APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) Clinical Center

观察到从已故的非洲裔美国人亲属捐赠者身上移植的肾脏存活率较短 那些来自已故欧美捐赠者的。最近的回顾报告表明， 两种载脂蛋白L1基因(APOL1)在肾捐献者中的存在 导致了这种差异。APOL1肾病风险变异在具有非洲血统的美国人群中很常见 (主要是非裔美国人)，并与非糖尿病患者的终末期肾病密切相关 糖尿病肾病，然而这些风险变异在其他民族中很少见。APOL1基因分型数据之前 可以广泛应用于移植社区，然而，必须进行前瞻性的多中心研究 对非洲血统捐赠者的肾脏结果进行了评估。移植后危重临床 需要收集以前的回顾研究中缺乏的信息，特别是肾脏活检。 数据和关键的潜在修饰因素，如病毒感染的发展，捐赠者特异性抗体，以及 急性排斥反应的发作。美国国立卫生研究院将资助一项全国性的前瞻性研究，以评估APOL1的影响 来自非洲的已故或活体供者肾移植的肾脏风险变异对受者结局的影响 非洲血统和活体非洲血统供者肾切除后的肾脏健康。这项研究将 由多达15个临床中心和一个中央科学数据研究中心(SDRC)组成。《临床》 中心将收集每位参与者的一次性血液样本，用于在国家发改委进行APOL1基因分型，并将 向国家发改委提交受者和活体捐赠者的纵向临床数据，以评估 APOL1基因与慢性肾脏病或终末期肾病的关系。由此产生的结果是 国家研究有可能改变器官分配和知情同意程序 移植非洲血统的捐赠者的肾脏，提高移植肾的存活率，并提供 更好地理解APOL1肾脏风险变异导致肾脏疾病的机制。

Shorter allograft survival is observed for kidneys transplanted from deceased African American donors relative to those from deceased European American donors. Recent retrospective reports have indicated that the presence of two apolipoprotein L1 gene (APOL1) renal-risk variants in the kidney donors significantly contributes to this disparity. APOL1 renal-risk variants are common in U.S. populations with African ancestry (primarily African Americans) and are strongly associated with end-stage renal disease for patients with non- diabetic kidney disease, yet these risk variants are rare in other ethnic groups. Before APOL1 genotypic data can be widely applied in the transplant community, however, a prospective multi-center study must be performed to evaluate outcomes of kidneys from donors with African ancestry. Critical clinical post-transplant information that was lacking in the prior retrospective studies needs to be collected, particularly kidney-biopsy data and key potential modifiers such as development of viral infections, donor-specific antibodies, and episodes of acute rejection. The NIH will fund a nationwide prospective study to assess the impact of APOL1 renal-risk variants on the outcomes of recipients of a kidney from a deceased or living donor with African ancestry and on the kidney health of living donors with African ancestry after nephrectomy. The study will consist of as many as 15 Clinical Centers and a central Scientific Data Research Center (SDRC). The Clinical Centers will collect one-time blood samples from each participant for APOL1 genotyping at the SDRC and will submit longitudinal clinical data for the recipients and living donors to the SDRC to assess the impact of APOL1 genotype on development of chronic kidney disease or end-stage renal disease. The results from this national study have the potential to transform organ allocation and informed consent processes in the transplantation of kidneys from donors with African ancestry, improve renal allograft survival, and provide a better understanding of the mechanisms whereby APOL1 renal-risk variants produce kidney disease.