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.
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.
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