U Maryland Mid-Atlantic APOLLO Research Network Omic and Clinical Center

项目摘要 相对于欧美(EA)已故捐赠者(DDS)的肾脏，移植的肾脏来自 非裔美国人(AA)DDS的移植物存活率显著缩短。几项里程碑式的研究揭示了肾脏 从带有两个载脂蛋白L1基因(APOL1)的DDS移植风险变异，定义APOL1高危 基因型别的移植物存活率较短。在大多数失败的移植物中检测到与APOL1相关的损害 APOL1高危基因DDS。重要的是，许多从DDS移植的肾脏有两个APOL1风险变体 不要很快就失败了。我们假设APOL1与其他环境和遗传因素相互作用导致 DD肾移植早期失败(DDKT)。美国国立卫生研究院(NIH)成立了“APOL1 肾脏移植的长期结果“(Apollo)U01财团将于2017年前瞻性地解决 AA DDKT广泛APOL1基因分型及AA活体肾安全性评估的几个关键问题 捐款。结果可能会改变美国的肾脏分配政策，并导致移植肾存活率的提高。 将AA DD肾脏重新分配到较低(即较好)的肾脏供体概况指数(KDPI)分类，因此 减少高质量肾脏的丢弃和更多的肾脏移植，更好地确保AA患者的生活安全 捐赠者，以及成本节约。此外，受体APOL1基因型别对移植结果的作用是 有争议的阿波罗解决了这个问题。阿波罗联盟包括一个科学和数据项目 研究中心(SDRC)和13个临床中心(CCS)，包括我们的中心。我们的CC，“10/14 APOL1 Long- 马里兰大学临床中心的术语肾移植结果网络(阿波罗) 医学中心(UMSOM)和医学中心(UMMC)由4个额外的肾脏移植计划组成，网址为 森塔拉、乔治敦、乔治华盛顿和国立儿童医院。我们招募了再生障碍性贫血的接受者 阿波罗计划初期的DD和LD肾移植和AA活体捐赠者。到9/29/22， Apollo SDRC和Consortium已经前瞻性地从3604个AA和DDD的国家队列中收集了DNA 以下是4890 DDKT的结果。13个阿波罗CCS同意并收集了2436个生物样本 DDKT收件人。在阿波罗第一阶段，我们马里兰大学CC招收了65.3%的 阿波罗DDKT和DNA和生物样本(124个中的81个)。我们还招募了32名AA LD和28名AA LDKT 收件人。在阿波罗二期，我们CC的具体目标是：目标1.前瞻性地收集长期 所有阿波罗参与者的后续数据。目的2.提供详细的临床数据和生物检疫 来自我们CC的阿波罗参与者。目的3.促进APOL1基因分型结果的返回。影响：APOL1 基因分型有可能减少AA捐赠者丢弃高质量肾脏的情况，并增加 移植的总数量。确定改变表型的次生环境或遗传因素 结果将改善所有移植受者的同种异体移植物存活和生活质量。

Project Summary Relative to kidneys from European American (EA) deceased donors (DDs), kidneys transplanted from African American (AA) DDs have significantly shorter graft survival. Several landmark studies revealed kidney transplants from DDs with two apolipoprotein L1 gene (APOL1) risk variants, defining APOL1 high-risk genotypes, have shorter graft survival. APOL1-associated lesions were detected in most failed grafts from these APOL1 high-risk genotype DDs. Importantly, many kidneys transplanted from DDs with two APOL1 risk variants do not fail rapidly. We hypothesize that APOL1 interacts with other environmental and inherited factors to cause early failure of DD kidney transplants (DDKT). The National Institutes of Health (NIH) established the “APOL1 Long-term Kidney Transplantation Outcomes” (APOLLO) U01 Consortium in 2017 to prospectively address several critical questions regarding broad APOL1 genotyping in AA DDKT and assessing safety in AA live kidney donation. Results could transform the US policy for allocation of kidneys and lead to improved graft survival, reassignment of AA DD kidneys to lower (i.e., better) kidney donor profile index (KDPI) classification and thus lesser discard of good-quality kidneys and more kidney transplants, greater assurance of safety for living AA donors, and cost savings. In addition, the role of recipient APOL1 genotypes on transplant outcomes is controversial and APOLLO addresses this question. The APOLLO Consortium includes a Scientific and Data Research Center (SDRC) and 13 Clinical Centers (CCs), including our center. Our CC, the “10/14 APOL1 Long- term Kidney Transplantation Outcomes Network (APOLLO) Clinical Center” at the University of Maryland School of Medicine (UMSOM) and Medical Center (UMMC) is comprised of 4 additional kidney transplant programs at the Sentara, Georgetown, George Washington, and Children’s National Hospitals. We recruited recipients of AA DD and LD kidney transplants and AA live donors during the initial phase of APOLLO. Through 9/29/22, the APOLLO SDRC and Consortium have prospectively collected DNA from a national cohort of 3604 AA DDs and are following outcomes in 4890 DDKT. The 13 APOLLO CCs consented and collected bio-samples from 2436 DDKT recipients. In APOLLO Phase 1, our University of Maryland CC enrolled 65.3% of all recipients of an APOLLO DDKT with DNA and biosamples (81 out of 124). We also recruited 32 AA LD and 28 AA LDKT recipients. In APOLLO Phase 2, the Specific Aims of our CC are to: Aim 1. To prospectively collect long-term follow-up data on all APOLLO participants. Aim 2. To provide detailed clinical data and biospecimens on APOLLO participants from our CC. Aim 3. To facilitate return of APOL1 genotype results. Impact: APOL1 genotyping has the potential to reduce the discard of good-quality kidneys from AA donors and increase the number of transplants overall. Identifying the secondary environmental or genetic factors that modify phenotypic outcomes will improve allograft survival and quality of life for all transplant recipients.