APOL1 genotyping in kidney transplantation: to do or not to do, that is the question? (contra)

Abstract

Discussions regarding genetic testing for variants in apolipoprotein L1 (APOL1), a gene located on chromosome 22 whose risk variants are strongly associated with end-stage kidney disease (ESKD), in the context of kidney transplantation must address donors (deceased and living) and recipients. In addition, these discussions must occur in the context of known genetic epidemiology regarding APOL1. Specifically, APOL1 risk variants are only found among individuals of African descent, as these variants are derived from exposure to African sleeping sickness that is largely confined to countries along the west coast of Africa. 1 Genovese G. Friedman D.J. Ross M.D. et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010; 329: 841-845 Crossref PubMed Scopus (1388) Google Scholar In other words, not every individual who self identifies as Black or African American will even be at risk for carrying these genetic variants, and in fact, 87% of African Americans do not actually carry 2 APOL1 renal risk variants. 2 Foster M.C. Coresh J. Fornage M. et al. APOL1 variants associate with increased risk of CKD among African Americans. J Am Soc Nephrol. 2013; 24: 1484-1491 Crossref PubMed Scopus (180) Google Scholar More important, among the 13% of African Americans who do carry 2 APOL1 renal risk variants, the presence of these variants alone is insufficient to cause ESKD. 2 Foster M.C. Coresh J. Fornage M. et al. APOL1 variants associate with increased risk of CKD among African Americans. J Am Soc Nephrol. 2013; 24: 1484-1491 Crossref PubMed Scopus (180) Google Scholar We question the rationale for routine testing of all African American donors and recipients. Those in favor would likely remind us of the Hippocratic Oath—first do no harm—and that it is our duty to assign and avoid such risk. Paternalistic strategies such as this, although good intentioned, often overlook the broader context of how such dogmas may eliminate patient autonomy in decision making and even exacerbate existing disparities. In the following paragraphs, we will lay the foundation for the case against routine APOL1 testing in kidney transplantation with the hope of encouraging a more balanced approach to the care of donors and recipients alike. APOL1 genotyping in kidney transplantation: a look into the futureKidney InternationalVol. 100Issue 1PreviewChronic kidney disease (CKD) and end-stage kidney disease disproportionately affect individuals with African ancestry.1 African Americans have a lower rate of referral for kidney transplantation and lower graft survival than other ethnic groups.2 The risk of end-stage kidney disease is higher in Black living donors compared with White counterparts.3 Variants in the apolipoprotein L1 (APOL1) gene (G1: S342G and I384M; and G2: del N388 and Y389) explain most of this disparate risk for nondiabetic kidney disease, with the magnitude of risk varying depending on the clinical phenotype. Full-Text PDF