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 US kidney transplants from African American kidney donors to determine their effect on transplant outcomes. In addition, the post- donation health and kidney function of African American living kidney donors will be assessed. We are applying to be the APOLLO Scientific and Data Research Center (SDRC) for this NIH Funding Announcement. Shorter renal allograft survival is observed for transplantations from deceased African American kidney donors, relative to deceased European American kidney donors. Reasons for this are unknown, but retrospective reports suggest that presence of two apolipoprotein L1 gene (APOL1) renal-risk variants in kidney donors may contribute to the disparity. These 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, but rare in other racial/ethnic groups. APOL1 genotype data 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 in order to optimize renal allograft and patient survival. This information may better inform physicians about organ quality prior to decisions on allocation are made and regarding the safety of living kidney donation. Before this genotypic data can be used clinically, a prospective national study is required to evaluate all kidney transplantation outcomes from African American donors and recipients of their kidneys based on APOL1 genotypes. Information lacking from retrospective studies needs to be collected, including recipient APOL1 genotypes, renal histologic data in failed allografts and presence or development of BK viral infections, donor specific antibodies, and acute rejections after kidney transplantation. We will perform the following activities for the APOLLO Network: overall study coordination, assist with preparation of the final protocol and Manual of Procedures, develop data tracking tools and the study website, collect and archive clinical and outcomes data, perform genotyping, statistical analyses, assessment of the primary outcome ?time to allograft failure in transplanted kidneys from African American donors, based on donor APOL1 genotypes? and create a bio-repository. We will longitudinally assess vital status, kidney function and proteinuria in living African American kidney donors based on APOL1 genotypes. Prospective assessment of the effects of kidney donor APOL1 genotypes on serum creatinine concentration, estimated glomerular filtration rate, and proteinuria in transplant recipients with functioning allografts will also be performed. 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.
Genetic information in the apolipoprotein L1 gene (APOL1) from African American donors of kidneys and transplant recipients may provide more accurate assessments of the likelihood of long-term survival of transplanted kidneys and optimize matching of donors with recipients. This application is submitted in response to the National Institutes of Health request for applications for the APOL1 Long-term Kidney Transplant Outcomes Network (APOLLO) Scientific and Data Research Center and proposes to prospectively evaluate effects of donor and recipient APOL1 genotypes in kidney transplants from African American donors performed at all US transplant programs. Results from the national APOLLO study have the potential to transform the processes of organ allocation and informed consent in kidney transplantation, optimize survival of patients after kidney transplantation, and determine the safety of living kidney donation.
|Freedman, Barry I; Julian, Bruce A (2018) Evaluation of Potential Living Kidney Donors in the APOL1 Era. J Am Soc Nephrol 29:1079-1081|
|Ma, Lijun; Divers, Jasmin; Freedman, Barry I (2018) Mechanisms of injury in APOL1-associated kidney disease. Transplantation :|