There are >400,000 older ESRD patients in the United States;adults over 55 are the fastest growing age group, and also the most challenging to treat and counsel. In older ESRD patients, risk prediction for patients undergoing the 2 available treatment modalities -- dialysis and kidney transplantation (KT) -- is based on generic metrics derived from national registries that cover patients of all ages and focus on one dichotomous endpoint (survival/death). These outcomes may be of limited relevance to older ESRD patients who are at high risk of adverse health outcomes of aging (AHOA). Novel risk prediction metrics developed in community-dwelling older adults may be uniquely suited to risk prediction among older ESRD patients. One potentially important metric is frailty, an independent syndrome of decreased physiologic reserve. Systemic inflammation is thought to mediate the association of frailty and AHOA due to increased vulnerability to stressors. Frailty is associated with doubling of dialysis mortality risk and a doubling of early KT allograft dysfunction. However, other outcomes are important for older ESRD patients. In response to dialysis and KT, older patients are at high risk for AHOA (cognitive dysfunction, ADL disability, depression, and low quality of life). We will test the following specific aims in 1 cohort of older dialysis initiates and 1 cohort of older KT recipients: (1) To estimate frailty trajectories and factors associated with frailty decline;(2) To determine the association of frailty and AHOA;and (3) To evaluate the inflammatory pathway between frailty to AHOA. We have designed a mentorship plan that includes in-depth course work in aging research and will be carried out in a well suited environment. The mentorship team includes expertise in aging research, kidney disease research, and mentorship of junior faculty. This team will help the candidate meet her career goals: (1) Widen experience in aging research;(2) Applying for and obtaining R01 grant funding;and (3) Improving treatment and outcomes of older ESRD patients. Our exploration of novel predictors and outcomes specific to older ESRD patients will directly benefit this population, and their providers, by informing risk prediction, helping guide clinical decision making, and possibly even providing insights into underlying biological processes.

Public Health Relevance

Risk prediction in older end stage renal disease (ESRD) patients is currently based on generic metrics derived from national registries that cover patients of all ages and focus on 1 dichotomous endpoint (survival/death). However, the novel incorporation of age-specific metrics, such as frailty, systemic inflammation, and adverse health outcomes of aging, will greatly improve clinical decision-making in older adults considering kidney transplantation. The goal of this project is to develop a prediction model for adverse health outcomes of aging (cognitive dysfunction, ADL disability, depression and low quality of life) in a cohort of dialysis patients and a second cohort of KT recipients. Our exploration of novel predictors and outcomes specific to older ESRD patients will directly benefit this population, and their providers, by informing risk prediction, helping guide clinical decision making, and possibly even providing insights into underlying biological processes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01AG043501-01A1
Application #
8635721
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Salive, Marcel
Project Start
2013-12-01
Project End
2018-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
1
Fiscal Year
2014
Total Cost
$131,229
Indirect Cost
$9,721
Name
Johns Hopkins University
Department
Surgery
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Salter, Megan L; Gupta, Natasha; King, Elizabeth et al. (2014) Health-related and psychosocial concerns about transplantation among patients initiating dialysis. Clin J Am Soc Nephrol 9:1940-8