Frailty and Long-Term Post-Kidney Transplant Outcomes

  • Mara A. McAdams-DeMarcoEmail author
  • Nadia M. Chu
  • Dorry L. Segev
Frailty and Gerontology (M McAdams-Demarco, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Frailty and Gerontology


Purpose of Review

To highlight recent research about frailty and its role as a predictor of adverse, long-term post-kidney transplant (KT) outcomes.

Recent Findings

Frailty is easily measured using the physical frailty phenotype (PFP) developed by gerontologist Dr. Linda Fried and colleagues. In recent studies, > 50% of KT recipients were frail (20%) or intermediately frail (32%) at KT admission. Frail recipients were at 1.3-times higher risk of immunosuppression intolerance and 2.2-times higher risk of mortality, even after accounting for recipient, donor, and transplant factors; these findings were consistent with those on short-term post-KT outcomes. Pilot data suggests that prehabilitation may be an intervention that increases physiologic reserve in frail KT recipients.


PFP is an effective tool to measure frailty in ESRD that improves risk stratification for short-term and long-term post-KT outcomes. Interventions to improve physiologic reserve and prevent adverse KT outcomes, particularly among frail KT recipients, are needed.


Frailty Kidney transplantation Epidemiology 



This study was supported by the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) grant numbers: R01DK114074 (PI: McAdams-DeMarco), K24DK101828 (PI: Segev), and the National Institute on Aging (NIA) grant numbers: R01AG042504 (PI: Segev), K01AG043501 (PI: McAdams-DeMarco), and R01AG055781 (PI: McAdams-DeMarco). Mara A. McAdams-DeMarco was also supported by the Johns Hopkins University Claude D. Pepper Older Americans Independence Center (P30AG021334).

