An overview of frailty in kidney transplantation: measurement, management and future considerations

Abstract

The construct of frailty was first developed in gerontology to help identify older adults with increased vulnerability when confronted with a health stressor. This article is a review of studies in which frailty has been applied to pre- and post-kidney transplantation (KT) populations. Although KT is the optimal treatment for end-stage kidney disease (ESKD), KT candidates often must overcome numerous health challenges associated with ESKD before receiving KT. After KT, the impacts of surgery and immunosuppression represent additional health stressors that disproportionately impact individuals with frailty. Frailty metrics could improve the ability to identify KT candidates and recipients at risk for adverse health outcomes and those who could potentially benefit from interventions to improve their frail status. The Physical Frailty Phenotype (PFP) is the most commonly used frailty metric in ESKD research, and KT recipients who are frail at KT (~20% of recipients) are twice as likely to die as nonfrail recipients. In addition to the PFP, many other metrics are currently used to assess pre- and post-KT vulnerability in research and clinical practice, underscoring the need for a disease-specific frailty metric that can be used to monitor KT candidates and recipients. Although frailty is an independent risk factor for post-transplant adverse outcomes, it is not factored into the current transplant program risk-adjustment equations. Future studies are needed to explore pre- and post-KT interventions to improve or prevent frailty.

Keywords: aging; frailty; kidney transplantation; physical function; survival.

FIGURE 1

Frail individuals are most vulnerable to the numerous health stressors of kidney disease.

FIGURE 2

The continuum of frailty in kidney disease. The figure displays current knowledge on the risk factors, correlates and outcomes of frailty among individuals with kidney disease.

FIGURE 3

Physiology of immunosenescence: the aging immune system. (Panel A) Aging is associated with immunosenescence, resulting in alterations in the immune response. These alterations may require adjustment of immune therapy after KT [109] (Panel A redesigned with permission from Transplantation: November 2015-Volume 99-Issue 11- p 2258-2268, Copyright © 2015 Wolters Kluwer Health [110]). (Panel B) In addition to aging, frailty may also influence immune therapy risks after KT. Novel immune system biomarkers may permit individualization of immune therapy among vulnerable transplant recipients.