APOL1 risk genotype in Europe: Data in patients with focal segmental glomerulosclerosis and after renal transplantation

Abstract

Apolipoprotein L1 (APOL1) risk variants are strongly associated with sporadic focal segmental glomerulosclerosis in populations with African ancestry. We determined the frequency of G1/G2 variants in patients with steroid-resistant nephrotic syndrome/focal segmental glomerulosclerosis with African or French West Indies origin in France and its relationships with other steroid-resistant nephrotic syndrome genes. In a cohort of 152 patients (139 families), the APOL1 risk variants were genotyped: the two risk allele (high risk) genotype was found in 43.1% of subjects compared to 18.9% in a control population (P<0.0001). Compared to patients in the low risk group, patients in the high-risk group were more likely to originate from French West Indies than from Africa. APOL1 high-risk genotype was more frequent in young adult patients, but it was also found in children and it was associated with a bad renal prognosis. APOL1 high-risk genotype was usually not associated with other causative mutation in known monogenic steroid-resistant nephrotic syndrome genes and families in which multiple individuals have focal segmental glomerulosclerosis may have APOL1-associated disease. After renal transplantation, recipients of deceased-donor kidney transplantation from individuals with recent African ancestry possessing two APOL1 high-risk variants have slightly shorter allograft survival. Effects of APOL1 are independent of other traditional risk factors. Recently it was shown that black living kidney donors homozygous for APOL1 high-risk alleles have significantly lower glomerular filtration rate and increased risk of end-stage renal disease after donation. However, APOL1 genotype may not summarize by itself the totality of this risk. We showed that living kidney donors of African ancestry in France with low-risk APOL1 genotype have lower postdonation eGFR increase and lower baseline kidney volume compared to Caucasian donors.