APOL1 Kidney Disease
In the United States, Black individuals comprise 13% of the population but account for 30% of the cases of end-stage kidney disease (ESKD). Two common variants of the apolipoprotein L1 gene (APOL1) are responsible for much of the nondiabetic chronic kidney disease risk among Black individuals.
The wild-type APOL1 gene is called G0 and the two common variants are named G1 and G2. The risk of kidney disease associated with the APOL1 G1 and G2 alleles follows a recessive inheritance pattern.Individuals with 2 alleles of APOL1 G1 or G2 variants (G1/G1, G2/G2, or G1/G2) have an increased risk of kidney disease and are collectively known as the APOL1 high-risk genotype.
Among Black individuals in the US, the G1 allele frequency is 22% and the G2 allele frequency is 13%. More than 5 million people in the US have a high-risk APOL1 genotype. Individuals possessing a high-risk APOL1 genotype have a 15% to 30% lifetime risk of developing ESKD. Approximately 75% of Black individuals in the US with focal segmental glomerulosclerosis (FSGS) have been estimated to have a high-risk APOL1 genotype.
Besides FSGS, Black individuals with a high-risk APOL1 genotype are more likely to develop hypertensive kidney disease, lupus nephritis, and HIV-associated nephropathy compared to Black individuals with with a low-risk genotype.
APOL1 genetic screening may be indicated for Individuals with recent West African heritage who have nondiabetic CKD, proteinuria, or a family history of kidney disease. Prospective kidney donors with recent West African heritage may benefit from APOL1 genetic testing because donors with a high-risk APOL1 genotype have a greater decrease in post-donation kidney function and are more likely to develop ESKD. Also, kidney transplants from donors with a high-risk APOL1 genotype have a shorter allograft survival compared to transplants from donors with a low-risk APOL1 genotype.
Reference
Hopper TH and Olabisi O. APOL1-Mediated Kidney Disease. JAMA, May 21, 2024; 331:1668-69.
