Increased mortality after kidney transplantation in mildly frail recipients

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ABSTRACT

Background

Physical Frailty Phenotype (PFP) is the most used frailty instrument among kidney transplant recipients, classifying patients as pre-frail if they have 1–2 criteria and as frail if they have ≥3. However, different definitions of robustness have been used among renal patients, including only those who have 0 criteria, or those with 0–1 criteria. Our aim was to determine the impact of one PFP criterion on transplant outcomes.

Methods

We undertook a retrospective study of 296 kidney transplant recipients who had been evaluated for frailty by PFP at the time of evaluating for transplantation.

Results

Only 30.4% of patients had 0 criteria, and an additional 42.9% showed one PFP criterion. As PFP score increased, a higher percentage of women and cerebrovascular disease were found. Recipients with 0–1 criteria had lower 1-year mortality after transplant than those with ≥2 (1.8% vs 10.1%), but this difference was already present when we only considered those who scored 0 (mortality 1.1%) and 1 (mortality 2.4%) separately. The multivariable analysis confirmed that one PFP criterion was associated to a higher risk of patient death after kidney transplantation [hazard ratio 3.52 (95% confidence interval 1.03–15.9)].

Conclusions

Listed kidney transplant candidates frequently show only one PFP frailty criterion. This has an independent impact on patient survival after transplantation.

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Most cited references 21

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Frailty in older adults: evidence for a phenotype.

L P Fried, C Tangen, J Walston … (2001)

Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established. To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality. Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline). This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.

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Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participants

Peter Hanlon, Barbara Nicholl, Bhautesh Jani … (2018)

Summary Background Frailty is associated with older age and multimorbidity (two or more long-term conditions); however, little is known about its prevalence or effects on mortality in younger populations. This paper aims to examine the association between frailty, multimorbidity, specific long-term conditions, and mortality in a middle-aged and older aged population. Methods Data were sourced from the UK Biobank. Frailty phenotype was based on five criteria (weight loss, exhaustion, grip strength, low physical activity, slow walking pace). Participants were deemed frail if they met at least three criteria, pre-frail if they fulfilled one or two criteria, and not frail if no criteria were met. Sociodemographic characteristics and long-term conditions were examined. The outcome was all-cause mortality, which was measured at a median of 7 years follow-up. Multinomial logistic regression compared sociodemographic characteristics and long-term conditions of frail or pre-frail participants with non-frail participants. Cox proportional hazards models examined associations between frailty or pre-frailty and mortality. Results were stratified by age group (37–45, 45–55, 55–65, 65–73 years) and sex, and were adjusted for multimorbidity count, socioeconomic status, body-mass index, smoking status, and alcohol use. Findings 493 737 participants aged 37–73 years were included in the study, of whom 16 538 (3%) were considered frail, 185 360 (38%) pre-frail, and 291 839 (59%) not frail. Frailty was significantly associated with multimorbidity (prevalence 18% [4435/25 338] in those with four or more long-term conditions; odds ratio [OR] 27·1, 95% CI 25·3–29·1) socioeconomic deprivation, smoking, obesity, and infrequent alcohol consumption. The top five long-term conditions associated with frailty were multiple sclerosis (OR 15·3; 99·75% CI 12·8–18·2); chronic fatigue syndrome (12·9; 11·1–15·0); chronic obstructive pulmonary disease (5·6; 5·2–6·1); connective tissue disease (5·4; 5·0–5·8); and diabetes (5·0; 4·7–5·2). Pre-frailty and frailty were significantly associated with mortality for all age strata in men and women (except in women aged 37–45 years) after adjustment for confounders. Interpretation Efforts to identify, manage, and prevent frailty should include middle-aged individuals with multimorbidity, in whom frailty is significantly associated with mortality, even after adjustment for number of long-term conditions, sociodemographics, and lifestyle. Research, clinical guidelines, and health-care services must shift focus from single conditions to the requirements of increasingly complex patient populations. Funding CSO Catalyst Grant and National Health Service Research for Scotland Career Research Fellowship.

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Frailty as a novel predictor of mortality and hospitalization in individuals of all ages undergoing hemodialysis.

