcome associations by APOL1 genotype, supporting the use of surrogates in APOL1-associated kidney disease.