Dr. Harold I. Feldman is an established patient-oriented researcher and epidemiologist with an extensive track record in successful research in kidney disease and transplantation. He is a faculty member in a large patient-oriented research group on the University of Pennsylvania campus, the Center for Clinical Epidemiology and Biostatistics. In part, through this affiliation, through other resources on the Penn campus, Dr. Feldman has available to him all of the components necessary for successful patient-oriented research including state-of-the-art research/clinical laboratory services as well as biostatistical and data management resources. Dr. Feldman proposes to utilize support from a Midcareer Research Award to further his career goals of learning, in more depth, the methodology for immunological evaluation of individuals with kidney disease, expand his expertise in epidemiological methods relevant to his established program in applied patient-oriented research, and expand his skills as an educator and mentor. The proposed patient-oriented NIH-funded research project is in its first of five years and will examine the determinants the potential etiologies of the disturbingly short kidney allograft survivals among black ESRD patients. Hypothesized explanations for these differences include poorer matching for major class histocompatibility antigens (HLA), as cadaveric donors are principally white; less complete matching of minor histocompatibility antigens between donors and black recipients, again because of racial differences; greater alloreactivity among blacks; and lower compliance with immunosuppressive therapy among blacks. Newly available, state-of-the-art methods for DNA-based typing of both class I and class II HLA loci have provided the tools to determine accurately HLA differences between unrelated individuals, especially among black Americans, that may be of great functional significance. We are now be able to assess if poor HLA matching accounts for the poor allograft outcomes among black Americans. In addition, new methods for the electronic measurement of drug compliance offer an opportunity to examine its role in these poor outcomes. In the proposed study we will use both of these methods in a regionally-based cohort study of approximately 1000 transplant recipients in to re-examine the intermediate and long-term race-allograft survival relationship.
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