End stage renal disease (ESRD) disproportionately affects older adults: approximately 60% of dialysis patients are aged e55. On average, older patients who undergo kidney transplantation (KT) have a survival benefit over dialysis. However, referral for KT in older patients is much lower than for other age groups, at almost 1/7th the rate of referral for younger patients. The key challenge lies in identifying the appropriate candidates for KT. The inability to predict which older patients would benefit from KT, and which would be harmed, is one of the most critical dilemmas for patients, transplant physicians and referring nephrologists. To date, older KT candidates have been naively evaluated using models designed for younger patients based on registry data. We hypothesize that risk metrics specific to older patients, but not captured in national registries or other conventional studies, will significantly improve risk prediction and thus clinical decision-making, referral, and clinical care. One such important metric is frailty, an independent syndrome of decreased physiologic reserve associated with increased hospitalizations, disability and declining cognitive function, and predictive of medical and surgical outcomes. Additionally, systemic inflammation has been identified as a pathway linking frailty to multisystem dysregulation. We also hypothesize that evaluating outcomes specific to older patients will add clinical relevance to risk prediction models. In particular, compared with younger patients, older adults are at risk for disability, cognitive decline, and decreased quality of life, particularly i response to dialysis, major surgery, and immunosuppression. For older adults, conventional models of patient and allograft survival may not be nearly as relevant as ones which take into account these important consequences. We will prospectively quantify the association of frailty, IL-6, other inflammatory markers, and outcomes in 600 older incident dialysis patients and 1,000 older KT recipients. We will then integrate these novel findings with a risk prediction model we previously designed based on registry data, using an innovative approach of standardizing our prospective population to the registry population. The innovative integration of our prospective data with national registry data will provide us the statistical power to identify subtle but important predictors combined with the novelty of metrics specific to older adults. Based on this, we will design a Markov decision process model for older adults with ESRD, comparing outcomes between dialysis and KT. A successful decision process model will be immediately usable by patients, nephrologists, and transplant providers. Transplantation in older adults is a growing field, but risk prediction has been derived from population-based data utilizing age-independent measures. The incorporation of novel aging metrics, such as frailty and IL-6, and outcomes, such as disability, cognitive decline, and quality of life, will greatly improve clinical decision-making in older adults considering KT. This research will address the growing public health challenge of deciding appropriate treatment options for over 300,000 older adults on dialysis in the US.

Public Health Relevance

The inability to predict which older patients would benefit from kidney transplantation, and which would be harmed, is one of the most critical dilemmas for patients, transplant physicians and referring nephrologists; however, the incorporation of novel aging metrics, such as frailty and inflammatory markers, will greatly improve clinical decision-making in older adults considering kidney transplantation. The goal of this project is to develop an innovative decision tool by linking information from an already existing national transplant registry to studies of age-specific metrics that we will conduct. A successful decision tool will b immediately usable by patients, nephrologists, and transplant providers and address the growing public health challenge of deciding appropriate treatment options for over 300,000 older adults on dialysis in the United States.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG042504-03
Application #
8847614
Study Section
Health Services Organization and Delivery Study Section (HSOD)
Program Officer
Salive, Marcel
Project Start
2013-05-15
Project End
2018-04-30
Budget Start
2015-05-01
Budget End
2016-04-30
Support Year
3
Fiscal Year
2015
Total Cost
$591,883
Indirect Cost
$195,228
Name
Johns Hopkins University
Department
Surgery
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
McAdams-DeMarco, Mara A; Ying, Hao; Van Pilsum Rasmussen, Sarah et al. (2018) Prehabilitation prior to kidney transplantation: Results from a pilot study. Clin Transplant :e13450
Haugen, Christine E; Holscher, Courtenay M; Garonzik-Wang, Jacqueline et al. (2018) National Trends in Liver Transplantation in Older Adults. J Am Geriatr Soc 66:2321-2326
Warsame, Fatima; Haugen, Christine E; Ying, Hao et al. (2018) Limited health literacy and adverse outcomes among kidney transplant candidates. Am J Transplant :
McAdams-DeMarco, Mara A; Olorundare, Israel O; Ying, Hao et al. (2018) Frailty and Postkidney Transplant Health-Related Quality of Life. Transplantation 102:291-299
Durand, Christine M; Bowring, Mary G; Brown, Diane M et al. (2018) Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial. Ann Intern Med 168:533-540
Nastasi, A J; McAdams-DeMarco, M A; Schrack, J et al. (2018) Pre-Kidney Transplant Lower Extremity Impairment and Post-Kidney Transplant Mortality. Am J Transplant 18:189-196
McAdams-DeMarco, Mara A; Konel, Jonathan; Warsame, Fatima et al. (2018) Intradialytic Cognitive and Exercise Training May Preserve Cognitive Function. Kidney Int Rep 3:81-88
Van Pilsum Rasmussen, Sarah; Konel, Jonathan; Warsame, Fatima et al. (2018) Engaging clinicians and patients to assess and improve frailty measurement in adults with end stage renal disease. BMC Nephrol 19:8
McAdams-DeMarco, Mara A; Ying, Hao; Thomas, Alvin G et al. (2018) Frailty, Inflammatory Markers, and Waitlist Mortality Among Patients With End-stage Renal Disease in a Prospective Cohort Study. Transplantation 102:1740-1746
Warsame, Fatima; Ying, Hao; Haugen, Christine E et al. (2018) Intradialytic Activities and Health-Related Quality of Life Among Hemodialysis Patients. Am J Nephrol 48:181-189

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