Incorporating apolipoprotein L1 testing into evaluation of potential living kidney donors: a single-centre experience

Abstract

Assessment of future risk of end-stage renal disease (ESRD) is an important component of evaluation of potential living kidney donors. Known donor risk factors for ESRD include first-degree relatives, young age, male sex and African descent [1]. In the general population, the presence of two apolipoprotein L1 (APOL1) risk alleles is a key determinant of the excess incidence of ESRD observed in African Americans [2]. In living kidney donors, the effect of the APOL1 genotype on the risk of developing ESRD is unknown. However, the higher risk in black donors and the faster decline in estimated glomerular filtration rate (eGFR) observed post-donation in donors with two APOL1 risk alleles [3] suggests that this group should be considered with caution. The APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) study (NCT03615235) aims to provide prospective data to guide these decisions in the future. In the current absence of prospective data, some centres screen for APOL1 risk alleles in potential donors of African descent. A recent survey of US transplant surgeons and physicians reported that 63% of them intended to use APOL1 testing in the next year [4]. Patient perspectives of APOL1 testing in potential donors are also supportive of this approach [5, 6]. The experience of a policy of testing APOL1 risk alleles in potential donors has not been previously reported. Potential living donors with African ancestry (n1⁄4 20) assessed at our centre since 2016 were genotyped for APOL1 risk alleles (performed by Nephrology Molecular Genetics Laboratory, Weißwasser, Germany). Summary data, including potential donor characteristics, estimated lifetime risk of ESRD and assessment outcome, are presented in Table 1. In this cohort, 30% of potential donors had two APOL1 risk alleles. This is greater than the population allele frequency but similar to the reported prevalence in first-degree relatives of patients with ESRD [7]. Our practice is to estimate donor ESRD risk using both preand post-donation calculators available at www.transplantmodels.com. The available risk calculators are limited by incorporating race but not APOL1 genotype as a variable. While APOL1 status is an important determinant of chronic kidney disease (CKD) risk in young African American potential donors [8], there are currently insufficient data to inform how to incorporate APOL1 status into quantitative risk assessment models. While clinical characteristics and calculated estimated lifetime risk of ESRD were similar between groups, no potential donors with an APOL1 risk genotype were approved for donation. While we do not consider the APOL1 risk genotype to be an absolute contraindication to donation, we have exercised a high degree of caution in counselling these patients—particularly young donors—about the additional risk. In our experience, the information that kidneys from donors with an APOL1 risk