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

Abstract

Dogma, a principle laid down by authorities as incontrovertibly true, is difficult to change once proven incorrect. Considering chronic kidney disease (CKD) in African Americans, the dogma that nearly 40% have mild-moderate hypertension as the cause of nephropathy, low-level proteinuria excludes glomerular disease, and focal segmental glomerulosclerosis is a nonspecific pathology was suddenly struck down with discovery of association between the apolipoprotein L1 gene (APOL1) and nondiabetic CKD. 1 Freedman B.I. Cohen A.H. Hypertension-attributed nephropathy: what's in a name?. Nat Rev Nephrol. 2016; 12: 27-36 Crossref PubMed Scopus (51) Google Scholar ,2 Skorecki K.L. Wasser W.G. Hypertension-misattributed kidney disease in African Americans. Kidney Int. 2013; 83: 6-9 Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar APOL1 G1 and G2 kidney-risk variants (KRVs) display the strongest genetic association in complex disease; G0 is nonrisk. KRVs are found virtually only in populations with recent African ancestry and provide protection from African sleeping sickness. 3 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 Possessing 2 KRVs, autosomal recessive inheritance (G1G1/G2G2/G1G2, 1 KRV from each parent) defines high-risk genotypes with markedly increased risk for CKD. Approximately 13% of African Americans possess 2 KRVs, and 87% have APOL1 low-risk genotypes (∼39% G0G1/G0G2; ∼48% G0G0). 3 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 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