An Overview of Frailty in Kidney Transplantation

Measurement, Management and Future Considerations

Meera N. Harhay; Maya K. Rao; Kenneth J. Woodside; Kirsten L. Johansen; Krista L. Lentine; Stefan G. Tullius; Ronald F. Parsons; Tarek Alhamad; Joseph Berger; XingXing S. Cheng; Jaqueline Lappin; Raymond Lynch; Sandesh Parajuli; Jane C. Tan; Dorry L. Segev; Bruce Kaplan; Jon Kobashigawa; Darshana M. Dadhania; Mara A. McAdams-DeMarco


Nephrol Dial Transplant. 2020;35(7):1099-1112. 

In This Article

Opportunities to Intervene in Pre- and Post-KT Frailty: Structured Exercise Programs, Prehabilitation and Rehabilitation

Interventions to reduce frailty in populations with CKD and ESKD are understudied, although data from interventions tested among frail older patients may be instructive. Interventions to reduce frailty in community-dwelling older adults are most often multidimensional[121] and include exercise training, nutritional supplementation or pharmaceutical agents.[122] They have focused on the reversible phenotypic frailty components (weakness, slowness and low energy expenditure) to delay functional decline and disability rather than to prime patients before a major stressor.[123,124] Interventions that significantly reduce frailty among community-dwelling older adults include physical activity interventions and pre-emptive rehabilitation (i.e. prehabilitation).[125]

Exercise Trials: Data From Populations With CKD and ESKD

It remains an open question as to whether exercise can improve overall vulnerability among CKD and ESKD patients. However, several randomized trials of patients with CKD and ESKD have demonstrated the potential benefits of physical exercise programs to prevent or reverse sarcopenia and improve PF.[126–130] A Cochrane review evaluating the effect of exercise on CKD and KT patients that included 45 randomized controlled trials showed that regular exercise improved physical fitness, cardiovascular dimensions, serum albumin and health-related quality of life.[128] A meta-analysis evaluating 41 trials that compared any regular exercise training for at least 8 weeks with sham or no exercise in CKD and ESKD showed any type of exercise significantly increased aerobic capacity and mid-thigh muscle area (four trials) but found no change in walking capacity.[131] Neither the Cochrane review nor the meta-analysis focused specifically on frail individuals. Small trials have demonstrated the potential for physical therapy programs to benefit frail patients with CKD and ESKD.[83]

Prehabilitation Before KT

Prehabilitation, or intensive exercise therapy prior to an elective surgical intervention, shifts the focus to optimization prior to surgery rather than rehabilitation after surgery.[84] In a recent survey, both clinicians (97%) and patients (94%) agreed that pre-KT prehabilitation could help patients undergoing KT and that prehabilitation could make ESKD patients less frail (clinicians 100%, patients 84%). Additionally, 97% of clinicians and 80% of patients agreed that patients would be interested in pre-KT prehabilitation.[13] In a pilot study,[85] 18 KT candidates participated in weekly physical therapy sessions with at-home exercise. After 2 months, participants improved their physical activity by 64% (P = 0.004). These data suggest that prehabilitation is a promising intervention for KT candidates with frailty. However, larger studies with longer durations of follow-up are likely needed to determine whether exercise programs can improve pre- and peritransplant vulnerability to health stressors.

Posttransplant Rehabilitation

Several studies have investigated the role of exercise therapy in ambulatory KT recipients. Two European centers report efficacy from a structured rehabilitation program post-KT.[132,133] In a US trial (N = 97), an individualized home exercise regimen starting at 1-month posttransplant and monitored with regular phone follow-up improved peak oxygen uptake (a surrogate of cardiopulmonary fitness), muscle strength and self-reported physical functioning compared with usual care at 1 year.[134] The average age in the trial was low (40 ± 13 years in the exercise arm) and 43% of the cohort did not complete the exercise protocol. A subsequent UK trial recruited 60 older patients (age 55 ± 11 years in the exercise arm) within 1 year of KT and tested the effect of 12 weeks of supervised structured exercise classes twice per week for 12 weeks (aerobic versus resistance training versus usual care) and reported improvement in peak oxygen uptake attributable to both aerobic and resistance training compared with usual care.[135] Together, these studies suggest that KT itself improves cardiorespiratory fitness within the first-year posttransplant and that these improvements can be further augmented by aerobic and resistance exercise.