Frailty in the context of kidney transplantation

Sandes-Freitas, Tainá Veras de; Domingues-da-Silva, Raoni de Oliveira; Sanders-Pinheiro, Helady

doi:10.1590/2175-8239-JBN-2024-0048en

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Brasil

Brazilian Journal of Nephrology

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Brasil

Español English

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Review Article • Braz. J. Nephrol. 46 (4) • Oct-Dec 2024 • https://doi.org/10.1590/2175-8239-JBN-2024-0048en copy

Frailty in the context of kidney transplantation

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Frailty, defined as an inappropriate response to stressful situations due to the loss of physiological reserve, was initially described in the elderly population, but is currently being identified in younger populations with chronic diseases, such as chronic kidney disease. It is estimated that about 20% of patients are frail at the time of kidney transplantation (KT), and there is great interest in its potential predictive value for unfavorable outcomes. A significant body of evidence has been generated; however, several areas still remain to be further explored. The pathogenesis is poorly understood and limited to the extrapolation of findings from other populations. Most studies are observational, involving patients on the waiting list or post-KT, and there is a scarcity of data on long-term evolution and possible interventions. We reviewed studies, including those with Brazilian populations, assessing frailty in the pre- and post-KT phases, exploring pathophysiology, associated factors, diagnostic challenges, and associated outcomes, in an attempt to provide a basis for future interventions.

Keywords:
Frailty; Kidney Transplant; Chronic Kidney Disease; Incidence; Risk Factors; Access to Health Services

