Saint Louis University Center for Abdominal Transplantation, St. Louis, Missouri.
Division of Nephrology, Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Curr Opin Nephrol Hypertens. 2020 Nov;29(6):645-655. doi: 10.1097/MNH.0000000000000653.
To summarize the current state of evidence regarding the role of apolipoprotein L1 (APOL1) genotyping in evaluating donors for kidney transplantation.
African ancestry is associated with an increased risk of kidney failure following living donation. Moreover, kidney transplants from African ancestry deceased donors have an increased risk of graft failure. Preliminary evidence suggests that APOL1 genotype may mediate at least a portion of this racial variation, with high-risk APOL1 genotypes defined by presence of two renal risk variants (RRVs). A pilot study 136 African ancestry living donors found that those with APOL1 high-risk genotypes had lower baseline kidney function and faster rates of kidney function decline after donation. To date, three retrospective studies identified a two-to-three times greater risk of allograft failure associated with kidneys from donors with high-risk APOL1 genotype. Active research initiatives seek to address unanswered questions, including reproducibility in large national samples, the role of 'second hits' injuries, and impact of recipient genotype, with a goal to build consensus on applications for policy and practice.
As evidence evolves, APOL1 genotyping may have applications for organ quality scoring in deceased donor kidney allocation, and for the evaluation and selection of living donor candidates.
目的综述:总结目前关于载脂蛋白 L1(APOL1)基因分型在评估肾移植供体中的作用的证据现状。
最新发现:非裔血统与活体供肾后肾功能衰竭的风险增加有关。此外,来自非裔血统已故供者的肾移植发生移植物衰竭的风险增加。初步证据表明,APOL1 基因型可能至少部分介导了这种种族差异,高风险 APOL1 基因型由存在两种肾脏风险变异(RRV)定义。一项针对 136 名非裔血统活体供者的初步研究发现,具有高风险 APOL1 基因型的供者在捐赠前具有较低的基线肾功能和更快的肾功能下降速度。迄今为止,三项回顾性研究发现,与具有高风险 APOL1 基因型的供者的肾脏相关联的同种异体移植失败风险增加了两到三倍。目前正在开展积极的研究计划,以解决未解答的问题,包括在大型全国样本中的可重复性、“第二击”损伤的作用以及受者基因型的作用,目标是就政策和实践的应用达成共识。
总结:随着证据的不断发展,APOL1 基因分型可能适用于已故供者肾脏分配中的器官质量评分,以及对活体供者候选者的评估和选择。