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

Disclosures

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

In This Article

Potential Roles for Frailty Metrics in Pre-transplantation Settings

KT Candidate Assessment

Given the extent to which KT candidate selection relies on provider perceptions of patients, clinicians who rely solely on clinical acumen for health surveillance of their KT candidates may be likely to misclassify some patient subgroups as frail. In a study of 146 hemodialysis patients from a single dialysis facility, investigators assessed agreement between measured frailty using the Fried et al. criteria to nephrologists' subjective ratings of patient frailty. Nephrologists were inaccurate in their ratings of frailty in 37% of cases, and older adults were the patient subgroup that was most likely to be misclassified as frail.[79] Misclassification of frailty could have large implications for access to KT, as individuals who are inaccurately deemed 'too old, ill or frail' to undergo KT may be less likely to receive transplant education or referral as a result.[79–82] To minimize frailty misclassification that may improperly restrict access to KT, nephrologists may consider augmenting their clinical assessments of potential KT candidates with direct and objective measures of frailty, particularly among older individuals with ESKD.

Unintended Consequences: Frailty Assessments and Transplant Center Practices

Knowledge of frailty in the KT evaluation and selection processes may help to promote individualized care of the most vulnerable patients, permitting timely interventions to improve functional status and listing outcomes.[83–85] However, concerns arise about the potential of unintended consequences when integrating frailty assessments into the KT evaluation process. Earlier in this article, we described evidence that frail individuals with ESKD may still receive a substantial survival benefit from KT compared with remaining on dialysis,[51] and that frailty is potentially reversible with successful KT.[20] Indeed, data suggest that selected older patients and those with long dialysis exposures who receive KT are likely to have better survival and quality of life than similar patients who do not receive KT.[86,87] However, among US KT programs that use a frailty metric during KT candidate assessments, 53% reported that they were less likely to list a frail KT candidate for transplant.[53] These findings have led to concerns that until transplant programs are no longer disincentivized from accepting high-risk KT candidates, individuals with ESKD who are assessed (accurately or inaccurately) to be frail will have reduced access to KT.[11]

Longevity Matching

Given the independent association between frailty and survival, another potential role of frailty metrics is to improve efforts to maximize utility in organ allocation. The revised US Kidney Allocation System (KAS) incorporated a continuous scale called the Estimated Post-Transplant Survival (EPTS) to facilitate allocation of the highest quality deceased donor organs to recipients who are expected to live the longest (i.e. 'longevity matching').[88] Under the revised KAS, candidates with the longest predicted post-transplant survival (EPTS ≤20%) are prioritized for kidneys from donors ranked as 'top 20%' highest quality based on the Kidney Donor Profile Index. The EPTS is based on candidate age, duration of dialysis, diabetes and prior solid organ transplant status, and has a C-statistic of 0.69 (i.e. considered 'good' discriminatory ability).[89] An important area for future research is to examine whether the inclusion of frailty may improve the current longevity matching paradigm.

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