ESRD-specific physiologic age: improving geriatric transplant prognostication

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Older adults with end stage renal disease (ESRD) who receive kidney transplantation (KT) double their life expectancy. The new kidney allocation system, designed to better match longevity of recipients and allografts, has been in effect for 2 years. During this time, access to KT among older adults has plummeted; with rates declining 10% for candidates aged 61-70 and 24% for those aged >70. The core problem is that the United Network for Organ Sharing (UNOS) decided that longevity matching for the new allocation system would be based on Estimated Post-Transplant Survival (EPTS), a simple model that only includes chronologic age, diabetes, time on dialysis, and prior transplant. EPTS has poor predictive power among older recipients; the c- statistic of EPTS for older recipients is 0.59, which is lower than the c-statistic of 0.67 for younger recipients. We hypothesize that a measure of physiologic reserve will more accurately stratify risk among older KT recipients than chronologic age. Our preliminary work suggests that the Fried frailty phenotype, is associated with poor post-KT outcomes. While our findings are encouraging, it is unlikely that this construct captures all the dimensions of physiologic reserve associated with ESRD. It is likely that some attributes of the Fried frailty phenotype are not even relevant for this population. We believe an ESRD-specific measure of physiologic reserve, beyond frailty and/or other conventional measures, would greatly improve risk stratification. UNOS and the transplant community might be reluctant to add a new variable to the purposefully parsimonious EPTS score, which was debated for 15 years. Our novel approach, supported by the upcoming UNOS president, is to replace chronologic age with physiologic age in the model. The overarching goal of our research will be to develop a physiologic age calculator and test whether replacing chronologic age with physiologic age improves prognostication for older adults with ESRD. To achieve these goals, we will leverage existing data and collect new data within an ongoing longitudinal cohort study of 5,500 ESRD patients. We will abstract new data on components of physiologic reserve from the parent study and enroll an additional 2,342 new ESRD patients in an ancillary study which will directly measure the physiologic reserve components that cannot be abstracted. We will test the following aims: 1) To elicit and evaluate novel constructs that might quantify physiologic reserve in older ESRD patients; 2) To create a valid, reliable, and generalizable measure of physiologic reserve for ESRD patients; 3) To test if replacing chronologic age with physiologic age improves prognostication in older recipients. This work would improve prognostication for older adults with ESRD, which would benefit patient selection, informed consent, and case-mix adjusted transplant center report cards. Our novel approach to replacing chronologic age with physiologic age has the support of UNOS leadership and could have an immediate impact on organ allocation and prioritization, possibly improving access for older KT candidates.