Test code: 1291

Clinical use

• Assist evaluation of a potential donor for kidney transplantation

Clinical background

Two variants in the APOL1 gene, known as G1 and G2, increase risk for various types of chronic kidney disease (CKD), such as focal segmental glomerulosclerosis, HIV-associated nephropathy, and hypertension-attributed end-stage kidney disease (ESKD).1 These APOL1 risk variants are mostly limited to individuals with recent West sub-Saharan African ancestry.1,2 About 10% to 15% of African American individuals have a high-risk APOL1 genotype (ie, carry 2 risk variants).2 The estimated risk of CKD among these individuals is 15% to 20%,1 about 41% greater than that of individuals with a low-risk genotype (ie, carrying 0 or 1 risk variant).3

In the kidney transplantation setting, a donor's high-risk APOL1 genotype may increase risks for both the donor and the recipient. Living kidney donors with high-risk genotypes may have a greater decline in kidney function and a higher risk of CKD than donors with low-risk genotypes.4,5 For transplant recipients, a high-risk genotype in a deceased donor is associated with shorter allograft survival.6,7 The risk of premature allograft loss associated with a high-risk genotype in a living donor is currently unknown.

Given the potential risks associated with APOL1, testing for APOL1 risk variants during the evaluation of living donors may help inform decisions on kidney donation. Transplantation outcomes obtained from the APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) study will likely aid in the development of clinical practice guidelines for APOL1 testing.8 Interim recommendations from the American Society of Transplantation's Living Donor Community of Practice indicate that all potential donor candidates who self-report African ancestry—including African, African American, Afro-Caribbean, and Black Hispanic/Latinx—should receive counseling on APOL1 and the risk of ESKD.9 Though individuals with North African or mixed ancestry are less likely to have a high-risk genotype, they should still be counseled on APOL1.9 After counseling and an initial evaluation, donor candidates with known independent risk factors for ESKD (eg, hypertension) who wish to pursue donation and whose ESKD risk is deemed acceptable may be offered APOL1 testing for additional risk stratification.9

Interpretive information

Detection of any 2 APOL1 risk alleles (G1/G1, G2/G2, or G1/G2) indicates an increased risk for developing APOL1-associated CKD. The isolated finding of a high-risk APOL1 genotype should not disqualify a candidate for kidney donation.9 Rather, APOL1 genotype should be considered in conjunction with the individual's full health profile, including clinical presentation, family history, and other laboratory testing results, during pretransplant evaluation.10

This test does not detect variants located outside of APOL1 exon 6. In addition, the test may not detect variants in individuals with mosaicism or allele dropout. False-positive or false-negative results are rare but may occur. Specimens with degraded or a low concentration of DNA, low white blood cell counts, or substances that inhibit PCR (eg, excess heme or heparin) may result in assay failure.

Additional assistance in interpretation of results is available from our genetic counselors by calling 1.866.GENE.INFO (1.866.436.3463).