ReviewFrailty and chronic kidney disease: A systematic review
Introduction
Frailty describes a state of increased vulnerability to health problems. There are two acknowledged conceptualisations of the term, which have resulted in different approaches to its measurement (McMillan & Hubbard, 2012). Firstly, frailty can be thought of as a syndrome with sarcopenia as the key pathophysiological feature (Fried, Tangen, & Walston, 2001): this facilitates the measurement of frailty using a specific set of signs and symptoms. This approach, developed by Linda Fried, defines five criteria that establish a phenotype for frailty: slowness, weakness, low physical activity, exhaustion and shrinkage (Fried et al., 2001).
The second approach, known as the frailty index approach, views frailty as a state of deficit accumulation that begins at the cellular level and leads to a loss of redundancy in organ systems (Jeffery, Shum, & Hubbard, 2013; Rockwood & Mitnitski, 2007; Ensrud, Ewing, & Taylor, 2007); here, frailty is quantified by counting deficits across multiple systems.
Patients who are frail, regardless of how it is measured, experience a decline in physical function and are at an increased risk of adverse health outcomes. Although there is a strong positive correlation between frailty and chronological age, patients with chronic disease also appear to be predisposed to frailty (Weiss, 2011).
The relationship between chronic kidney disease (CKD) and frailty is not completely understood. Studies have shown that inflammation is associated with frailty in many chronic diseases and this suggests a ‘shared pathophysiology’ of frailty (Jeffery et al., 2013). In particular, the pro-inflammatory cytokines interleukin-6 and tumour necrosis factor alpha may have a role in age-related muscle atrophy and sarcopenia, which are key features of frailty (Hubbard & Woodhouse, 2010). Shlipak et al. (Shlipak, Fried, & Crump, 2003) demonstrated that there are raised levels of pro-inflammatory cytokines in CKD patients. However, further research is needed to investigate the causal relationship between inflammation and frailty specifically in patients with CKD.
A previous systematic review (studies published to 2012) explored frailty in pre-dialysis patients and showed an association between frailty and CKD (Walker, Gill, & Macdonald, 2013). Here, we update and expand this evidence, by including patients on dialysis as well as in kidney transplant recipients. The aims of the systematic review were to explore how frailty is measured in patients with CKD, evaluate the relationship between frailty and severity of kidney failure and assess whether it predicts outcomes such as mortality and hospitalization.
Section snippets
Search strategy
The following search terms were used to identify articles that assessed frailty in patients with CKD: ‘Chronic kidney disease’ OR ‘kidney disease’ OR ‘Renal Insufficiency’ OR ‘dialysis’ OR ‘kidney failure’ OR ‘renal failure’ AND ‘frailty’.
The focus of this review was on assessment of frailty status. Thus, we did not broaden the search criteria for frailty to include geriatric or functional assessments. The literature search was conducted using online databases including Pubmed, Medline, Web of
Data analysis
Two independent reviewers examined the abstracts for relevance to the study criteria. Where there was a difference of opinion about inclusion of the study, a third reviewer was consulted.
A data extraction table was created which included information about the demographics of the study population, the sample size, method of frailty assessment, CKD measurement and outcome variables such as mortality rates and hospitalization.
Each article in the systematic review was assessed for quality using the
Results
The literature search yielded 540 articles. Forty-eight articles met the inclusion criteria and were selected for full text review. After the full text review a further 16 studies were excluded from further analysis for the following reasons: article did not measure frailty in the study population (n = 3); not available in English (n = 2); did not measure frailty in a CKD population (n = 3); repeated analyses on the same study population (n = 8); and one article whose results were not available for the
Frailty and the kidney transplant recipient
Three studies have investigated frailty in kidney transplant recipients. McAdams De-Marco et al. (McAdams-DeMarco, Law, & Salter, 2013b) demonstrated that incident frailty increased the risk of hospital readmission amongst kidney transplant recipients (Relative Risk = 1.61, 95% CI 1.18–2.19). This risk persisted after adjustment for age, gender, co-morbidity, time spent on dialysis and donor factors. Another study by Garonzik-Wang et al. (Garonzik-Wang, Govindan, & Grinnan, 2012) showed that
Discussion
In this systematic review of frailty in patients with CKD, the prevalence of frailty increased with poorer kidney function and was highest in patients receiving dialysis. Frailty was a significant predictor of adverse health outcomes, particularly in those with severe CKD stages. However, we found differences in frailty assessment and estimation of GFR and this may have influenced the reported prevalence of frailty.
The Fried phenotype provided the basis for frailty assessment in the majority of
Conclusion
Based on the number of studies, consistency and quality of the findings, there is strong evidence that frailty is associated with CKD and that patients with more severe CKD are more likely to be frail. Frailty predicts poor outcomes in patients with CKD including an increased risk of mortality and hospitalization. There is a need to better understand causality and why frailty is associated with adverse health outcomes in patients with CKD. Further research should also explore different methods
Conflicts of interest
None.
References (48)
- et al.
Frailty in elderly people
Lancet
(2013) - et al.
Association of frailty with body composition among patients on hemodialysis
Journal of Renal Nutrition
(2013) - et al.
Emerging drug therapies for frailty
Maturitas
(2013) - et al.
Influence of frailty on health-related quality of life in pre-dialysis patients with chronic kidney disease in Korea: A cross-sectional study
Health and Quality of Life Outcomes
(2015) - et al.
Frailty and early hospital readmission after kidney transplantation
American Journal of Transplantation
(2013) - et al.
A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged African Americans
The Journal of Nutrition Health and Aging
(2012) - et al.
A prospective study of frailty in nephrology-referred patients with CKD
AJKD
(2012) - et al.
The presence of frailty in elderly persons with chronic renal insufficiency
AJKD
(2004) Frailty and chronic diseases in older adults
Clinics in Geriatric Medicine
(2011)- et al.
Chronic kidney disease (CKD) is an independent risk factor for long-term care insurance (LTCI) need certification among older Japanese adults: A two-year prospective cohort study
Archives of Gerontology and Geriatrics
(2013)
Frailty and mortality in dialysis: Evaluation of a clinical frailty scale
CJASN
Frailty, dialysis initiation, and mortality in end-stage renal disease
Archives of Internal Medicine
Simple self-report FRAIL scale might be more closely associated with dialysis complications than other frailty screening instruments in rural chronic dialysis patients
Nephrology
Kidney function and prevalent and incident frailty
CJASN
Association of Frailty based on self-reported physical function with directly measured kidney function and mortality
BMC Nephrology
Association of self-reported frailty with falls and fractures among patients new to dialysis
BMJ Supportive & Palliative Care
High prevalence of frailty in end-stage renal disease
International Urology and Nephrology
Frailty and risk of falls, fracture, and mortality in older women: The study of osteoporotic fractures
Journals of Gerontology Series A: Biological Sciences and Medical Science
Frailty in older adults: Evidence for a phenotype
Journals of Gerontology Series A: Biological Sciences and Medical Sience
Frailty and delayed graft function in kidney transplant recipients
Archives of Surgery
An epidemiological appraisal instrument—A tool for evaluation of epidemiological studies
Ergonomics
Cystatin C and frailty in older men
Journal of the American Geriatrics Society
Frailty, inflammation and the elderly
Biogerontology
Feasibility and construct validity of a Frailty index for patients with chronic kidney disease
Australasian Journal on Ageing
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