Frailty and chronic kidney disease: A systematic review

Highlights

• Frailty is prevalent in CKD patients with those on dialysis being the most frail.

• Frailty is associated with an increased risk of mortality and hospitalization.

• Most common method of frailty assessment in the CKD cohort is the Fried phenotype.

• Reported frailty prevalence changes depending on the method of frailty assessment.

Abstract

Objective

Frailty is associated with increased vulnerability to poor health. There is growing interest in understanding the association between frailty and chronic kidney disease (CKD). This systematic review explored how frailty is measured in patients with CKD and the association between frailty and adverse outcomes across different stages of renal impairment.

Study design

Systematic analysis of peer reviewed articles.

Data sources

Pubmed, Medline, Web of Science and Cochrane were used to identify the articles.

Data synthesis

Articles published before the 17th of September 2016, that measured frailty in patients with CKD was eligible for the systematic review. Two independent researchers assessed the eligibility of the articles. Quality of the articles was assessed using the Epidemiological Appraisal Instrument.

Results

The literature search yielded 540 articles, of which 32 met the study criteria and were included in the review (n = 36,076, age range: 50–83 years). Twenty-three (72%) studies used or adapted the Fried phenotype to measure frailty. The prevalence of frailty ranged from 7% in community-dwellers (CKD Stages 1–4) to 73% in a cohort of patients on haemodialysis. The incidence of frailty increased with reduced glomerular filtration rate. Frailty was associated with an increased risk of mortality and hospitalization.

Conclusion

Frailty is prevalent in patients with CKD and it is associated with an increased risk of adverse health outcomes. There are differences in the methods used to assess frailty and this hinders comparisons between studies.

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.