Tool	Author(s)	Domains Assessed	Advantages	Disadvantages
Instruments for Assessing the Physical Frailty Phenotype
Fried Frailty Scale	Fried et al.²⁴24. 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):56. doi: http://doi.org/10.1093/gerona/56.3.M146. PubMed PMID: 11253156. https://doi.org/10.1093/gerona/56.3.M146... (Cardiovascular Health Study, Johns Hopkins Medical Institutions – USA)	Muscle weakness (handgrip strength) Exhaustion Unintentional weight loss Physical inactivity Slow gait	Practical and easy to apply. Extensively validated in KT cohorts. Validated and/or cross-culturally adapted²⁵25. Lustosa LP, Pereira DS, Dias RC, Britto RR, Parentoni AN, Pereira LSM. Translation and cultural adaptation of the Minnesota Leisure Time Activities Questionnaire in community-dwelling older people. Geriatr Gerontol Aging. 2011;5(2):57–65.,²⁶26. Tavares Batistoni SS, Neri AL, Bretas Cupertino APF. Validade da escala de depressão do Center for Epidemiological Studies entre idosos brasileiros. Rev Saude Publica. 2007;41(4):598–605. doi: http://doi.org/10.1590/S0034-89102007000400014. https://doi.org/10.1590/S0034-8910200700... .	Requires a dynamometer. Exhaustion may be subjective (self-reported). Physical inactivity may be subjective (self-reported). Limited for patients with motor deficits.
Short Physical Performance Battery (SPPB)	Welch et al.²⁷27. Welch SA, Ward RE, Beauchamp MK, Leveille SG, Travison T, Bean JF. The Short Physical Performance Battery (SPPB): A Quick and Useful Tool for Fall Risk Stratification Among Older Primary Care Patients. J Am Med Dir Assoc. 2021;22(8):1646–51. doi: http://doi.org/10.1016/j.jamda.2020.09.038. PubMed PMID: 33191134. https://doi.org/10.1016/j.jamda.2020.09.... (Vanderbilt University Medical Center – USA)	Slow gait Balance Muscle weakness (lower limbs)	Practical and easy to apply. Validated and/or cross-culturally adapted²⁸28. Rocco LLG, Fernandes TG. Validity of the short physical performance battery for screening for frailty syndrome among older people in the Brazilian Amazon region. A cross-sectional study. Sao Paulo Med J. 2020;138(6):537–44. doi: http://doi.org/10.1590/1516-3180.2020.0264.r1.14092020. PubMed PMID: 33263707. https://doi.org/10.1590/1516-3180.2020.0... .	Limited to patients with conditions affecting only lower limbs.
Instruments Based on the Accumulation of Deficits Model
Edmonton Frail Scale	Rolfson et al.²⁹29. Rolfson D, Majumdar SR, Taher A, Tsuyuki R. Development and validation of a new instrument for frailty. Clin Invest Med. 2000;23. (University of Alberta – Canada)	Domains related to factors such as cognition, general health status, functional independence, and social support.	It is increasingly used in hospital practice, with adaptations for emergencies in the elderly³⁰30. Hilmer SN, Perera V, Mitchell S, Murnion BP, Dent J, Bajorek B, et al. The assessment of frailty in older people in acute care. Australas J Ageing. 2009;28(4):182–8. doi: http://doi.org/10.1111/j.1741-6612.2009.00367.x. PubMed PMID: 19951339. https://doi.org/10.1111/j.1741-6612.2009... . Validated and/or cross-culturally adapted³¹31. Fabrício-Wehbe SCC, Schiaveto FV, Vendrusculo TRP, Haas VJ, Dantas RAS, Rodrigues RAP. Cross-cultural adaptation and validity of the «Edmonton Frail Scale – EFS» in a Brazilian elderly sample. Rev Lat Am Enfermagem. 2009;17(6):1043–9. doi: http://doi.org/10.1590/S0104-11692009000600018. PubMed PMID: 20126949. https://doi.org/10.1590/S0104-1169200900... .	It includes subjective questions. Assessment of complex domains such as cognition, depression, and physical performance in a single question may not accurately capture the patient’s condition.
Groningen Frailty Index	Steverink et al.³²32. Steverink N, Slaets J, Schuurmans H, Lis M. Measuring frailty: developing and testing the GFI (Groningen Frailty Indicator). Gerontologist. 2001;41:236–7. (University of Groningen – Netherlands)	Domains related to mobility, vision, hearing, nutrition, comorbidities, cognition, psychosocial, and physical capacity.	Binary answers facilitate the test application. Widely used in the Netherlands, in conjunction with the Frailty Index. Validated and/or cross-culturally adapted³³33. Lira Borges C, Karen B, Fernandes C, Wilker J, Clares B, Lígia M, et al. Tradução e adaptação transcultural do Groningen Frailty Indicator para idosos brasileiros. J Health Biol Sci. 2019;7(3):242–7. doi: http://doi.org/10.12662/2317-3076jhbs.v7i3.2230.p242-247.2019. https://doi.org/10.12662/2317-3076jhbs.v... .	Binary answers may not properly capture the conditions. More extensive and complex, difficult to apply in the context of KT.
