Surrogate End Points in Apolipoprotein L1–Associated Kidney Disease

Key Points Apolipoprotein L1 (APOL1) high-risk genotype had higher risk of 3-year GFR-related surrogate end points and long-term kidney failure than those with the low-risk genotype. No consistent difference in surrogate–clinical outcome associations by APOL1 genotype, supporting the use of surrogates in APOL1 kidney disease. Background Surrogate end points for the clinical outcome of kidney failure have been accepted by the US 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 Black participants in the Atherosclerosis Risk in Communities study ( N =3071), Chronic Renal Insufficiency Cohort ( N =998), and African American Study of Kidney Disease and Hypertension ( N =609). Surrogate end points included a 3-year 30% and 40% decline in GFR, doubling of urine protein–creatinine ratio, and >3 ml/min per 1.73 m 2 per year decline in GFR. Clinical outcomes included kidney failure requiring KRT, heart failure, cardiovascular disease, and death after 3 years. Results 22% in the African American Study of Kidney Disease and Hypertension, 18% in the Chronic Renal Insufficiency Cohort, and 13% in the Atherosclerosis Risk in Communities study had the APOL1 high-risk genotype. Participants with the APOL1 high-risk genotype had higher risk of all 3-year GFR outcomes but not doubling of urine protein–creatinine ratio, as well as kidney failure after 3 years. The 3-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 3-year GFR-related end points 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.