Writen by Jasna Trbojevic-Stankovic
Reviewed by Maria José Pérez-Sáez
Frailty is defined as a clinical syndrome in which three or more of the following criteria arepresent: unintentional weight loss, self-reported exhaustion, weakness, slow walking speed, and low physical activity . Depending on the inclusion criteria, many kidney transplantation (KT)patients can be put into categories of Vulnerable, Mildly frail and Moderately frail, according to Clinical Frailty Scale (CFS)(slide 9 ).
Frailty is a state of increased vulnerability after a stressor event, which increases the risk of adverse outcomes. An obviously small insult, for example, minor infection or new medication, can consequently change the patient’s health state, from mobile to immobile or from independent to dependent (Figure 1).
Vulnerability of frail elderly people changes their health status after a minor illness, such as urinary tract infection, sothat these patients undergo a larger deterioration and might not return to baseline homoeostasis .Further to the fact that two thirds ofhemodialysis (HD) participants are frail , frailty defined by Fried score was associated with an increasedrisk of waitlist (WL) mortality . In order to take the severity of frailty into account as a prognosticator of mortality among 390 incident chronic HD patients, anotherstudy demonstrated that the higher frailty CFS score was associated with higher mortality .
Effects of kidney transplant on frail patients
Tolerance to drugs, complications, readmissions to the hospital, and mortality are the usual issues of KT on patients with frailty.
Firstly, the majority of recipients will require mycophenolate mofetil (MMF) dose reduction or discontinuation (MDR) in the first year after KT.Thisis necessary as frailpatients generally poorly tolerate MMF,however,decreasing the dose is going to lead to a higher percentage of death-censored graft survival. MDR represents a reduction in immunosuppression to less than 2000 mg per day for MMFand less than 1440 mg per day for mycophenolic acid .
Secondly, the study including 183 KT patients pointed at the fact that preoperative frailty was independently associated with a risk ofdelayed graft function (DGF), especially for frail KT recipients from a deceased donor with cold ischemia time longer than 24 hours .
Moreover, since around 30% of KT patients are readmitted to the hospital within 30 days of discharge, it was shownthat frail KT recipients were more prone to early hospital readmissions (EHR) regardless of age than their nonfrail counterparts. Consequently, frailty improved the capability to predict EHR as well as the classification of KT recipients .
Finally, mortality in frail patients was the goal of the study that determined that the nonfrail patients hadthe highest rate of survival, compared to intermediately frail and frail KT participants. It was concluded that frailty was strong and independent risk factor for post-KT mortality .
Pre-transplant evaluation at Hospital del Mar, Spain
The first part of an ongoing observational prospective study of 343 KT patients consists of analysis of patient’s demographic, social, clinical, and analytical variables, frailty, dependencyand depression, as well as bioimpendance assessment during the visit to the KT WLnephrologist and KT nurse. The patient can be included in the KT WL at the second visit to KT WL nephrologist, the urologist and KT nurse. The follow-up is done every six to twelve months together with yearly frailty assessment. The evaluation showed that the frailty patients were more likely to be women, diabetics, coming from HD modality; they were more dependent regarding the physical activity and had higher depression test scores. Bioimpendance test showed that that the fat tissue index was higher in frail patients.
Frailty and age were independent risk factors for surgical complications whereas frailty was an independent risk factor for early 90-day readmission (unpublished data, slide 25).
Change in frailty after kidney transplant
A prospective cohort study demonstrated that after KT, in adult recipients of all ages, frailty initially increased, then decreased and finally improved within three months, suggesting that pre-KT frailty was not an irreversible state. The factors associated with changing in frailty score were DGF, diabetes mellitus and previous frailty .
Physical and mental frailty decrease and disease-specific health-related quality of life (HRQOL) considerable increase within three months after KT .Furthermore, in order to improve perspectives of patients after KT, it is important to do comprehensive geriatric assessment, to detect and assess frailty in patients so that a plan for treatment and follow-up can be developed . Moreover, it was shown that physical exercise can improve outcomes of mobility and functional ability,combined with nutritional interventions together with few pharmacological agents . Prehabilitation may be an effective way to improve functional status of the patient as well.A pilot studythat included weekly physical therapy sessions with at-home exercises suggested that prehabilitation may improve post-KT outcomes .
It is important to mention the Consensus Conference on transplantation related frailty which discussed the features of frailty among kidney, liver, heart and lung recipients and concluded that18% of patients on the WL for KT and 20% of KT recipients were frail. It was noted as difficult to stratify and uniform the definition of frailty, but asitwas associated with lower post-transplant survival, physical exercise, therapy and rehabilitation were suggested to regain functional status .
In future research, it is important to comparefrailty metrics for patient outcomes on the WL as well as identify novel measures of frailty, such as biomarkers, imaging and body composition analysis. It is essential to understand the role of cognition and the way to measure it in the frail phenotype in KT candidates as well as to measure frailty and its prognostic value in the peri-transplant period.Serially collecting patient reported outcomes such as quality of life and coordinating trials of prehabilitation is necessary together with determining whether pre-transplant interventions improve WL outcomes and after-transplant outcomes.