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

项目总结

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.