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

Posttransplant Frailty: Early and Late Outcomes

Early Outcomes Among Frail KT Recipients

Increasing evidence suggests that frail KT recipients are more vulnerable to the immediate surgical and immunologic stressors of KT than nonfrail recipients (Table 2). In a prospective cohort study of 183 KT recipients transplanted between 2008 and 2010, frailty was independently associated with a nearly 2-fold higher risk of delayed graft function (DGF) [adjusted relative risk (aRR) 1.94 (95% CI 1.13–3.36)].[21] Frailty is also associated with a 2-fold higher risk of post-KT delirium [aOR 2.05 (95% CI 1.02–4.13)].[90] These findings suggest that frail KT candidates are likely to require more support during their initial KT hospitalization.

Frail KT recipients and those with physical impairments are also likely to have higher healthcare utilization post-KT. For example, lower extremity impairment at the time of KT, objectively measured by the Short Physical Performance Battery (SPPB), is associated with a longer hospital length of stay following KT.[45] Frail KT recipients are more likely to experience early hospital readmission within 30 days of discharge from KT than nonfrail recipients [45.8% versus 28.0%; aRR for readmission among frail recipients 1.61 (95% CI 1.18–2.19)].[22] Thus, interventions that can improve PF and frailty status prior to KT could have the potential to decrease the number of hospital days and readmissions post-KT and reduce costs.

Longer-term Patient and Graft Survival Outcomes in Frail KT Recipients

The long-term benefits of KT are not uniform or guaranteed, but rather vary based on factors including recipient age, comorbidities, the timing of transplantation and organ quality.[7,94,95] Independent of traditional risk factors, the PFP is associated with a 2.2-fold higher risk of mortality after KT, whereas intermediate frailty is associated with a 1.5-fold higher risk of mortality.[23] Similarly, lower extremity impairment, objectively measured by the SPPB, is associated with a 2.3-fold higher post-KT mortality risk and a 16% absolute increase in 5-year mortality post-KT.[46] With respect to self-reported PF, a retrospective cohort study of 19 242 US KT recipients with linked dialysis center records including SF-12 PCS scores found that lower SF-12 PCS scores were associated with reduced 3-year survival (84% versus 92% for the lowest versus highest quartiles).[41] Nonetheless, KT was associated with a statistically significant survival benefit over dialysis by 9 months for patients in every PF quartile in this study. These results suggest that the survival advantage of KT persists across KT recipients of varying PF.

Post-KT Changes in Frailty Status

KT itself is associated with dynamic changes in frailty status: patients are confronted with surgical and immunologic stressors, but also experience restored kidney function. In a prospective cohort of 349 KT recipients, investigators found that among recipients of all ages, frailty initially worsened in the first-month post-KT but then improved by 3 months post-KT.[20] Furthermore, KT recipients who were frail at KT were more likely than nonfrail recipients to show improvements in physiological reserve over time, suggesting that frailty is potentially reversible with KT.[20] Some evidence suggests that frail KT recipients receive outsized benefits from KT with respect to improvements in health-related quality-of-life (HRQOL). In a retrospective cohort study of 443 KT recipients at two US centers, frail recipients experienced significantly higher rates of improvement in physical HRQOL and kidney disease–specific HRQOL with KT than nonfrail recipients.[92] These studies suggest that carefully selected frail KT candidates can receive substantial benefits from KT.