Frailty in chronic kidney disease

Abstract

Frailty is regarded as the most problematic consequence of aging. Whilst there is no precise definition for frailty, most clinicians agree that patients who are frail are vulnerable to poor health. Frailty can be conceptualised as a syndrome with a set of symptoms and signs as described by Fried and colleagues. Alternatively, frailty can be considered as a state, where deficits in health accumulate over time n this is the frailty index (FI) approach.Patients with chronic kidney disease (CKD) are at risk of frailty. CKD has effects in multiple systems and it leads to accelerated manifestation of frailty, especially in those who are on dialysis. The Fried approach to frailty assessment has been applied in numerous settings of patients with CKD. However, there are limitations of the Fried approach especially when the prevalence of frailty is high, and a more precise measure is needed of the severity of frailty in an individual.The thesis begins with a systematic review of frailty in patients with CKD. It focuses on how frailty is assessed, including the Fried approach and other assessment methods; differences in frailty between dialysis and pre-dialysis patients; and how frailty changes across the spectrum of severity in kidney function. The systematic review yielded 37 articles encompassing 53,000 patients with CKD. The most common method of frailty assessment was the Fried approach (n=27 articles, 73%). The prevalence of frailty ranged between 7% in a population of pre-dialysis patients with CKD to 73% in patients on dialysis. There was considerable heterogeneity in how the studies defined the Fried phenotype and this impacted on the reported prevalence of frailty. Regardless of the method of assessment, frailty was associated with an increased risk of mortality and hospitalization.The systematic review highlighted gaps in the current evidence, especially in better delineating risk amongst patients on dialysis where the prevalence of frailty may be high. This leads to the next chapter of the thesis, a prospective study of the Frailty Index in CKD (FI-CKD). The aim of the study was to investigate the frailty index (FI) in outpatients with pre-dialysis and dialysis dependent CKD. Associations between FI and kidney function were explored as well as the relationship between FI and change in kidney function, mortality and hospitalization after twelve months of follow up. Amongst 314 patients, the mean FI was 0.29 (SD 0.13) corresponding to a clinical description of mild to moderate frailty. FI was associated with an increased risk of mortality (OR: 1.8; 95% CI 1.77 n 2.44) and hospitalization (OR 1.3 95% CI 1.06-1.5). Patients with a higher CKD stage were significantly more likely to have a higher FI. However, there was no significant differences in the average FI between dialysis and pre-dialysis patients, perhaps due to the limited number of patients on dialysis (n=86, 27%) or due to selection bias.nThe final chapter reviews the implications of the prospective study for clinical practice. FI may be incorporated into electronic medical records to provide more contemporaneous support for clinical decision making. The studies described in this thesis have provided the basis for a longitudinal investigation of frailty in patients with end stage kidney disease and exploring changes in FI with dialysis initiation versus conservative management.nn