Tilburg Frailty Indicator	Gobbens et al.³⁴34. Gobbens RJJ, van Assen MALM, Luijkx KG, Wijnen-Sponselee MT, Schols JMGA. The tilburg frailty indicator: psychometric properties. J Am Med Dir Assoc. 2010;11(5):344–55. doi: http://doi.org/10.1016/j.jamda.2009.11.003. PubMed PMID: 20511102. https://doi.org/10.1016/j.jamda.2009.11.... (Tilburg University – Netherlands)	Physical, psychological, and social domains through several questionnaires, such as: LASA Physical Activity Questionnaire, Timed Up & Go test, Loneliness Scale, and Social Support List, among others.	Physical components with good predictive value. Validated and/or cross-culturally adapted³⁵35. Santiago LM, Luz LL, Mattos IE, Gobbens RJJ. Adaptação transcultural do instrumento Tilburg Frailty Indicator (TFI) para a população brasileira. Cad Saude Publica. 2012;28(9):1795–801. doi: http://doi.org/10.1590/S0102-311X2012000900018. PubMed PMID: 23033194. https://doi.org/10.1590/S0102-311X201200... .	Social components with low predictive value³⁴34. Gobbens RJJ, van Assen MALM, Luijkx KG, Wijnen-Sponselee MT, Schols JMGA. The tilburg frailty indicator: psychometric properties. J Am Med Dir Assoc. 2010;11(5):344–55. doi: http://doi.org/10.1016/j.jamda.2009.11.003. PubMed PMID: 20511102. https://doi.org/10.1016/j.jamda.2009.11.... . More extensive and complex, difficult to apply in the context of KT.
Kihon Checklist	Arai and Satake³⁶36. Arai H, Satake S. English translation of the Kihon Checklist. Geriatr Gerontol Int. 2015;15(4):518–9. doi: http://doi.org/10.1111/ggi.12397. PubMed PMID: 25828791. https://doi.org/10.1111/ggi.12397... (Care Prevention Programs – Japan)	Domains related to ADL, physical functionality, weight, appetite, mood, memory and willingness to perform activities through a questionnaire with 25 binary questions.	Binary answers facilitate the test application. Widely used in Japan. Validated and/or cross-culturally adapted³⁷37. Sewo Sampaio PY, Sampaio RAC, Yamada M, Ogita M, Arai H. Validation and translation of the Kihon Checklist (frailty index) into Brazilian Portuguese. Geriatr Gerontol Int. 2014;14(3):561–9. doi: http://doi.org/10.1111/ggi.12134. PubMed PMID: 23992357. https://doi.org/10.1111/ggi.12134... .	Binary answers may not properly capture the conditions.
Clinical Frailty Scale	Rockwood et al.¹¹ (Geriatric Medicine Dalhousie University – Canada)	Assesses cognitive and physical domains, dependence on ADLs and IADLs, and the CSHA Frailty Index	Good outcome predictor in hospitalized elderly patients³⁸38. Basic D, Shanley C. Frailty in an older inpatient population: using the clinical frailty scale to predict patient outcomes. J Aging Health. 2015;27(4):670–85. doi: http://doi.org/10.1177/0898264314558202. PubMed PMID: 25414168. https://doi.org/10.1177/0898264314558202... . Validated and/or cross-culturally adapted³⁹39. Rodrigues MK, Nunes Rodrigues I, Vasconcelos Gomes da Silva DJ, De JM, Oliveira MF. Clinical Frailty Scale: Translation and Cultural Adaptation Into the Brazilian Portuguese Language. J Frailty Aging. 2021;10(1):38–43. PubMed PMID: 33331620..	Being based on clinical judgment, it is subject to the evaluator’s subjectivity. More extensive and complex, difficult to apply in the context of KT.
Easycare Two-step Older Persons Screening (Easycare-TOS)	Van Kempen et al.⁴⁰ (Radboud University Nijmegen Medical Centre – Netherlands)	14 domains: multimorbidity, polypharmacy, cognitive impairment, hearing and vision, ADL, mobility, falls, self-care, social support, depression, anxiety, somatic complaints, psychiatric complaints.	Used in primary care as a practical assessment tool.	Subjectivity of the evaluator, rather than a numerical score to certify frailty, increases variability. Two-stage assessment increases the need for time and personnel. Non-validated and/or lacking cross-cultural adaptation in Brazil. To date, there are no studies that have used this tool in KT recipients.
Clinical-Functional Vulnerability Index-20 (IVCF-20)	de Moraes et al.⁴¹41. de Moraes EN, do Carmo JA, de Moraes FL, Azevedo RS, Machado CJ, Montilla DER. Clinical-Functional Vulnerability Index-20 (IVCF-20): rapid recognition of frail older adults. Rev Saude Publica. 2016;50:81. doi: http://doi.org/10.1590/s1518-8787.2016050006963. PubMed PMID: 28099667. https://doi.org/10.1590/s1518-8787.20160... (Universidade Federal de Minas Gerais – Brazil)	8 domains: age, self-perceived health, functional disabilities, cognition, mood, mobility, communication, and multiple comorbidities.	Proposed as a tool for rapid screening of vulnerability in Brazilian elderly.	Applied and validated in elderly population and specialized hospital care. To date, there are no studies that have used this tool in KT recipients.
Canadian Study of Health and Aging (CSHA) Frailty Index	Mitnitski et al.⁴²42. Mitnitski AB, Mogilner AJ, Rockwood K. Accumulation of deficits as a proxy measure of aging. ScientificWorldJournal. 2001;1:323–36. doi: http://doi.org/10.1100/tsw.2001.58. PubMed PMID: 12806071. https://doi.org/10.1100/tsw.2001.58... (Ecole Polytechnique – Canada)	Domains related to 70 health deficits, including comorbidities, dependence on ADLs and IADLs, cognitive impairment, slow gait, depression, etc.	Flexible, due to the possibility of adapting the instrument based on the studied population. Good outcome predictor⁴³43. Theou O, Brothers TD, Mitnitski A, Rockwood K. Operationalization of frailty using eight commonly used scales and comparison of their ability to predict all-cause mortality. J Am Geriatr Soc. 2013;61(9):1537–51. doi: http://doi.org/10.1111/jgs.12420. PubMed PMID: 24028357. https://doi.org/10.1111/jgs.12420... .	Extensive and complex, difficult to apply in the context of KT. Calculations required. Non-validated and/or lacking cross-cultural adaptation in Brazil. To date, there are no studies that have used this tool in KT recipients.