Compliance with Ethical Standards

Conflict of Interest

Mara McAdams-DeMarco, Nadia Chu, and Dorry Segev declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    McAdams-DeMarco MA, James N, Salter ML, Walston J, Segev DL. Trends in kidney transplant outcomes in older adults. J Am Geriatr Soc. 2014;62(12):2235.PubMedPubMedCentralGoogle Scholar
  2. 2.
    McAdams-Demarco MA, Grams ME, Hall EC, Coresh J, Segev DL. Early hospital readmission after kidney transplantation: patient and center-level associations. Am J Transplant. 2012;12(12):3283–8.CrossRefGoogle Scholar
  3. 3.
    McAdams-DeMarco MA, Bae S, Chu N, et al. Dementia and Alzheimer’s disease among older kidney transplant recipients. J Am Soc Nephrol. 2016.Google Scholar
  4. 4.
    Salter M, Liu J, Bae S, et al. Fractures and associated graft loss and mortality among older kidney transplant recipients. J Am Geriatr Soc, under revision.Google Scholar
  5. 5.
    Meier-Kriesche HU, Ojo AO, Hanson JA, Kaplan B. Exponentially increased risk of infectious death in older renal transplant recipients. Kidney Int. 2001;59(4):1539–43.CrossRefGoogle Scholar
  6. 6.
    Sprangers B, Nair V, Launay-Vacher V, Riella LV, Jhaveri KD. Risk factors associated with post-kidney transplant malignancies: an article from the Cancer-Kidney International Network. Clin Kidney J. 2018;11(3):315–29.CrossRefGoogle Scholar
  7. 7.
    Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Au R, Kannel WB, et al. The lifetime risk of stroke: estimates from the Framingham study. Stroke. 2006;37(2):345–50.CrossRefGoogle Scholar
  8. 8.
    Bao Y, Dalrymple L, Chertow GM, Kaysen GA, Johansen KL. Frailty, dialysis initiation, and mortality in end-stage renal disease frailty, dialysis initiation, & mortality in ESRD. Arch Intern Med. 2012;1.Google Scholar
  9. 9.
    McAdams-DeMarco MA, Law A, Salter ML, et al. Frailty as a novel predictor of mortality and hospitalization in individuals of all ages undergoing hemodialysis. J Am Geriatr Soc. 2013;61(6):896–901.CrossRefGoogle Scholar
  10. 10.
    Painter P, Kuskowski M. A closer look at frailty in ESRD: getting the measure right. Hemodial Int. 2013;17(1):41–9.CrossRefGoogle Scholar
  11. 11.
    Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–57.CrossRefGoogle Scholar
  12. 12.
    Bandeen-Roche K, Xue QL, Ferrucci L, Walston J, Guralnik JM, Chaves P, et al. Phenotype of frailty: characterization in the women's health and aging studies. J Gerontol A Biol Sci Med Sci. 2006;61(3):262–6.CrossRefGoogle Scholar
  13. 13.
    Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1(3):385–401.CrossRefGoogle Scholar
  14. 14.
    Taylor HL, Jacobs DR, Schucker B, Knudsen J, Leon AS, Debacker G. A questionnaire for the assessment of leisure time physical activities. J Chronic Dis. 1978;31(12):741–55.CrossRefGoogle Scholar
  15. 15.
    McAdams-DeMarco MA, Law A, Tan J, et al. Frailty, mycophenolate reduction, and graft loss in kidney transplant recipients. Transplantation. 2015;99:(4):805–10.Google Scholar
  16. 16.
    McAdams-DeMarco MA, Law A, King E, et al. Frailty and mortality in kidney transplant recipients. Am J Transplant. 2015;15(1):149–54.CrossRefGoogle Scholar
  17. 17.
    Bandeen-Roche K, Seplaki CL, Huang J, Buta B, Kalyani RR, Varadhan R, et al. Frailty in older adults: a nationally representative profile in the United States. J Gerontol A Biol Sci Med Sci. 2015;70(11):1427–34.CrossRefGoogle Scholar
  18. 18.
    Brown JC, Harhay MO, Harhay MN. Appendicular lean mass and mortality among prefrail and frail older adults. J Nutr Health Aging. 2017;21(3):342–5.CrossRefGoogle Scholar
  19. 19.
    Blodgett J, Theou O, Kirkland S, Andreou P, Rockwood K. Frailty in NHANES: comparing the frailty index and phenotype. Arch Gerontol Geriatr. 2015;60(3):464–70.CrossRefGoogle Scholar
  20. 20.
    Eichholzer M, Richard A, Walser-Domjan E, Linseisen J, Rohrmann S. Urinary phytoestrogen levels and frailty in older American women of the National Health and Nutrition Examination Survey (NHANES) 1999-2002: a cross-sectional study. Ann Nutr Metab. 2013;63(4):269–76.CrossRefGoogle Scholar
  21. 21.
    Park SK, Richardson CR, Holleman RG, Larson JL. Frailty in people with COPD, using the National Health and Nutrition Evaluation Survey dataset (2003-2006). Heart Lung. 2013;42(3):163–70.CrossRefGoogle Scholar
  22. 22.
    Eichholzer M, Barbir A, Basaria S, Dobs AS, Feinleib M, Guallar E, et al. Serum sex steroid hormones and frailty in older American men of the third National Health and nutrition examination survey (NHANES III). Aging Male. 2012;15(4):208–15.CrossRefGoogle Scholar
  23. 23.
    Wilhelm-Leen ER, Hall YN, M KT, Chertow GM. Frailty and chronic kidney disease: the Third National Health and Nutrition Evaluation Survey. Am J Med. 2009;122(7):664.CrossRefGoogle Scholar
  24. 24.
    Yao X, Li H, Leng SX. Inflammation and immune system alterations in frailty. Clin Geriatr Med. 2011;27(1):79–87.CrossRefGoogle Scholar
  25. 25.
