APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors.
APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors.
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DOI：
10.1097/tp.0000000000000969
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发表时间：
2016-01
期刊：
影响因子：
6.2
通讯作者：
Divers J
中科院分区：
文献类型：
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作者：
Freedman BI;Pastan SO;Israni AK;Schladt D;Julian BA;Gautreaux MD;Hauptfeld V;Bray RA;Gebel HM;Kirk AD;Gaston RS;Rogers J;Farney AC;Orlando G;Stratta RJ;Mohan S;Ma L;Langefeld CD;Bowden DW;Hicks PJ;Palmer ND;Palanisamy A;Reeves-Daniel AM;Brown WM;Divers J
两种载脂蛋白L1基因（APOL1）肾风险变异体在供体和非洲裔美国人（AA）受体种族与死亡供体肾移植（DDKT）AA供体移植物存活率较差。为了检测影响已故AA肾供体同种异体移植物存活的其他因素，在其他AA肾供体中对APOL1肾脏风险变体进行基因分型。APOL1基因型与移植受者科学登记处中478例新分析的DDKT的结局有关。对受者年龄、性别、种族、群体反应性抗体水平、HLA配型、冷缺血时间、供者年龄和扩展标准供者进行多变量分析。对先前报告中的478例移植和675例DDKT进行了联合分析。仅限于新的478例DDKT的完全校正分析复制了APOL 1-双肾风险变异肾受者的肾移植物生存期较短（HR 2.00; p = 0.03）。对来自AA供体的1153例DDKT的综合分析显示，供体APOL 1高风险基因型（HR 2.05; p = 3 × 10 − 4）、供体年龄较大（HR 1.18; p = 0.05）和受体年龄较小（HR 0.70; p = 0.001）对同种异体移植物存活率有不利影响。尽管在许多APOL1-双肾风险变异肾的接受者中观察到移植物存活延长，但随访血清肌酐浓度高于零/一APOL1-肾风险变异肾的接受者。竞争风险分析显示，APOL1影响肾移植物存活，但不影响受体存活。供者年龄和APOL1基因型之间的相互作用对移植肾存活率无显著影响。DDKT后，可重复观察到APOL 1-双肾风险变异供体的肾移植物存活率较短。年龄较小的受者和年龄较大的供者对移植肾存活率有独立的不良影响。
Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors. APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel reactive antibody level, HLA match, cold ischemia time, donor age, and expanded-criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed. Fully-adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1-two-renal-risk-variant kidneys (HR 2.00; p=0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR 2.05; p=3×10−4), older donor age (HR 1.18; p=0.05), and younger recipient age (HR 0.70; p=0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1-two-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than in recipients of zero/one APOL1-renal-risk variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were non-significant. Shorter renal allograft survival is reproducibly observed after DDKT from APOL1-two-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.