First author	Year	Country	Sample size	Assessment tool	Age (years, mean ± SD or median, min-max)	Female (%)	Frailty (%)
Assessment Conducted in Patients on the Waiting List for KT
Chen X⁴⁶46. Chen X, Chu NM, Thompson V, Quint EE, Alasfar S, Xue QL, et al. Development and Validation of an Abridged Physical Frailty Phenotype for Clinical Use: A Cohort Study Among Kidney Transplant Candidates. J Gerontol A Biol Sci Med Sci. 2024;79(1):79. doi: http://doi.org/10.1093/gerona/glad173. PubMed PMID: 37466327. https://doi.org/10.1093/gerona/glad173...	2024	USA	220	FFP	–	–	23.8
Xu EJ⁶³63. Xu EJ, Kyriazis P, Pawar A, Pavlakis M, Aala A. Frailty and kidney transplant waitlisting: a single-center experience. Transplant Proc. 2024;56(1):37–43. doi: http://doi.org/10.1016/j.transproceed.2023.10.009. PubMed PMID: 38195285. https://doi.org/10.1016/j.transproceed.2...	2024	USA	101	SPPB and GFI	53.3 ± 12.0	35.6	39.6
Thind AK⁶⁴64. Thind AK, Levy S, Wellsted D, Willicombe M, Brown EA. Frailty and the psychosocial components of the edmonton frail scale are most associated with patient experience in older kidney transplant candidates – a secondary analysis within the kidney transplantation in older people (KTOP) study. Front Neurol. 2023;2:1058765. doi: http://doi.org/10.3389/fneph.2022.1058765. PubMed PMID: 37675015. https://doi.org/10.3389/fneph.2022.10587...	2023	England	186	EFS	66.0/65.1/64.6^a	33.9/27.8/46.9^b	17.2
Schaenman J⁶⁵65. Schaenman J, Ahn R, Lee C, Hale-Durbin B, Abdalla B, Danovitch G, et al. Physical frailty predicts outcomes in patients undergoing evaluation for kidney transplantation. Transplant Proc. 2023;55(10):2372–7. doi: http://doi.org/10.1016/j.transproceed.2023.09.033. PubMed PMID: 37985351. https://doi.org/10.1016/j.transproceed.2...	2023	USA	514	SPPB/FFP	64 (55–84)	37.0	23.0/8.0^c
1408	SPPB/FFP	64 (55–84)	37.0	18.0/6.0^c
Pérez-Sáez MJ⁶⁶66. Pérez-Sáez MJ, Arias-Cabrales CE, Redondo-Pachón D, Burballa C, Buxeda A, Bach A, et al. Increased mortality after kidney transplantation in mildly frail recipients. Clin Kidney J. 2022;15(11):2089–96. doi: http://doi.org/10.1093/ckj/sfac159. PubMed PMID: 36325004. https://doi.org/10.1093/ckj/sfac159...	2022	Spain	296	FFP	62.6 ± 12.3	29.4	26.7
Pérez-Sáez MJ⁶⁷67. Pérez-Sáez MJ, Dávalos-Yerovi V, Redondo-Pachón D, Arias-Cabrales CE, Faura A, Bach A, et al. Frailty in kidney transplant candidates: a comparison between physical frailty phenotype and FRAIL scales. J Nephrol. 2022;35(7):1841–9. doi: http://doi.org/10.1007/s40620-021-01234-4. PubMed PMID: 34978704. https://doi.org/10.1007/s40620-021-01234...	2022	Spain	451	FFP	60.9 ± 12.2	31.7	10.4
Chen X⁶⁸68. Chen X, Shafaat O, Liu Y, King EA, Weiss CR, Xue QL, et al. Revision of frailty assessment in kidney transplant recipients: replacing unintentional weight loss with CT-assessed sarcopenia in the physical frailty phenotype. Am J Transplant. 2022;22(4):1145–57. doi: http://doi.org/10.1111/ajt.16934. PubMed PMID: 34953170. https://doi.org/10.1111/ajt.16934...	2022	USA	1113	FFP	52.9 ± 13.8	38.6	18.6
Pérez-Sáez MJ²¹21. Pérez-Sáez MJ, Arias-Cabrales CE, Dávalos-Yerovi V, Redondo D, Faura A, Vera M, et al. Frailty among chronic kidney disease patients on the kidney transplant waiting list: the sex-frailty paradox. Clin Kidney J. 2021;15(1):109–18. doi: http://doi.org/10.1093/ckj/sfab133. PubMed PMID: 35035941. https://doi.org/10.1093/ckj/sfab133...	2021	Spain	455	FFP	60.6 ± 12.4	31.6	10.3
