CANDIDATE: This proposal is for a K08 Mentored Clinical Scientist Research Career Development Award for Dr. Puttarajappa, a Transplant Nephrologist at the University of Pittsburgh Medical Center. He has completed a Master of Science in Clinical Research and aims to develop into a health services researcher with skills to apply observational data, mathematical modeling and decision analysis to kidney transplantation (KT). Under the mentorship of experts at the University of Pittsburgh, he will pursue courses in survey research, epidemiology, health policy and mathematical modeling in health care. These will allow him to complete his proposed research aims and facilitate transition to an independent investigator. Dr. Puttarajappa will be guided by experts in KT outcomes research (Dr. Hariharan), mathematical modeling and decision analysis (Drs. Kenneth Smith and Mark Roberts), and survey methodology and donor research (Dr. Howard Degenholtz). RESEARCH: Broadly, his aims are to investigate the Utility of Virtual Crossmatch (VXM) in deceased donor KT (DDKT). The 2014 kidney allocation system (KAS) gave high priority to highly sensitized (i.e. higher calculated PRA) waitlisted candidates and allowed for wider sharing of kidney donor profile index >85 kidneys, resulting in increased shipping of organs, higher non-local KT surgeries and increased cold ischemia time (CIT). To assess donor-recipient compatibility and avoid immediate transplant rejection, a physical cell-based crossmatch (XM) is routinely performed prior to KT. VXM is a technique that compares donor human leukocyte antigen(HLA) typing and recipient HLA antibody profile to predict physical XM results. VXM has the potential to decrease CIT in DDKT, which will reduce delayed graft function, rejection, and improve graft and patient survival. Reducing CIT could also reduce organ discard and improve organ utilization.
Specific AIMS for this proposal are 1) Evaluate current crossmatch practices in deceased donor KT among different donor and recipient subgroups, along with assessing perceptions of transplant professionals regarding VXM, 2) Explore if use of VXM is associated with lower CIT and DGF, and if this is different before and after the introduction of KAS and, and 3) Explore if routine application of VXM prior to DDKT has the potential to improve patient outcomes.
These aims will be achieved using a combination of surveys, analysis of data from the United Network of Organ Sharing, and mathematical modeling. His research will identify situations where a VXM will be sufficient to proceed to transplantation without a physical XM. Additionally, findings on national crossmatch practice variation and perceptions of the transplant community towards VXM will help direct future research, changes to histocompatibility protocols and health policy. This award will allow Dr. Puttarajappa to achieve the skills necessary to conduct independent clinical research in KT while simultaneously yielding valuable information on the optimization of crossmatch strategies for DDKT.
Efforts to improve organ utilization along with maximizing function and longevity of transplanted kidneys will allow more patients with end-stage-kidney-disease to benefit from kidney transplantation. This research will use database analysis, surveys and mathematical modeling to identify optimal crossmatch strategies to reduce cold ischemia time in deceased donor kidney transplantation.
