Frailty and Transplantation

Abstract

Consequences of aging are gaining clinical relevance. In transplantation, aging and immunosenescence impact treatment and outcomes. The impact of aging, however, will critically depend on distinguishing healthy, chronological aging from biological aging that may result into frailty. Approximately 15% of individuals older than 65 years are frail, and it is expected that this condition will gain more clinical relevance with an expected increase to greater than 20% over the next 5 years. Clearly, frailty impacts various general aspects of health care and organ transplantation in particular including patient selection, waitlist management and treatment after transplantation. In general, frailty has been characterized by a compromised physiological reserve and an augmented vulnerability. In comparison to healthy aging, inflammatory markers and cytokines are increased in frail older adults. Thus, modifications of the immune response, in addition to physical limitations and changes of metabolism, are likely to impact outcomes after transplantation. Here, we provide a risk assessment of frailty at the time of transplant evaluation and review effects on outcomes and recovery after transplantation. Moreover, we summarize our current understanding of the pathophysiology of frailty and consequences on immune responses and metabolism.

Report from the American Society of Transplantation on frailty in solid organ transplantation

“…1 Frailty symptoms have been linked to disease severity such as the model for end-stage liver disease and sodium (MELDNa) score in liver transplantation. Pathophysiological mechanisms of frailty and aging somewhat overlap.…”

“…1 Identifying potential reversible components contributing to frailty associated with organ failure could allow for education of transplant candidates and referring providers, identify opportunities for intervention, optimize timing for transplantation, and improve outcomes. It is an independent domain of risk, overlapping with but distinct from comorbidity (such as physiologic aging) and disability; and portends worse outcomes for patients with end-stage organ disease and patients undergoing solid organ transplantation.…”

Impact of Immune-Modulatory Drugs on Regulatory T Cell

“…In addition, IL-6 renders Tconvs resistant to Treg suppression and directly destabilizes Treg by inhibiting FOXP3 expression 195-197 . IL-6 has been implicated in frailty, which is an emerging risk factor for poor transplant outcomes 198,199 . Thus, IL-6 critically regulates Treg number and function, and the level of IL-6 in patients may impact to transplant outcomes.…”

ExplorinG frailty and mild cognitive impairmEnt in kidney tRansplantation to predict biomedicAl, psychosocial and health cost outcomeS (GERAS): protocol of a nationwide prospective cohort study

“…Its 10‐minute administration time suits it to routine clinical application (Exterkate et al . ). (2) The STCS‐developed Expanded Biopsychosocial Framework for Transplant Research (described by De Geest et al .…”