Background
APOL1 gene risk variants (G1: S342G and I384M; and G2: del N388 and Y389) significantly contribute to genetic risk of chronic kidney disease (CKD), particularly in people living with HIV (PLWH). Shorter renal allograft survival has been demonstrated in kidney transplant recipients (KTR) without HIV where either donor or recipient kidney genotype included a high-risk phenotype (two APOL1 risk alleles).
Methods
Genomic DNA was extracted from Peripheral blood mononuclear cells (PBMC) from deceased kidney donors with HIV, as well as KTR with HIV that were transplanted as part of the seminal HIV+-to-HIV+ transplant study in Cape Town, South Africa. APOL1 genotypes were genotyped by TaqMan probe assays (ABI, Foster City, California) specific for APOL1 G1 SNPs (rs73885319 and rs60910145) and the G2 deletion (rs717185313).
Results
Genomic DNA was available for 21 donors and 43 recipients. Recipients were older (median age=37; IQR=33-48), evenly split between male (51%) and female (49%), and were black African (91%) or mixed ethnicity (9%). Donors were significantly younger (Age=31; IQR=26-40; p=0.006), primarily male (76%), and had a significantly more diverse ethnicity (57% black African, 33% mixed ethnicity, 10% white; p=0.004). Donors had relatively low rates of APOL1 high-risk alleles with seven (33.3%) possessing 1 risk allele, and zero with two risk alleles. Conversely, KTR had significantly higher rates of high-risk alleles, with 17 with two risk alleles (39.5%), and 5 with one risk allele (11.6%). HIV associated nephropathy (HIVAN) was the original cause of native kidney failure in 15 of the 17 (88.2%) KTR with two APOL1 variants. 38 KTR had donor APOL1 typing available of whom 12 (31.6%) received kidneys from donors with one risk allele. Over five years of follow-up post transplantation, a composite outcome of graft failure, development of HIVAN, or rejection in the graft was significantly higher in KTR whose donor had one versus zero APOL1 risk alleles [9/12, (75%) versus 9/12 (35%) respectively, p=0.03; Figure 1]. This composite outcome was not associated with recipient APOL1 status [composite outcome 8/15, (53%) in those with 2 risk alleles versus 10/23, (43%) in those with 0/1 risk allele, p=0.55].
Conclusions
Dual APOL1 risk variant status is frequent in South African PLWH undergoing kidney transplantation. In addition, graft outcomes were worse in those who received kidneys from donors with HIV and one high-risk APOL1 allele.
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