Kidney transplantation (KT) is the preferred mode of renal replacement therapy, with better survival and quality of life for patients suffering from end-stage renal disease.1 However, the shortage of organs and long wait time make it imperative to select candidates carefully for KT. This remains a challenging goal considering the combination of preexisting recipients comorbidities, long wait times from evaluation to transplant, and progression of frailty while on the list for transplantation.
In this regard, the concept of candidate frailty is not new. In general, frailty can be perceived as a decrease in physiological reserve and an individual’s vulnerability to stress. However, this fluid concept remains elusive to objective measurement, as it encompasses several different domains of vulnerability and hence does not lend itself to a uniform definition. A serious fall injury history, although not a core component of the frailty concept, is analogous to frailty assessment since frailty is closely linked to falls.2 Frailty and falls have been more extensively studied in the field of gerontology, which are now being extrapolated to other realms of medicine and surgery including KT.3-6 End-stage renal disease patients with serious fall injury are less likely to be waitlisted or transplanted once on the list.7 And frailty in end-stage renal disease patients is associated with delayed graft function, early hospital readmission, and higher post-KT mortality.4,5,8
In this issue of the journal, Lynch et al9 looked at the relationship between falls on the kidney transplant waitlist and posttransplant outcomes including its impact on graft survival. We applaud the investigators for using an objective event such as a significant fall during the year before transplantation and using it as a potential predictor for subsequent kidney transplant outcomes. In their retrospective national database study of 2247 4 US adults receiving their first kidney transplant from 2011 to 2014, they found that almost 3% of recipients had serious fall injuries, as defined by occurrence of bone fractures, joint dislocations, or brain injury, during the year preceding their transplantation. They identified 33% higher rates of graft failure within 4 years posttransplant among patients who had a serious prior fall. The study also reported an association between serious falls and increased resource utilization and a trend toward increased mortality. The greater resource utilization included longer median length of stay, a 3-fold higher rate of hospitalization, and a nearly 2-fold higher rate of skilled nursing facility use. Those with a serious fall history were more likely to be Caucasian, female, diabetic, or have multiple comorbidities. Though the Estimated Posttransplant Survival score was higher in those with serious falls, 12% of them had an Estimated Posttransplant Survival score <20 and therefore received better quality kidneys, arguably resulting in suboptimal utilization of a scarce resource.
The findings of this study must be accepted with a few caveats in mind.
As with any observational study, the possibility of unidentified or residual confounding remains an issue. In addition, because the final study cohort was limited to those who had both Medicare Parts A and B coverage, a significant chunk of eligible population of presumably younger, healthier, and privately insured patients was excluded, likely leading to overestimation of the association of serious falls with posttransplant outcomes.9 Consequently, the generalization of the study results to a broader waitlisted population may need to be approached with caution. The current study, nevertheless, is timely, adequately powered, and well done. Though several medical and surgical fields have now shown poor outcomes with increasing frailty, much work remains, however, to uniformly define and objectively measure frailty reliably. The current report aptly introduces a component of the frailty construct in the form of serious falls and objectively measures its burden posttransplant.
Several other aspects of frailty and functionality, including grip strength, gait speed, weight loss, self-reported exhaustion, and core muscle measurements, have been assessed, with an attempt to operationalize these into measures of vulnerability.10 So far, no single measure or combination of measures of objective assessment has been universally accepted, and none of these have been validated in the kidney transplant setting. A history of a serious fall could serve as an independent objective marker by itself or in combination with other measures of frailty to prognosticate kidney transplant outcomes.
Moving forward, a concerted effort needs to be made to identify and validate current and new indicators of frailty. This may include not only physical measures but also a cognitive component. The challenge here lies in identifying these factors, exploring important interactions among them, coming to an agreement as to what combination of indicators to use, and then utilizing them to predict kidney transplant outcomes. A comprehensive inclusion of these indicators into pretransplant and waitlist evaluations would go a long way in risk-stratifying patients for transplantation and perhaps offering prehabilitation to those who will benefit the most.
Till such time that the transplant community agrees upon the optimal combination of indicators of frailty to use in the pretransplant setting, inclusion of some measure of vulnerability, be it a serious fall, would add useful information to the evaluation of transplant candidacy. After all, identifying prior falls may prevent future kidney transplant loss.
1. Wolfe RA, Ashby VB, Milford EL, et alComparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341:1725–1730.
2. Pritchard JM, Kennedy CC, Karampatos S, et alMeasuring frailty in clinical practice: a comparison of physical frailty assessment methods in a geriatric out-patient clinic. BMC Geriatr. 2017;17:264.
3. Studenski S, Hayes RP, Leibowitz RQ, et alClinical global impression of change in physical frailty: development of a measure based on clinical judgment. J Am Geriatr Soc. 2004;52:1560–1566.
4. Garonzik-Wang JM, Govindan P, Grinnan JW, et alFrailty and delayed graft function in kidney transplant recipients. Arch Surg. 2012;147:190–193.
5. McAdams-DeMarco MA, Law A, King E, et alFrailty and mortality in kidney transplant recipients. Am J Transplant. 2015;15:149–154.
6. Lynch RJ, Zhang R, Patzer RE, et alFirst-year waitlist hospitalization and subsequent waitlist and transplant outcome. Am J Transplant. 2017;17:1031–1041.
7. Plantinga LC, Lynch RJ, Patzer RE, et alAssociation of Serious Fall Injuries among United States end stage kidney disease patients with access to kidney transplantation. Clin J Am Soc Nephrol. 2018;13:628–637.
8. McAdams-DeMarco MA, Law A, Salter ML, et alFrailty and early hospital readmission after kidney transplantation. Am J Transplant. 2013;13:2091–2095.
9. Lynch RJ, Patzer RE, Pastan SO, et alRecent history of serious fall injuries and posttransplant outcomes among U.S. kidney transplant recipients. Transplantation. 2018; in press.
10. Fried LP, Tangen CM, Walston J, et alFrailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–M156.