Haugen CE⁶⁹69. Haugen CE, Gross A, Chu NM, Norman SP, Brennan DC, Xue QL, et al. Development and validation of an inflammatory-frailty index for kidney transplantation. J Gerontol A Biol Sci Med Sci. 2021;76(3):470–7. doi: http://doi.org/10.1093/gerona/glaa167. PubMed PMID: 32619229. https://doi.org/10.1093/gerona/glaa167...	2021	USA	1154	FFP	54.0 ± 13.0	34.3	19.0
Worthen G⁷⁰70. Worthen G, Vinson A, Cardinal H, Doucette S, Gogan N, Gunaratnam L, et al. Prevalence of frailty in patients referred to the kidney transplant waitlist. Kidney360. 2021;2(8):1287–95. doi: http://doi.org/10.34067/KID.0001892021. PubMed PMID: 35369656. https://doi.org/10.34067/KID.0001892021...	2021	USA	542	FFP	54.0 ± 14.0	36.0	16.2
Chu NM⁷¹71. Chu NM, Chen X, Norman SP, Fitzpatrick J, Sozio SM, Jaar BG, et al. Frailty prevalence in younger end-stage kidney disease patients undergoing dialysis and transplantation. Am J Nephrol. 2020;51(7):501–10. doi: http://doi.org/10.1159/000508576. PubMed PMID: 32640462. https://doi.org/10.1159/000508576...	2020	USA	4304	FFP	55.3 ± 14.8	40.8	12.3
Chu NM⁷²72. Chu NM, Shi Z, Berkowitz R, Haugen CE, Garonzik-Wang J, Norman SP, et al. Poor outcomes in kidney transplant candidates and recipients with history of falls. Transplantation. 2020;104(8):1738–45. doi: http://doi.org/10.1097/TP.0000000000003057. PubMed PMID: 32732854. https://doi.org/10.1097/TP.0000000000003...	2020	USA	3666	FFP	54.0 ± 14.0	38.1	20.9
Haugen CE⁷³73. Haugen CE, Agoons D, Chu NM, Liyanage L, Long J, Desai NM, et al. Physical impairment and access to kidney transplantation. Transplantation. 2020;104(2):367–73. doi: http://doi.org/10.1097/TP.0000000000002778. PubMed PMID: 31033648. https://doi.org/10.1097/TP.0000000000002...	2020	USA	3143	FFP	54.0 ± 14.0	40.0	57.9
Pérez Fernandéz M⁵³53. Pérez Fernández M, Martínez Miguel P, Ying H, Haugen CE, Chu NM, Rodríguez Puyol DM, et al. Comorbidity, frailty, and waitlist mortality among kidney transplant candidates of all ages. Am J Nephrol. 2019;49(2):103–10. doi: http://doi.org/10.1159/000496061. PubMed PMID: 30625489. https://doi.org/10.1159/000496061...	2019	USA	2086	FFP	53.8 ± 13.5	40.1	18.1
Haugen CE⁵⁴54. Haugen CE, Chu NM, Ying H, Warsame F, Holscher CM, Desai NM, et al. Frailty and access to kidney transplantation. Clin J Am Soc Nephrol. 2019;14(4):576–82. doi: http://doi.org/10.2215/CJN.12921118. PubMed PMID: 30890577. https://doi.org/10.2215/CJN.12921118...	2019	USA	4552	FFP	52.0 ± 13.0	61.0	12.3
Lorenz EC⁷⁴74. Lorenz EC, Cosio FG, Bernard SL, Bogard SD, Bjerke BR, Geissler EN, et al. The relationship between frailty and decreased physical performance with death on the kidney transplant waiting list. Prog Transplant. 2019;29(2):108–14. doi: http://doi.org/10.1177/1526924819835803. PubMed PMID: 30879429. https://doi.org/10.1177/1526924819835803...	2019	USA	272	FFP	61.8 ± 9.3	37.9	14.3
Shrestha P⁷⁵75. Shrestha P, Haugen CE, Chu NM, Shaffer A, Garonzik-Wang J, Norman SP, et al. Racial differences in inflammation and outcomes of aging among kidney transplant candidates. BMC Nephrol. 2019;20(1):176. doi: http://doi.org/10.1186/s12882-019-1360-8. PubMed PMID: 31101015. https://doi.org/10.1186/s12882-019-1360-...	2019	USA	1003	FFP	55.0 ± 13.0	40.0	19.1
Vera Casanova⁷⁶76. Vera Casanova M, Bach Pascual A, Martínez Sáez A, Castillo Piña Y, Faura Vendrell A, Redondo Pachón D. Fragilidad y estado nutricional en el periodo pre-trasplante. ¿Existe relación? Enfermería Nefrológica. 2017;20(3):227–32. doi: http://doi.org/10.4321/S2254-28842017000300005. https://doi.org/10.4321/S2254-2884201700...	2017	Spain	177	FFP	62.1 ± 10.4	40.1	31.1^d
Assessment Conducted at the Time of Admission for KT
