Apolipoprotein L1 and kidney transplantation.

Abstract

Consistent associations between variants of the apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy have been reported in individuals of African descent. Donor APOL1 genotype has also been linked to shorter renal allograft survival. This review summarizes recent advances in understanding the biology of APOL1 and their implications to kidney donors and recipients. Approximately 12-13% of African Americans have two renal risk APOL1 variants but most do not develop kidney disease. Although the exact mechanisms linking APOL1 genotype to renal injury are not known, evidence from new experimental models suggests APOL1 mutations may accelerate age-related podocyte loss. Recent epidemiological studies indicate potential kidney donors with high-risk APOL1 variants have increased risk of chronic kidney disease (CKD) and donors with high-risk APOL1 variants have lower estimated glomerular filtration rate (eGFR) than those with low-risk variants. The absolute risk of CKD in otherwise healthy individuals carrying high-risk APOL1 mutations is likely low. Recent studies suggest high-risk APOL1 mutations in kidney donors are linked to shorter graft survival and lower postdonation eGFR. APOL1 genotyping may be used as one of many factors that contribute to assessment of the risk of postdonation CKD and informed decision making.