Apolipoprotein L1 genetic testing in prospective kidney donors: Have we reached a breakthrough or an impasse?

Abstract

Molecular testing, including apolipoprotein L1 (APOL1) sequencing, has recently become more accessible for use in the clinical setting. Although there is a strong association between APOL1 and kidney disease, only a small minority of African American kidney disease patients are estimated to have an APOL1 high-risk genotype. In addition, the lifetime risk for developing kidney disease among individuals with two risk alleles is estimated to be very low. The low prevalence suggests that it follows a two-hit model, where a secondary factor, such as environmental or genomic modifiers, is required to develop kidney disease. We still have a limited appreciation of factors that can act as a “second hit,” and it is unclear whether the hyperfiltration that follows donor nephrectomy constitutes as a “second hit” for the disease. One does not yet know the burden of APOL1 risk alleles among prospective living donors. Now that APOL1 genetic testing is available, and in the absence of prospective data, the role of APOL1 genotyping in live kidney donor candidate selection remains uncertain. There are several ethical issues concerning the use of genetic testing to determine donor eligibility, which can impact the development of policy around APOL1 genetic testing, release of results, and counseling.

Keywords

• african american
• apolipoprotein l1 gene
• apolipoprotein l1
• chronic kidney disease
• donor evaluation
• genetic susceptibility
• high-risk allele
• kidney donors
• risk stratification