Parajuli S⁷⁷77. Parajuli S, Astor BC, Lorden HM, O’Toole KA, Wallschlaeger RE, Breyer IC, et al. Analysis of individual components of frailty: pre-transplant grip strength is the strongest predictor of post kidney transplant outcomes. Clin Transplant. 2022;36(12):e14827. doi: http://doi.org/10.1111/ctr.14827. PubMed PMID: 36166355. https://doi.org/10.1111/ctr.14827...	2022	USA	825	FFP	55.3^e	40.0	11.5
Haugen CE⁶⁹69. Haugen CE, Gross A, Chu NM, Norman SP, Brennan DC, Xue QL, et al. Development and validation of an inflammatory-frailty index for kidney transplantation. J Gerontol A Biol Sci Med Sci. 2021;76(3):470–7. doi: http://doi.org/10.1093/gerona/glaa167. PubMed PMID: 32619229. https://doi.org/10.1093/gerona/glaa167...	2021	USA	378	FFP	54.0 ± 13.0	34.3	19.0
Dos Santos Mantovani M⁵⁷57. dos Santos Mantovani M, de Carvalho NC, Archangelo TE, de Andrade LGM, Ferreira Fo SP, de Souza Cavalcante R, et al. Frailty predicts surgical complications after kidney transplantation. A propensity score matched study. PLoS One. 2020;15(2):e0229531. doi: http://doi.org/10.1371/journal.pone.0229531. PubMed PMID: 32102091. https://doi.org/10.1371/journal.pone.022...	2020	Brazil	87	FFP	44.0 ± 12.0/ 46.0 ± 13.0^f	41.4	16.1
Haugen CE⁷⁸78. Haugen CE, Thomas AG, Chu NM, Shaffer AA, Norman SP, Bingaman AW, et al. Prevalence of Frailty among Kidney Transplant Candidates and Recipients in the United States: Estimates from a National Registry and Multi-center Cohort Study. Am J Transplant. 2020;20(4):1170–80. doi: http://doi.org/10.1111/ajt.15709. PubMed PMID: 31733176. https://doi.org/10.1111/ajt.15709...	2020	USA	4616	FFP	52.2 ± 13.4	45.7	13.3
Kosoku A⁷⁹79. Kosoku A, Uchida J, Iwai T, Shimada H, Kabei K, Nishide S, et al. Frailty is associated with dialysis duration before transplantation in kidney transplant recipients: a Japanese single-center cross-sectional study. Int J Urol. 2020;27(5):408–14. doi: http://doi.org/10.1111/iju.14208. PubMed PMID: 32145708. https://doi.org/10.1111/iju.14208...	2020	Japan	205	KCL	55.0 (45.0–65.0)	43.0	11.2
Thomas AG⁸⁰80. Thomas AG, Ruck JM, Chu NM, Agoons D, Shaffer AA, Haugen CE, et al. Kidney transplant outcomes in recipients with visual, hearing, physical and walking impairments: a prospective cohort study. Nephrol Dial Transplant. 2020;35(7):1262–70. doi: http://doi.org/10.1093/ndt/gfz164. PubMed PMID: 31411724. https://doi.org/10.1093/ndt/gfz164...	2020	USA	465	FFP	52.6 ± 15.6	37.2	13.3
Chu NM⁵⁵55. Chu NM, Deng A, Ying H, Haugen CE, Garonzik Wang JM, Segev DL, et al. Dynamic frailty before kidney transplantation: time of measurement matters. Transplantation. 2019;103(8):1700–4. doi: http://doi.org/10.1097/TP.0000000000002563. PubMed PMID: 31348438. https://doi.org/10.1097/TP.0000000000002...	2019	USA	569	FFP	51.7 ± 14.0	39.2	16.0
Chu NM⁸¹81. Chu NM, Gross AL, Shaffer AA, Haugen CE, Norman SP, Xue QL, et al. Frailty and changes in cognitive function after kidney transplantation. J Am Soc Nephrol. 2019;30(2):336–45. doi: http://doi.org/10.1681/ASN.2018070726. PubMed PMID: 30679381. https://doi.org/10.1681/ASN.2018070726...	2019	USA	665	FFP	52.0 ± 14.2	38.8	15.0
Schopmeyer L⁸²82. 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. doi: http://doi.org/10.1111/tri.13330. PubMed PMID: 30099780. https://doi.org/10.1111/tri.13330...	2019	Netherlands	139	GFI	51.8 ± 14.5	37.4	16.5
Thomas AG⁸³83. Thomas AG, Ruck JM, Shaffer AA, Haugen CE, Ying H, Warsame F, et al. Kidney transplant outcomes in recipients with cognitive impairment: a national registry and prospective cohort study. Transplantation. 2019;103(7):1504–13. doi: http://doi.org/10.1097/TP.0000000000002431. PubMed PMID: 30153224. https://doi.org/10.1097/TP.0000000000002...	2019	USA	864	FFP	53.0 ± 3.3	38.4	16.7
