Department of Internal Medicine, Section on Nephrology, Winston-Salem, North Carolina, USA.
Am J Transplant. 2011 May;11(5):1025-30. doi: 10.1111/j.1600-6143.2011.03513.x. Epub 2011 Apr 12.
Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with nephropathy in African Americans (AAs). The effect of transplanting kidneys from AA donors with two APOL1 nephropathy risk variants is unknown. APOL1 risk variants were genotyped in 106 AA deceased organ donors and graft survival assessed in 136 resultant kidney transplants. Cox-proportional hazard models tested for association between time to graft failure and donor APOL1 genotypes. The mean follow-up was 26.4 ± 21.8 months. Twenty-two of 136 transplanted kidneys (16%) were from donors with two APOL1 nephropathy risk variants. Twenty-five grafts failed; eight (32%) had two APOL1 risk variants. A multivariate model accounting for donor APOL1 genotype, overall African ancestry, expanded criteria donation, recipient age and gender, HLA mismatch, CIT and PRA revealed that graft survival was significantly shorter in donor kidneys with two APOL1 risk variants (hazard ratio [HR] 3.84; p = 0.008) and higher HLA mismatch (HR 1.52; p = 0.03), but not for overall African ancestry excluding APOL1. Kidneys from AA deceased donors harboring two APOL1 risk variants failed more rapidly after renal transplantation than those with zero or one risk variants. If replicated, APOL1 genotyping could improve the donor selection process and maximize long-term renal allograft survival.
载脂蛋白 L1 基因（APOL1）中的编码变异与非裔美国人（AA）的肾病密切相关。从携带两个 APOL1 肾病风险变异的 AA 供体移植肾脏的效果尚不清楚。在 106 名 AA 已故器官供体中对 APOL1 风险变异进行了基因分型，并评估了 136 例由此产生的肾脏移植的移植物存活率。Cox 比例风险模型测试了移植物衰竭时间与供体 APOL1 基因型之间的关联。平均随访时间为 26.4±21.8 个月。在 136 例移植肾脏中，有 22 例（16%）来自携带两个 APOL1 肾病风险变异的供体。25 个移植物发生衰竭，其中 8 个（32%）具有两个 APOL1 风险变异。一个多变量模型考虑了供体 APOL1 基因型、总体非洲血统、扩展标准供体、受者年龄和性别、HLA 错配、CIT 和 PRA，结果表明，携带两个 APOL1 风险变异的供体肾脏的移植物存活率明显缩短（风险比[HR]3.84；p=0.008），HLA 错配更高（HR1.52；p=0.03），但总体非洲血统不包括 APOL1 则没有。与携带零个或一个风险变异的供体相比，携带两个 APOL1 风险变异的 AA 已故供体的肾脏在肾移植后更快衰竭。如果得到复制，APOL1 基因分型可以改善供体选择过程，最大限度地提高长期肾移植的存活率。
