DESCRIPTION (provided by applicant): Recent trends in kidney transplantation (KT) indicate that more vulnerable patients are waiting to receive kidney transplants than ever before, but transplant providers currently have limited tools or guidance to risk-stratify KT candidates. Perhaps as a result, many candidates are likely to be inactivated or die on the waiting list instead of receiving a transplant. The supply of organs is limited, and candidates for KT must often wait for years before receiving a transplant. Prolonged exposure to poor kidney function has complex negative impacts on patient health, including chronic inflammation and vascular calcification, plausibly leading to steep rates of health decline in certain waitlisted patients tht result in lower rates of KT and inferior outcomes after KT. The goal of this career development award is to characterize patterns of health decline in KT candidates and implement metrics, using existing knowledge in the aging literature, to identify KT candidates who are experiencing accelerated health decline while awaiting KT. Given the heterogeneity of health status on the waitlist, it is imperative that clinicians have objective measures that capture early signs of healh decline so that timely interventions or alternative KT strategies can be implemented to improve patient outcomes. The central premise of this grant is that prolonged exposure to chronic kidney disease (CKD) and renal replacement therapy results in accelerated health decline in many KT candidates, a process that may explain several poor waitlist outcomes including the increasing proportion of inactivated candidates. I propose a series of studies to discover the patterns of decline in physical and cognitive function in KT candidates and the biologic processes that may explain this decline, with the following specific aims: 1) To discover how metrics of physical and cognitive function predict access to KT, inactivation, de-listing and death among individuals in the CRIC study with advanced CKD; 2) To prospectively implement longitudinal metrics of physical and cognitive function into the transplant evaluation of incident KT candidates at a single center in order to evaluate associations with inactive status, de-listing, and death; and 3) To compare clinician evaluation to objective physical and cognitive metrics on the ability to predict adverse transplant-related outcomes among a prospective cohort of waitlisted KT candidates. I am a clinical instructor currently funded by an NIH F-32 grant, with board certification in Internal Medicine and Nephrology and a Masters in Clinical Epidemiology from the University of Pennsylvania. I have also completed the American Transplant Society accredited kidney transplant fellowship at the University of Pennsylvania. This NIDDK K-23 Career Development Award will enable me to develop research aimed at optimizing the assessment and care of vulnerable kidney transplant candidates, with the goal of making ongoing and lasting research contributions as an independent physician-scientist and national leader in the fields of nephrology and kidney transplantation.

PUBLIC HEALTH RELEVANCE: Patients with advanced kidney disease can benefit from kidney transplantation but many are disqualified for transplant or die on the waiting list, most likely because their health worsens before they can receive a transplant. We propose a series of projects to characterize the relationship between health status and kidney transplant outcomes. Our studies include analysis of data from the Chronic Renal Insufficiency Cohort (CRIC) Study, using tests of strength and memory to evaluate which kidney transplant candidates may be most vulnerable to poor outcomes at the University of Pennsylvania Transplant Center, and comparing the accuracy of these tests to traditional clinical evaluation of patients.