Determinants of chronic kidney disease in African-American live kidney donors



 DESCRIPTION (provided by applicant): Allan B. Massie, PhD, is an Assistant Professor of Surgery and Epidemiology at Johns Hopkins. He seeks a Mentored Research Scientist Development Award in order to gain training and experience in nephrology, genetic epidemiology, and the conduct of cohort studies and to transition to independent research. Every year, 6000 healthy individuals undergo live donor nephrectomy in the United States to benefit a relative, friend, or stranger with end-stage renal disease (ESRD). The largest cohort study of kidney donors to date - the foundation of the conventional wisdom that "live kidney donation is safe" - involved a > 99% Caucasian population. However, African-American (AA) donors are at elevated risk of post-donation ESRD and death compared to Caucasians. Unfortunately, risk prediction in this critically important population is poor, hampering donor screening and informed consent, depriving AA kidney donors of accurate information about their personal risk after kidney donation, and limiting opportunities to mitigate long-term risk in this population. The proposed research is nested within an ongoing, NIH-funded multicenter cohort study of AA donors. The aims of the project are: 1) to identify the association between high-risk variants of the APOL1 gene and CKD following donation in AA live kidney donors; 2) to identify risk factors for long-term eGFR decline in AA kidney donors; and 3) to compare post-donation eGFR trajectories in AA donors to those in AA nondonors. Aim 1 will implement a nested case-cohort study within the parent study; Aim 2 will draw on donor medical records obtained via the parent study; and Aim 3 will compare eGFR calculated from medical records of the parent study to data from the ARIC and CARDIA cohorts. The proposed research leverages a large cohort of AA donors, but is distinct from the parent study in its study design, novel collection of biologica specimens to understand genetic determinants, and novel collection of longitudinal data to study eGFR trajectories. The research proposal outlines a detailed proposal to give Dr. Massie the training required to complete the research, under the leadership of mentor Dr. Dorry Segev MD PhD and Dr. Josef Coresh MD PhD, drawing from the advice of an advisory team that includes experts in nephrology, genetic epidemiology, study design, and biostatistics. Dr. Segev is a transplant surgeon, Director of Clinical Research in the Division of Transplantation at Johns Hopkins, and PI of the parent study for the proposed research. Dr. Coresh is an epidemiologist, Director of the Cardiovascular Epidemiology Program at Johns Hopkins and leader of the Chronic Kidney Disease Consortium. Dr. Massie hopes eventually to lead independent research programs investigating long-term outcomes of transplant recipients and live organ donors. Completion of the proposed aims will improve risk prediction for AA live kidney donors and prospective donors, aid in medical decision-making, enhance informed consent, and provide vital information relevant to the long-term health outcomes of the 14,000 AA live kidney donors living in the United States.