Dorry L Segev, Luis F Gimenez, B J Boyarsky … (2013)

To quantify the prevalence of frailty in adults of all ages undergoing chronic hemodialysis, its relationship to comorbidity and disability, and its association with adverse outcomes of mortality and hospitalization. Prospective cohort study. Single hemodialysis center in Baltimore, Maryland. One hundred forty-six individuals undergoing hemodialysis enrolled between January 2009 and March 2010 and followed through August 2012. Frailty, comorbidity, and disability on enrollment in the study and subsequent mortality and hospitalizations. At enrollment, 50.0% of older (≥ 65) and 35.4% of younger (<65) individuals undergoing hemodialysis were frail; 35.9% and 29.3%, respectively, were intermediately frail. Three-year mortality was 16.2% for nonfrail, 34.4% for intermediately frail, and 40.2% for frail participants. Intermediate frailty and frailty were associated with a 2.7 times (95% confidence interval (CI) = 1.02-7.07, P = .046) and 2.6 times (95% CI = 1.04-6.49, P = .04) greater risk of death independent of age, sex, comorbidity, and disability. In the year after enrollment, median number of hospitalizations was 1 (interquartile range 0-3). The proportion with two or more hospitalizations was 28.2% for nonfrail, 25.5% for intermediately frail, and 42.6% for frail participants. Although intermediate frailty was not associated with number of hospitalizations (relative risk = 0.76, 95% CI = 0.49-1.16, P = .21), frailty was associated with 1.4 times (95% CI = 1.00-2.03, P = .049) more hospitalizations independent of age, sex, comorbidity, and disability. The association between frailty and mortality (interaction P = .64) and hospitalizations (P = .14) did not differ between older and younger participants. Adults of all ages undergoing hemodialysis have a high prevalence of frailty, more than five times as high as community-dwelling older adults. In this population, regardless of age, frailty is a strong, independent predictor of mortality and number of hospitalizations. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

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Author and article information

Contributors

María José Pérez-Sáez:

ORCID: https://orcid.org/0000-0002-8601-2699

Carlos E Arias-Cabrales

Dolores Redondo-Pachón

Carla Burballa

Anna Buxeda

Anna Bach

Anna Faura

Ernestina Junyent

Ester Marco

Leocadio Rodríguez-Mañas:

ORCID: https://orcid.org/0000-0002-6551-1333

Marta Crespo

Julio Pascual

Journal

Journal ID (nlm-ta): Clin Kidney J

Journal ID (iso-abbrev): Clin Kidney J

Journal ID (publisher-id): ckj

Title: Clinical Kidney Journal

Publisher: Oxford University Press

ISSN (Print): 2048-8505

ISSN (Electronic): 2048-8513

Publication date Collection: November 2022

Publication date (Electronic): 23 June 2022

Publication date PMC-release: 23 June 2022

Volume: 15

Issue: 11

Pages: 2089-2096

Affiliations

Nephrology Department , Hospital del Mar, Barcelona, Spain

Physical Medicine & Rehabilitation Department , Parc de Salut Mar (Hospital del Mar-Hospital de l'Esperança), Rehabilitation Research Group, Hospital del Mar Research Institute, Universitat Autònoma de Barcelona , Barcelona, Spain

Geriatrics Department, Hospital Universitario de Getafe , Madrid, Spain

Nephrology Department , Hospital del Mar, Barcelona, Spain

Nephrology Department , Hospital Universitario 12 de Octubre, Madrid, Spain

Author notes

Correspondence to: Julio Pascual; E-mail: julpascual@ 123456gmail.com

These authors contributed equally to this work.

Author information

María José Pérez-Sáez https://orcid.org/0000-0002-8601-2699

Leocadio Rodríguez-Mañas https://orcid.org/0000-0002-6551-1333

Article

Publisher ID: sfac159

DOI: 10.1093/ckj/sfac159

PMC ID: 9613422

PubMed ID: 36325004

SO-VID: aa1a0545-1152-4992-a32e-0e4265e6a5d7

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

History

Date received : 31 March 2022

Date: 26 July 2022

Page count

Pages: 8

Funding

Funded by: FIS-FEDER;

Award ID: PI19/00037

Funded by: Instituto de Salud Carlos III, DOI 10.13039/501100004587;

Funded by: Spanish Society of Transplant;

Funded by: Rio Hortega;

Award ID: CM19/00004

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Increased mortality after kidney transplantation in mildly frail recipients

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ABSTRACT

Background

Methods

Results

Conclusions

Graphical Abstract

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Karger: Nephrology

Most cited references 21

Frailty in older adults: evidence for a phenotype.

Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participants

Frailty as a novel predictor of mortality and hospitalization in individuals of all ages undergoing hemodialysis.

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Cited by 4

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