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

项目摘要 相对于来自欧洲美国人（EA）死亡供体（DD）的肾脏，来自 非裔美国人（AA）DD的移植物存活率明显较短。几项具有里程碑意义的研究显示， 来自携带两种载脂蛋白L1基因（APOL 1）风险变体的DD的移植，定义为APOL 1高风险 基因型，有较短的移植物存活。APOL 1相关病变在这些移植物中的大多数失败移植物中检测到。 APOL 1高风险基因型DD。重要的是，许多肾脏移植自具有两种APOL 1风险变异的DD。 不要迅速失败。我们假设APOL 1与其他环境和遗传因素相互作用， DD肾移植早期失败（DDKT）美国国立卫生研究院（NIH）建立了“APOL 1 长期肾移植结局”（APOLLO）U 01联盟在2017年前瞻性地解决 关于AA DDKT中广泛APOL 1基因分型和评估AA肝肾安全性的几个关键问题 捐赠。研究结果可能会改变美国的肾脏分配政策，提高移植物存活率， 将AA DD肾重新分配到较低的（即，更好的）肾供体概况指数（KDPI）分类， 减少优质肾脏的丢弃，增加肾脏移植，更好地保证生活AA的安全性 捐助者和节省费用。此外，受体APOL 1基因型对移植结果的作用是 有争议，阿波罗解决了这个问题。APOLLO联盟包括一个科学和数据 研究中心（SDRC）和13个临床中心（CC），包括我们的中心。我们的CC，“10/14 APOL 1长- 马里兰州大学学院的肾移植结局网络（APOLLO）临床中心 医学部（UMSOM）和医疗中心（UMMC）由4个额外的肾移植项目组成， 森塔拉、乔治敦、乔治华盛顿和国家儿童医院。我们招募了AA的接受者 在APOLLO的初始阶段，DD和LD肾移植和AA活体供体。9/29/22 APOLLO SDRC和Consortium前瞻性地收集了全国3604名AA DD队列的DNA， 正在跟踪4890 DDKT的结果。13名阿波罗CC同意并从2436名 DDKT接收者。在APOLLO第一阶段，我们的马里兰州大学CC招收了65.3%的所有接受者， 阿波罗DDKT与DNA和生物样本（81/124）。我们还招募了32名AA LD和28名AA LDKT 受惠人士在APOLLO第二阶段，我们CC的具体目标是：目标1。前瞻性收集长期 所有APOLLO参与者的后续数据。目标二。提供详细的临床数据和生物标本， 来自我们CC的APOLLO参与者。目标3：便于返回APOL 1基因型结果。影响：APOL 1 基因分型有可能减少AA供体优质肾脏的丢弃，并增加AA供体的存活率。 整体移植数量。确定改变表型的次要环境或遗传因素 结果将改善所有移植受者的同种异体移植物存活率和生活质量。

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.