    Walston J, Fried LP. Frailty and the older man. Med Clin N Am. 1999;83(5):1173–94.CrossRefGoogle Scholar
  26. 26.
    Fried LP, Xue QL, Cappola AR, et al. Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci. 2009;64(10):1049.CrossRefGoogle Scholar
  27. 27.
    Xue QL, Tian J, Fried LP, Kalyani RR, Varadhan R, Walston JD, et al. Physical frailty assessment in older women: can simplification be achieved without loss of syndrome measurement validity? Am J Epidemiol. 2016;183(11):1037–44.CrossRefGoogle Scholar
  28. 28.
    Walston JD. Connecting age-related biological decline to frailty and late-life vulnerability. Nestle Nutr Inst Workshop Ser. 2015;83:1.CrossRefGoogle Scholar
  29. 29.
    Bergman H, Ferrucci L, Guralnik J, Hogan DB, Hummel S, Karunananthan S, et al. Frailty: an emerging research and clinical paradigm–issues and controversies. J Gerontol A Biol Sci Med Sci. 2007;62(7):731–7.CrossRefGoogle Scholar
  30. 30.
    Ferrucci L, Windham BG, Fried LP. Frailty in older persons. Genus. 2005;61(1):39–53.Google Scholar
  31. 31.
    Varadhan R, Chaves PH, Lipsitz LA, et al. Frailty and impaired cardiac autonomic control: new insights from principal components aggregation of traditional heart rate variability indices. J Gerontol A Biol Sci Med Sci. 2009;64(6):682.CrossRefGoogle Scholar
  32. 32.
    Chaves PH, Varadhan R, Lipsitz LA, et al. Physiological complexity underlying heart rate dynamics and frailty status in community-dwelling older women. J Am Geriatr Soc. 2008;56(9):1698–703.CrossRefGoogle Scholar
  33. 33.
    Varadhan R, Walston J, Cappola AR, Carlson MC, Wand GS, Fried LP. Higher levels and blunted diurnal variation of cortisol in frail older women. J Gerontol A Biol Sci Med Sci. 2008;63(2):190–5.CrossRefGoogle Scholar
  34. 34.
    Leng SX, Tian X, Matteini A, Li H, Hughes J, Jain A, et al. IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults. Age Ageing. 2011;40(4):475–81.CrossRefGoogle Scholar
  35. 35.
    Leng SX, Xue QL, Tian J, Walston JD, Fried LP. Inflammation and frailty in older women. J Am Geriatr Soc. 2007;55(6):864–71.CrossRefGoogle Scholar
  36. 36.
    Kalyani RR, Varadhan R, Weiss CO, Fried LP, Cappola AR. Frailty status and altered dynamics of circulating energy metabolism hormones after oral glucose in older women. J Nutr Health Aging. 2012;16(8):679–86.CrossRefGoogle Scholar
  37. 37.
    Weiss CO, Cappola AR, Varadhan R, Fried LP. Resting metabolic rate in old-old women with and without frailty: variability and estimation of energy requirements. J Am Geriatr Soc. 2012;60(9):1695–700.CrossRefGoogle Scholar
  38. 38.
    Kalyani RR, Varadhan R, Weiss CO, Fried LP, Cappola AR. Frailty status and altered glucose-insulin dynamics. J Gerontol A Biol Sci Med Sci. 2012;67(12):1300–6.CrossRefGoogle Scholar
  39. 39.
    Leng S, Chaves P, Koenig K, Walston J. Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc. 2002;50(7):1268–71.CrossRefGoogle Scholar
  40. 40.
    Leng SX, Yang H, Walston JD. Decreased cell proliferation and altered cytokine production in frail older adults. Aging Clin Exp Res. 2004;16(3):249–52.CrossRefGoogle Scholar
  41. 41.
    Buta BJ, Walston JD, Godino JG, Park M, Kalyani RR, Xue QL, et al. Frailty assessment instruments: systematic characterization of the uses and contexts of highly-cited instruments. Ageing Res Rev. 2016;26:53–61.CrossRefGoogle Scholar
  42. 42.
    Adlam T, Ulrich E, Kent M, Malinzak L. Frailty testing pilot study: pros and pitfalls. J Clin Med Res. 2018;10(2):82–7.CrossRefGoogle Scholar
  43. 43.
    Schopmeyer L, El Moumni M, Nieuwenhuijs-Moeke GJ, Berger SP, Bakker SJL, Pol RA. Frailty has a significant influence on postoperative complications after kidney transplantation-a prospective study on short-term outcomes. Transpl Int. 2019;32(1):66–74.CrossRefGoogle Scholar
  44. 44.
    McAdams-DeMarco MA, Ying H, Olorundare I, et al. Individual frailty components and mortality in kidney transplant recipients. Transplantation. 2017;101(9):2216–32.Google Scholar
  45. 45.
    McAdams-DeMarco MA, Isaacs K, Darko L, et al. Changes in frailty after kidney transplantation. J Am Geriatr Soc. 2015;63(10):2152–7.CrossRefGoogle Scholar
  46. 46.
    McAdams-DeMarco MA, Olorundare IO, Ying H, et al. Frailty and post kidney transplant health-related quality of life. Transplantation. 2017.Google Scholar
  47. 47.
    Chu NM, Gross AL, Shaffer A, et al. Frailty and changes in cognitive function after kidney transplantation—failure to recover to baseline levels. Under Review in J Am Soc Nephrol. 2019.Google Scholar
  48. 48.
    Warsame F, Haugen CE, Ying H, Garonzik-Wang JM, Desai NM, Hall RK, et al. Limited health literacy and adverse outcomes among kidney transplant candidates. Am J Transplant. 2018.Google Scholar
  49. 49.
