The kidney donor profile index (KDPI) incorporates factors known to affect allograft survival; among them, African ethnicity is a variable considered to adversely affect graft outcome. Risk variants of Apoliproprotein L1 (APOL1) gene have been recently linked to chronic kidney disease in individuals of African ancestry. Retrospective data suggest that the presence of two APOL1 risk variants in the donor can affect long-term allograft outcomes. These data will need to be validated in prospective cohorts and studied in donors of African ancestry, including the unique population of Latinos of African Descent which will be captured by our network design (Florida/Puerto Rico/US Virgin Islands).
Aim 1 of this application will validate long-term graft outcomes in recipients of organs from deceased and living donors of African descent carrying two APOL1 risk variants when compared to less than two risk variants.
Aim 2 will compare recipient outcomes between Latinos of African Descent and Blacks (African Americans and African Caribbeans) as well as capture potential interactions with donor-, recipient- and transplant-related ?second hits?.
Aim 3 will focus on the clinical consequences of donation from individuals carrying two APOL1 risk variants and will develop translational tools for the study of ApoL1 biology to be shared with the APOLLO Network and with the scientific community. We have engaged a unique team of interdisciplinary and interinstitutional collaborators which includes five Organ Procurement Recovery Agencies as well as eight transplant centers serving Florida, Puerto Rico and the US Virgin Islands along with UNOS support. In addition, we are collaborating with geneticists funded by a NIH-U54 grant focused on genetic studies in diverse patient populations. To leverage our expertise, we have engaged world renowned experts in the field of ApoL1 biology/genetics as well as our Clinical and Translational Science Institute. These relationships along with our previous expertise in large multi-center longitudinal cohorts, such as NEPTUNE and CureGN, will aid in the successful development of this study at a national level.
Certain genetic variants of a gene called Apoliproprotein L1 (APOL1) have been recently linked to kidney disease in individuals of African ancestry. Studies suggest that kidneys donated by patients with these genetic variants may negatively impact the long-term function of the transplanted organ and may put kidney donors at risk to develop high blood pressure and/or kidney disease. Before organ donation can be denied to a category of patients carrying these genetic variants, a large national scale study based on a strong network-based team effort is needed. Furthermore, the risk attributable to APOL1 genotype needs to be studied in all populations carrying a certain degree of African ancestry, such as Latino patients from the Southeast US found within our region. In order to achieve this, we have engaged a unique team of interdisciplinary and interinstitutional collaborators including five Organ Procurement Recovery Agencies as well as eight transplant centers serving Florida, Puerto Rico and the US Virgin Islands.