Haugen CE⁸⁴84. Haugen CE, Mountford A, Warsame F, Berkowitz R, Bae S, Thomas AG, et al. Incidence, risk factors, and sequelae of post-kidney transplant delirium. J Am Soc Nephrol. 2018;29(6):1752–9. doi: http://doi.org/10.1681/ASN.2018010064. PubMed PMID: 29685884. https://doi.org/10.1681/ASN.2018010064...	2018	USA	893	FFP	52.5 ± 14.2	39.0	16.4
Konel JM⁸⁵85. Konel JM, Warsame F, Ying H, Haugen CE, Mountford A, Chu NM, et al. Depressive symptoms, frailty, and adverse outcomes among kidney transplant recipients HHS Public Access. Clin Transplant. 2018;32(10):e13391. doi: http://doi.org/10.1111/ctr.13391. https://doi.org/10.1111/ctr.13391...	2018	USA	773	FFP	54.0 ± 14.0	37.8	16.3
McAdams-DeMarco MA⁸⁶86. McAdams-DeMarco MA, Olorundare IO, Ying H, Warsame F, Haugen CE, Hall R, et al. Frailty and postkidney transplant health-related quality of life. Transplantation. 2018;102(2):291–9. doi: http://doi.org/10.1097/TP.0000000000001943. PubMed PMID: 28885489. https://doi.org/10.1097/TP.0000000000001...	2018	USA	443	FFP	52.0 ± 14.1	37.3	37.0^d
Nastasi AJ⁸⁷87. Nastasi AJ, McAdams-DeMarco MA, Schrack J, Ying H, Olorundare I, Warsame F, et al. Pre-kidney transplant lower extremity impairment and post-transplant mortality. Am J Transplant. 2018;18(1):189–96. doi: http://doi.org/10.1111/ajt.14430. PubMed PMID: 28710900. https://doi.org/10.1111/ajt.14430...	2018	USA	719	FFP	51.6 ± 14.2	37.7	15.7
McAdams-DeMarco MA⁸⁸88. McAdams-DeMarco MA, Ying H, Olorundare I, King EA, Haugen C, Buta B, et al. Individual frailty components and mortality in kidney transplant recipients. Transplantation. 2017;101(9):2126–32. doi: http://doi.org/10.1097/TP.0000000000001546. PubMed PMID: 27779573. https://doi.org/10.1097/TP.0000000000001...	2017	USA	663	FFP	53.0 ± 13.9	38.0	19.5
McAdams-DeMarco MA⁸⁹89. McAdams-DeMarco MA, Law A, King E, Orandi B, Salter M, Gupta N, et al. Frailty and mortality in kidney transplant recipients. Am J Transplant. 2015;15(1):149–54. doi: http://doi.org/10.1111/ajt.12992. PubMed PMID: 25359393. https://doi.org/10.1111/ajt.12992...	2015	USA	537	FFP	53.0 ± 14.0	39.9	19.9
McAdams-DeMarco MA⁶²62. McAdams-DeMarco MA, Law A, Tan J, Delp C, King EA, Orandi B, et al. Frailty, mycophenolate reduction, and graft loss in kidney transplant recipients. Transplantation. 2015;99(4):805–10. doi: http://doi.org/10.1097/TP.0000000000000444. PubMed PMID: 25393156. https://doi.org/10.1097/TP.0000000000000...	2015	USA	525	FFP	53.0 ± 14.0	39.8	19.5
McAdams-DeMarco MA⁵⁸58. McAdams-DeMarco MA, Isaacs K, Darko L, Salter ML, Gupta N, King EA, et al. Changes in Frailty After Kidney Transplantation. J Am Geriatr Soc. 2015;63(10):2152–7. doi: http://doi.org/10.1111/jgs.13657. PubMed PMID: 26416770. https://doi.org/10.1111/jgs.13657...	2015	USA	349	FFP	53.3 ± 14.2	38.1	19.8
McAdams-DeMarco MA⁹⁰90. McAdams-DeMarco MA, Law A, Salter ML, Chow E, Grams M, Walston J, et al. Frailty and early hospital readmission after kidney transplantation. Am J Transplant. 2013;13(8):2091–5. doi: http://doi.org/10.1111/ajt.12300. PubMed PMID: 23731461. https://doi.org/10.1111/ajt.12300...	2013	USA	383	FFP	53.5 ± 13.9	39.7	18.8
Garonzik-Wang JM⁹¹91. 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. doi: http://doi.org/10.1001/archsurg.2011.1229. PubMed PMID: 22351919. https://doi.org/10.1001/archsurg.2011.12...	2012	USA	183	FFP	53.0 ± 14.0	36.0	25.1

