Black patients with a high-risk apolipoprotein 1 (APOL1) genotype have increased risks of kidney failure even if they do not have proteinuria, a new study finds.

Investigators combined data from 4855 patients from the African American Study of Kidney Disease and Hypertension (AASK) and Chronic Renal Insufficiency Cohort (CRIC). Of the combined cohort, 374 patients had a high-risk genotype, defined as 2 high-risk alleles in the APOL1 gene.

In adjusted models, a high-risk APOL1 genotype was significantly associated with a 1.9-, 1.4-, and 2.0-fold increased risk for kidney failure among patients with minimal and moderate proteinuria at baseline and no proteinuria at any time point, respectively,  Eugene Lin, MD, of the University of Southern California in Los Angeles, and colleagues reported in Kidney Medicine. High proteinuria was not significantly associated with kidney failure.

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The investigators defined minimal proteinuria as a urinary protein-creatinine ratio (UPCR) of 0.22 mg/mg or less, moderate proteinuria as a UPCR of 1 mg/mg or less but higher than 0.22 mg/mg, and high proteinuria as a UPCR greater than 1 mg/mg.

Kidney failure risk was not significantly increased for Black patients without the high-risk genotype compared with non-Black patients.

“Although kidney damage from the high-risk APOL1 genotype is mediated in part by the development of proteinuria, kidney damage may occur through a mechanism independent of proteinuria,” Dr Ku’s team explained.

“Providers should consider screening for the high-risk APOL1 genotype, especially among Black patients without proteinuria in populations with chronic kidney disease.”

According to the investigators, screening may allow clinicians to intensify general treatments to slow kidney disease progression. Targeted therapies are currently under investigation.


Nguyen A, Suen SC, Lin E. APOL1 genotype, proteinuria, and the risk of kidney failure: A secondary analysis of the AASK (African American Study of Kidney Disease and Hypertension) and CRIC (Chronic Renal Insufficiency Cohort) studies. Kidney Med. December 2022 4(12):100563. doi:10.1016/j.xkme.2022.100563