Wake Forest Collaborative Application for an APOLLO Clinical Center

我们正在申请作为APOLLO临床中心参与这项全国性的前瞻性研究。美国国立卫生研究院

We are applying to participate as an APOLLO Clinical Center in this national prospective study. The NIH APOL1 Long-term Transplantation Outcomes Network (APOLLO) Collaborative U01 will perform a national prospective evaluation of donor and recipient APOL1 renal-risk variants in all U.S. kidney transplantations from African American donors to determine their effects on transplant outcomes. In addition, the health of living African American kidney donors will be assessed. Information that was lacking from prior retrospective studies needs to be collected, including renal histologic data in allograft failures and presence or development of BK viral infections, donor specific antibodies, and acute rejections after kidney transplantation. Our investigative team, led by two PIs with complementary expertise, has led the way in clinical trials to address the marked disparities in African Americans with end-stage kidney disease. Renal transplantations from deceased African American kidney donors do not last as long as those from deceased European American kidney donors. Reasons for this are unknown, but retrospective reports suggest that presence of two apolipoprotein L1 (APOL1) gene renal-risk variants in kidney donors may contribute. These renal-risk variants are common in populations with recent African ancestry (such as African Americans), where they are strongly associated with non-diabetic end-stage kidney disease. In contrast, these risk variants are rare in other ethnic groups. APOL1 genotype data may prove to be clinically useful in those with recent African ancestry in the setting of allocation of deceased donor kidneys for transplantation and assessment of prospective living kidney donors. Genotypic information (precision medicine) may provide more accurate assessment of the likelihood for long-term renal allograft function in donor kidneys, thereby improving the matching of donor kidneys with potential recipients to optimize renal allograft and patient survival. Information may better inform physicians about organ quality prior to decisions on allocation. However, before these genotypic data can be used in the clinical setting, a prospective national study is required to evaluate kidney transplantation outcomes from African American donors and recipients of their kidneys based on APOL1 genotypes. Information lacking from prior retrospective studies will be collected, including renal histologic data in allograft failures and presence or development of BK viral infections, donor specific antibodies, and acute rejections after kidney transplantation. This is the rationale and setting for the current APOLLO trial. In this important multi-site study, our site will work closely with the APOLLO Scientific and Data Research Center and the other participating sites to recruit and prospectively follow eligible kidney donors and transplant recipients based on the APOLLO protocol. Results have the potential to transform the organ allocation and informed consent processes in kidney transplantation, optimize renal allograft survival, reduce the discard of good-quality kidneys, and protect the health of living kidney donors.