Sociedade Brasileira de Nefrologia Rua Machado Bittencourt, 205 - 5ºandar - conj. 53 - Vila Clementino - CEP:04044-000 - São Paulo SP, Telefones: (11) 5579-1242/5579-6937, Fax (11) 5573-6000 - São Paulo - SP - Brazil
E-mail: bjnephrology@gmail.com

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[1] Correspondence to: Helady Sanders-Pinheiro. Email: heladysanders@gmail.com

Weight loss	The patient scores 1 point if they experienced unintentional weight loss of > 4.5 kg or > 5% of body mass in the past 12 months (self-reported)
Muscle weakness	Using a dynamometer, 3 consecutive HGS measurements are taken. The patient scores 1 point if the average of the 3 values is below 20% of the expected value for sex and BMI, according to the values below:
	Men	Women
	IMC ≤ 24 Kg/m²2. Johansen KL, Chertow GM, Gilbertson DT, Herzog CA, Ishani A, Israni AK, et al. US Renal Data System 2021 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2022;79(4, Suppl 1):A8–12. doi: http://doi.org/10.1053/j.ajkd.2022.02.001. PubMed PMID: 35331382. https://doi.org/10.1053/j.ajkd.2022.02.0... : HGS≤29kg	IMC ≤ 23 Kg/m²2. Johansen KL, Chertow GM, Gilbertson DT, Herzog CA, Ishani A, Israni AK, et al. US Renal Data System 2021 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2022;79(4, Suppl 1):A8–12. doi: http://doi.org/10.1053/j.ajkd.2022.02.001. PubMed PMID: 35331382. https://doi.org/10.1053/j.ajkd.2022.02.0... : HGS≤17kg
	IMC 24.1–26 Kg/m²2. Johansen KL, Chertow GM, Gilbertson DT, Herzog CA, Ishani A, Israni AK, et al. US Renal Data System 2021 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2022;79(4, Suppl 1):A8–12. doi: http://doi.org/10.1053/j.ajkd.2022.02.001. PubMed PMID: 35331382. https://doi.org/10.1053/j.ajkd.2022.02.0... : HGS≤30kg	IMC 23.1–26 Kg/m²2. Johansen KL, Chertow GM, Gilbertson DT, Herzog CA, Ishani A, Israni AK, et al. US Renal Data System 2021 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2022;79(4, Suppl 1):A8–12. doi: http://doi.org/10.1053/j.ajkd.2022.02.001. PubMed PMID: 35331382. https://doi.org/10.1053/j.ajkd.2022.02.0... : HGS≤17.3kg
	IMC 26.1–28 Kg/m²2. Johansen KL, Chertow GM, Gilbertson DT, Herzog CA, Ishani A, Israni AK, et al. US Renal Data System 2021 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2022;79(4, Suppl 1):A8–12. doi: http://doi.org/10.1053/j.ajkd.2022.02.001. PubMed PMID: 35331382. https://doi.org/10.1053/j.ajkd.2022.02.0... : HGS≤30kg	IMC 26.1–29 Kg/m²2. Johansen KL, Chertow GM, Gilbertson DT, Herzog CA, Ishani A, Israni AK, et al. US Renal Data System 2021 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2022;79(4, Suppl 1):A8–12. doi: http://doi.org/10.1053/j.ajkd.2022.02.001. PubMed PMID: 35331382. https://doi.org/10.1053/j.ajkd.2022.02.0... : HGS≤8kg
	IMC ≥ 28 Kg/m²2. Johansen KL, Chertow GM, Gilbertson DT, Herzog CA, Ishani A, Israni AK, et al. US Renal Data System 2021 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2022;79(4, Suppl 1):A8–12. doi: http://doi.org/10.1053/j.ajkd.2022.02.001. PubMed PMID: 35331382. https://doi.org/10.1053/j.ajkd.2022.02.0... : HGS≤32kg	IMC ≥ 29 Kg/m²2. Johansen KL, Chertow GM, Gilbertson DT, Herzog CA, Ishani A, Israni AK, et al. US Renal Data System 2021 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2022;79(4, Suppl 1):A8–12. doi: http://doi.org/10.1053/j.ajkd.2022.02.001. PubMed PMID: 35331382. https://doi.org/10.1053/j.ajkd.2022.02.0... : HGS≤21kg
Exhaustion	The patient is asked questions 7 and 20 from the Center for Epidemiological Studies Depression (CES-D) questionnaire:
	“How often in the past week did you feel that everything you did demanded a lot of effort?”
	“How often in the past week did you feel you could not get going?”
	The alternatives are as follows:
	(0) Rarely or none of the time/1 day
	(1) Some or a little of the time/1–2 days
	(2) Occasionally or a moderate amount of the time/3–4 days
	(3) Most or all of the time/always
	The patient scores 1 point if they answer 2 or 3 to either of the two questions.
Slowness	The walk test is performed, and the average of 3 consecutive measurements of the time taken to cover a distance of 4.6 meters is obtained. The patient scores (1 point) if their performance does not meet the minimum expected for their sex and height, as outlined below:
	Men	Women
	Height ≤ 173cm: Time ≥ 7 sec	Height ≤ 159cm: Time ≥ 7 sec
	Height ≥ 173cm: Time ≥ 6 sec	Height ≥ 159cm: Time ≥ 7 sec
Low physical activity	The patient scores 1 point if their weekly energy expenditure was lower than 383 kcal for men and 270 kcal for women in the past two weeks, based on the short version of the Minnesota Leisure Time Activity44
Once the points have been added up, the result is as follows^* Note: *The original classification by Fried et al.24 considers a score of 1 as pre-frail. However, in 2013, McAdams-DeMarco et al. proposed an adaptation for the CKD population, considering a score of 1 as non-frail45. :
	0–1 point = non-frail
	2 points: pre-frail
	3–5 points = frail