    •• Haugen CE, Mountford A, Warsame F, et al. Incidence, risk factors, and sequelae of post-kidney transplant delirium. J Am Soc Nephrol. 2018;29(6):1752 Frail kidney transplant (KT) recipients are particularly vulnerable to surgical stressors resulting in delirium, an acute decline and fluctuation in cognitive function; 20.0% of frail recipients aged ≥ 75 experienced delirium. These frail recipients with delirium had an increased risk of ≥2 week length of stay, institutional discharge (discharge to skilled nursing facility or rehabilitation center), mortality, and graft loss. CrossRefGoogle Scholar
  50. 50.
    Konel JM, Warsame F, Ying H, et al. Depressive symptoms, frailty, and adverse outcomes among kidney transplant recipients. Clin Transpl. 2018;32(10):e13391.CrossRefGoogle Scholar
  51. 51.
    McAdams-DeMarco MA, King EA, Luo X, et al. Frailty, length of stay, and mortality in kidney transplant recipients: a national registry and prospective cohort study. Ann Surg. 2017;266(6):1084–90.Google Scholar
  52. 52.
    Haugen CE, Mountford A, Warsame F, et al. Incidence, risk factors, and sequelae of post-kidney transplant delirium. J Am Soc Nephrol. 2018;29(6):1752–9.CrossRefGoogle Scholar
  53. 53.
    Garonzik-Wang JM, Govindan P, Grinnan JW, Liu M, Ali HM, Chakraborty A, et al. Frailty and delayed graft function in kidney transplant recipients. Arch Surg. 2012;147(2):190–3.CrossRefGoogle Scholar
  54. 54.
    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.CrossRefGoogle Scholar
  55. 55.
    Michelson AT, Tsapepas DS, Husain SA, Brennan C, Chiles MC, Runge B, et al. Association between the “timed up and go test” at transplant evaluation and outcomes after kidney transplantation. Clin Transpl. 2018;32:e13410.CrossRefGoogle Scholar
  56. 56.
    •• Nastasi AJ, McAdams-DeMarco MA, Schrack J, et al. Pre-Kidney Transplant Lower Extremity Impairment and Post-Kidney Transplant Mortality 2018;18(1):189–196. This study suggests that frailty is distinct from lower extremity impairment. Using the Short Physical Performance Battery identifies a different group of vulnerable KT recipients than the PFP. Google Scholar
  57. 57.
    Nastasi AJ, Bryant TS, Le JT, et al. Pre-kidney transplant lower extremity impairment and transplant length of stay: a time-to-discharge analysis of a prospective cohort study. BMC Geriatr. 2018;18(1):246.Google Scholar
  58. 58.
    Rumer KK, Saraswathula A, Melcher ML. Prehabilitation in our most frail surgical patients: are wearable fitness devices the next frontier? Curr Opin Organ Transplant. 2016;21(2):188–93.CrossRefGoogle Scholar
  59. 59.
    Cheng XS, Myers JN, Chertow GM, et al. Prehabilitation for kidney transplant candidates: is it time? Clin Transplant, 2017. 31(8).Google Scholar
  60. 60.
    • McAdams-DeMarco MA, Ying H, Van Pilsum Rasmussen S, et al. Prehabilitation prior to kidney transplantation: preliminary results from a pilot study. Clin Transpl. 2019. This is the first study of prehabilitation in KT recipients. Frail recipients were able to participate in prehabilitation and prehabilitation was associated with increased physical activity. There was initial evidence that prehabilitation was associated with a decreased length of stay post-KT. Google Scholar
  61. 61.
    Puts MT, Toubasi S, Andrew MK, et al. Interventions to prevent or reduce the level of frailty in community-dwelling older adults: a scoping review of the literature and international policies. Age Ageing. 2017;46(3):383–92.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Myers JN, Fonda H. The impact of fitness on surgical outcomes: the case for prehabilitation. Curr Sports Med Rep. 2016;15(4):282–9.PubMedGoogle Scholar
  63. 63.
    Gillis C, Carli F. Promoting perioperative metabolic and nutritional care. Anesthesiology. 2015;123(6):1455–72.CrossRefGoogle Scholar
  64. 64.
    Gillis C, Loiselle SE, Fiore JF, Jr., et al. Prehabilitation with whey protein supplementation on perioperative functional exercise capacity in patients undergoing colorectal resection for cancer: a pilot double-blinded randomized placebo-controlled trial. J Acad Nutr Diet. 2016;116(5):802–12.Google Scholar
  65. 65.
    Gillis C, Loiselle SE, Fiore JF Jr, Awasthi R, Wykes L, Liberman AS, et al. Prehabilitation with whey protein supplementation on perioperative functional exercise capacity in patients undergoing colorectal resection for cancer: a pilot double-blinded randomized placebo-controlled trial. J Acad Nutr Diet. 2016;116(5):802–12.CrossRefGoogle Scholar
  66. 66.
    Tsimopoulou I, Pasquali S, Howard R, et al. Psychological prehabilitation before cancer surgery: a systematic review. Ann Surg Oncol. 2015;22(13):4117–23.CrossRefGoogle Scholar
  67. 67.
    Van Pilsum RS, Konel J, Warsame F, et al. Engaging clinicians and patients to assess and improve frailty measurement in adults with end stage renal disease. BMC Nephrol. 2018;19(1):8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Mara A. McAdams-DeMarco
    • 1
    • 2
    Email author
  • Nadia M. Chu
    • 1
    • 2
  • Dorry L. Segev
    • 1
    • 2
  1. 1.Department of SurgeryJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of EpidemiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA

Personalised recommendations