APOL1 risk variants (G1 & G2) have a prevalence of 30% and 8%, respectively among African Americans (AAs), and when present in homozygous state, increase the risk of non-diabetic end-stage kidney disease by 7-10 fold. Over 17,000 kidney transplants were performed in 2014, for which AAs accounted for 11% of living donors and 14.2% of deceased donors. The objective of this proposal is to establish the North East Consortium for Transplant outcomes in APOL1 kidney Recipients (NECTAR)-Clinical Center, a collaborative effort between the Icahn School of Medicine at Mount Sinai and Weill Cornell Medical Center, comprising 2 coordinating centers, 15 kidney transplant centers, 9 histocompatibility labs, 5 OPOs and central support from UNOS, representing 72% of all transplants in New York State and 98% of all transplants in New Jersey. The rationale for this proposal includes the following: (1) evolving current literature suggests that living kidney donors are at increased risk for chronic kidney disease (CKD), hypertension and proteinuria; (2) data point to an increased risk of death-censored graft loss in the presence of 2 APOL1 risk variants in the donor; (3) the association of APOL1 gene variants in living donors with the development of CKD, hypertension and proteinuria has not been characterized; and (4) prospective studies of clinical outcomes in AA and Hispanic living donors and their recipients are lacking.
Our Specific Aims define the key components of the Consortium, namely to recruit the recipients of all donors of AA and non-AA donors of African descent, from the participating centers, over a period of two years to study the impact of APOL1 genotype on post-transplant outcomes, including but not limited to albumin-to-creatinine-ratio, estimated glomerular filtration rate (eGFR) and graft survival. In addition, AA and non-AA donors of African descent living donors will be enrolled and followed longitudinally to determine the role of APOL1 risk variants in the development of hypertension, CKD and end stage renal disease (ESRD) post-donation. Both donors and recipients will be followed longitudinally for three years and biospecimens including blood, urine, stool and biopsies will be banked for the purpose of performing bioassays to identify secondary insults that contribute to or trigger the decline of renal function in either donors or recipients. Appropriate protocols and procedures will be established, including the creation of a web-based electronic data capture tool to collect and track data from research participants and procedures to ensure safe and efficient transfer of data and specimens to the Scientific Data Research Center.
The gene APOL1 have been associated with increased risk of chronic kidney disease in African Americans. The North East Consortium for Transplant outcomes in APOL1 kidney Recipients Clinical Center (NECTAR- CC) will study the impact of this gene on long-term outcomes in renal transplant recipients that receive a kidney from an African American donor and also the impact on kidney function in African Americans that donate a kidney.
