PRESENTED BY
MARIA  JOSE PEREZ-SAEZ

Presentation Summary

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 [1]. 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 [2]).

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 [3].Further to the fact that two thirds ofhemodialysis (HD) participants are frail [4], frailty defined by Fried score was associated with an increasedrisk of waitlist (WL) mortality [5]. 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 [6].

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 [7].
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 [8].

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 [9].
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 [10].
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[2]).

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 [11].
Physical and mental frailty decrease and disease-specific health-related quality of life (HRQOL) considerable increase within three months after KT [12].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 [13]. Moreover, it was shown that physical exercise can improve outcomes of mobility and functional ability,combined with nutritional interventions together with few pharmacological agents [13]. Prehabilitation may be an effective way to improve functional status of the patient as well[14].A pilot studythat included weekly physical therapy sessions with at-home exercises suggested that prehabilitation may improve post-KT outcomes [15].
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 [16].
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.

References

1. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-56. DOI: 10.1093/gerona/56.3.m146

2. Pérez-Sáez MJ, Outcomes of frail patients after kidney transplantation; June 15, 2019; Budapest, Hungary. View the webcast

3. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. The Lancet. 2013;381(9868):752–762. DOI:10.1016/S0140-6736(12)62167-9

4. McAdams-DeMarco MA, Law A, Salter et al. Frailty as a Novel Predictor of Mortality and Hospitalization in Individuals of All Ages Undergoing Hemodialysis. Journal of the American Geriatrics Society, 2013;61(6): 896-901. DOI: 10.1111/jgs.12266

5. McAdams-DeMarco MA, Ying H, Thomas AG et al. Frailty, Inflammatory Markers, and Waitlist Mortality Among Patients with End-Stage Renal Disease in a Prospective Cohort Study. Transplantation. 2018;102(10):1740-1746. DOI:10.1097/TP.0000000000002213

6. Alfaadhel TA, Soroka SD, Kiberd BA, Landry D, Moorhouse P, Tennankore KK. Frailty and Mortality in Dialysis: Evaluation of a Clinical Frailty Scale. CJASN. 2015;10(5):832-840. DOI: 10.2215/CJN.07760814 

7. McAdams-DeMarco MA, Law A, Tan J et al. Frailty, Mycophenolate Reduction, and Graft Loss in Kidney Transplant Recipients. Transplantation.2015;99(4):805–810. DOI: 10.1097/TP.0000000000000444

8. Garonzik-Wang JM, Govindan P, Grinnan JW et al. Frailty and delayed graft function in kidney transplant recipients. Arch Surg. 2012;147(2):190-3. DOI: 10.1001/archsurg.2011.1229

9. McAdams-DeMarco MA, Law A, Salter ML et al. Frailty and early hospital readmission after kidney transplantation.Am J Transplant.2013;13(8):2091-5. DOI:10.1111/ajt.12300

10. McAdams-DeMarco MA, Law A, King E et al. Frailty and Mortality in Kidney Transplant Recipients. Am J Transplant. 2015; 15(1): 149–154. DOI: 10.1111/ajt.12992

11. McAdams-DeMarco MA, Isaacs K, Darko L et al. Changes in Frailty After Kidney Transplantation. J Am Geriatr Soc. 2015;63(10):2152-7. DOI: 10.1111/jgs.13657

12. McAdams-DeMarco MA, Olorundare IO, Ying H et al. Frailty and Postkidney Transplant Health-Related Quality of Life. Transplantation. 2018;102(2):291–299. DOI: 10.1097/TP.0000000000001943

13. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;2:381(9868):752-62. DOI: 10.1016/S0140-6736(12)62167-9

14. Cheng XS, Myers JN, Chertow GM et al. Prehabilitation for kidney transplant candidates: Is it time? Clin Transplant. 2017;31(8). DOI:10.1111/ctr.13020.

15. McAdams-DeMarco MA, Ying H, Van Pilsum Rasmussen S et al. Prehabilitation prior to kidney transplantation: Results from a pilot study.Clin Transplant. 2019;33(1):e13450. DOI: 10.1111/ctr.13450

16. Kobashigawa J. Dadhania D, Bhorade S et al. Report from the American Society of Transplantation on frailty in solid organ transplantation. Am J Transplant. 2019;19(4):984-994. DOI: 10.1111/ajt.15198

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