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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK105207-05
Application #
9752537
Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2015-09-10
Project End
2020-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Drexel University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19102
Brown, Justin C; Harhay, Michael O; Harhay, Meera N (2018) Self-reported major mobility disability and mortality among cancer survivors. J Geriatr Oncol 9:459-463
Harhay, Meera N; McKenna, Ryan M; Boyle, Suzanne M et al. (2018) Association between Medicaid Expansion under the Affordable Care Act and Preemptive Listings for Kidney Transplantation. Clin J Am Soc Nephrol 13:1069-1078
Harhay, Meera N; Xie, Dawei; Zhang, Xiaoming et al. (2018) Cognitive Impairment in Non-Dialysis-Dependent CKD and the Transition to Dialysis: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis 72:499-508
Harhay, Meera N; Harhay, Michael O; Ranganna, Karthik et al. (2018) Association of the kidney allocation system with dialysis exposure before deceased donor kidney transplantation by preemptive wait-listing status. Clin Transplant 32:e13386
Harhay, Meera Nair; Jia, Yaqi; Thiessen-Philbrook, Heather et al. (2018) The association of discharge decisions after deceased donor kidney transplantation with the risk of early readmission: Results from the deceased donor study. Clin Transplant 32:e13215
Brown, Justin C; Harhay, Michael O; Harhay, Meera N (2018) Anthropometrically predicted visceral adipose tissue and blood-based biomarkers: a cross-sectional analysis. Eur J Nutr 57:191-198
Brown, Justin C; Harhay, Michael O; Harhay, Meera N (2017) Physical activity, diet quality, and mortality among sarcopenic older adults. Aging Clin Exp Res 29:257-263
Lee, Dong Heun; Boyle, Suzanne M; Malat, Gregory E et al. (2017) Barriers to listing for HIV-infected patients being evaluated for kidney transplantation. Transpl Infect Dis 19:
Brown, J C; Harhay, M O; Harhay, M N (2017) Appendicular Lean Mass and Mortality among Prefrail and Frail Older Adults. J Nutr Health Aging 21:342-345
Brown, Justin C; Harhay, Michael O; Harhay, Meera N (2017) Anthropometrically-predicted visceral adipose tissue and mortality among men and women in the third national health and nutrition examination survey (NHANES III). Am J Hum Biol 29:

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