Frailty is an evolving concept in the field of kidney transplantation (KT). First described as a syndrome of decreased physiological reserve or ability to recover from stressors among community-dwelling older adults, it has since been found to be both common among end-stage renal disease patients and associated with posttransplantation morbidity and mortality.1-4 Historically, frailty in the KT setting has been studied as a static marker diagnosed at the time of evaluation for transplantation; however, recent studies have identified changes in frailty status between time points (ie, frail to nonfrail or nonfrail to frail) as predictive of outcomes.5,6 In this issue of Transplantation, Chu et al7 present analysis of factors associated with changes in frailty status between evaluation and KT, and the impact of these changes on post-KT hospitalization length of stay and mortality.
The authors performed a retrospective, single-center observational study leveraging 569 KT recipients at the Johns Hopkins Hospital from November 2009 to September 2017. Frailty is measured at the time of evaluation and KT, and change in frailty status is assessed by 3 approaches: binary state (nonfrail vs frail), 3-category state (nonfrail vs intermediately frail vs frail), and raw frailty score (0–5). During a median time between evaluation and KT of 1.1 years (interquartile range: 0.6–1.9), essentially equal proportions of patients became more frail or less frail, and no factors were independently associated with transition from nonfrail to frail status. For outcomes, increasing frailty by 3-category state or raw score was associated with higher odds of mortality and prolonged hospitalization (≥2 weeks stay), and patients who became less frail had similar outcomes to patients who had stable frailty status.
Overall, the results presented in this article by Chu et al build on the growing body of evidence that frailty is a dynamic process with worsening frailty status conferring increased risk of adverse outcomes. It benefits from a large sample size but is limited by generalizability (single-center study), survivor bias (only patients who survived to KT were analyzed), and possible Hawthorne effect (study participants may alter behavior because of the involvement in study). Any survivor bias would likely support the study’s findings, as frailty is independently associated with mortality in the end-stage renal disease population and study participants who died before KT were excluded from analysis.1 The implications of a Hawthorne effect are uncertain.
The authors show high rates of transition between frailty states during the period from evaluation to KT, and nearly two-thirds of patients experienced a change in raw frailty score. Unfortunately, no independent factors were found to be predictive of worsening frailty (up to 29% of patients) or transition from nonfrail to frail status (up to 9% of patients). These changes are the most important for clinicians to understand, as they offer a chance for early interventions such as prehabilitation to ameliorate this decline rather than reactive interventions on clinical detection of worsening frailty status. One possibility is that factors outside of patient demographics and baseline comorbidities would better predict worsening frailty status, such as health literacy or social support. However, these qualitative factors remain to be elucidated.
High rates of dichotomous changes in frailty score and status without the ability to predict worsening frailty underscore the authors’ suggestion for increased frequency of frailty assessments among KT patients. This brings up 3 key points that the reader must recognize. First, frailty at the time of evaluation should not preclude patients from listing for transplantation. Second, for future studies on the impact of pretransplantation frailty on posttransplantation outcomes, isolated frailty assessment at the time of evaluation will result in a significant misclassification bias for a substantial number of patients. Third, further clinical implementation of frailty assessment necessitates the development of an efficient and clinically relevant assessment tool. The Fried score is too complex and time-consuming for generalized use in the field of transplantation, and there is evidence that simplified scores can be developed (eg, Liver Frailty Index for the cirrhotic population).8,9 The authors should lead the kidney transplant community in these efforts.
1. McAdams-DeMarco MA, Law A, Salter ML, et al. Frailty as a novel predictor of mortality and hospitalization in individuals of all ages undergoing hemodialysis. J Am Geriatr Soc. 2013;61:896–901.
2. McAdams-DeMarco MA, Law A, King E, et al. Frailty and mortality in kidney transplant recipients. Am J Transplant. 2015;15:149–154.
3. McAdams-DeMarco MA, Mara A, King E, et al. Frailty, length of stay, and mortality in kidney transplant recipients: a national registry and prospective cohort study. Ann Surg. 2017;266:1084–1090.
4. McAdams-DeMarco MA, Ying H, Olorundare I, et al. Individual frailty components and mortality in kidney transplant recipients. Transplantation. 2017;101:2126–2132.
5. McAdams-DeMarco MA, Isaacs K, Darko L, et al. Changes in frailty after kidney transplantation. J Am Geriatr Soc. 2015;63:2152–2157.
6. Johansen KL, Lorien S, Dalrymple. Factors associated with frailty and its trajectory among patients on hemodialysis. Clin J Am Soc Nephrol. 2017;2:1100–1108.
7. Chu N, Deng A, Ying H, et al. Dynamic frailty before kidney transplantation—time of measurement matters. Transplantation. 2019;103:1700–1704.
8. Lai JC, Covinsky K, Dodge J, et al. Development of a novel frailty index to predict mortality in patients with end-stage liver disease. Hepatology. 2017;66:564–574.
9. Lai JC, Covinsky K, McCulloch C, et al. The Liver Frailty Index improves mortality prediction of the subjective clinician assessment in patients with cirrhosis. Am J Gastroenterol. 2018;113:235–242.