Frailty Associated With Risk of ESKD, Mortality in Patients With CKD

A retrospective cohort study found that frailty was prevalent in patients with chronic kidney disease (CKD) and that the adverse effects could include end stage kidney disease (ESKD) and mortality.

An association has been found between the adverse effects of chronic kidney disease (CKD) and frailty, which is prevalent in patients with CKD, according to new study findings published in Journal of Cachexia, Sarcopenia and Muscle.

Early detection of frailty has made it easier to treat and improve patients who show early symptoms, especially because many cases of frailty arereversible, note the study authors. This study aimed to identify the prevalence of frailty in patients with CKD, to investigate changes in frailty status, and to explore the association between frailty and rates of incident dialysis, kidney transplantation, and all-cause and cardiovascular mortality.

The study used the Clinical Practice Research Datalink (CPRD) for the its population, which is an ongoing UK primary care database of anonymized medical records that covers approximately 19 million people from more than 700 health care practices. One million patients initially were randomly selected who were registered in the CPRD between January 1, 2006, and December 31, 2015. Patients were included if they were registered in the practice for 12 or more months and had 2 or more consecutive creatinine level.

Frailty was determined using an electronic frailty index. Patients were included in the CKD cohort by the date when their second estimated glomerular filtration rate (eGFR) was less than 60 mL/min/1.73m2.

There were 819,893 patients included, and 140,674 had CKD at baseline. The mean (SD) age was 77.5 (9.7) years, 38.0% were male, and 97.4% were White. The mean eGFR was 46.1 (9.9) mL/min/1.73m2, with most participants having stage 3a disease (61.3%).

Participants with CKD were mostly frail, with 75.3% having mild frailty or worse vs 45.4% in participants without CKD. Prevalence of moderate and severe frailty was highest in advanced CKD stages, with 87.2% of patients with stage 4 CKD reporting frailty. The median (IQR) number of deficits in the CKD group was 7 (5-9) vs 4 (3-6) in the patients without CKD.

In a cohort of 405,719 participants who were not considered frail, of which 34,791 (8.6%) had CKD, the risk of developing frailty also was assessed. There were 24,187 (69.5%) participants with CKD who developed frailty in a median follow-up time of 3.0 (1.3-5.4) years; 54.1% developed mild, 13.6% developed moderate, and 1.7% developed severe frailty. Only 43.2% of those without CKD developed frailty in the same time period.

Those with CKD had a 2% increased risk of mild frailty (HR, 1.02; 95% CI, 1.01-1.04), a 30% increased risk of moderate frailty (HR, 1.30; 95% CI, 1.26-1.34), and a 50% increased risk of severe frailty (HR, 1.50; 95% CI, 1.37-1.65). The researchers also found that mild frailty increased the risks of all-cause mortality by 22% (HR, 1.22; 95% CI, 1.19-1.24), moderate frailty by 60% (HR, 1.60; 95% CI, 1.56-1.63), and severe frailty by 116% (HR, 2.16; 95% CI, 2.11-2.22) in patients with CKD compared with being nonfrail. Cardiovascular mortality had a 2- to 3-fold increased risk in those who were frail vs nonfrail patients.

Frailty increased the risks of requiring dialysis in all patients but especially in patients with CKD vs those who were not considered frail (mild: HR, 1.50; 95% CI, 1.16-1.94; moderate: HR, 1.63; 95% CI, 1.24-2.31; severe: HR, 2.02; 95% CI, 1.28-3.19).

There were some limitations to this study. The researchers were not able to account for the worsening of comorbidities over time, and they removed CKD as a deficit in the calculations, which may have resulted in an underestimation of frailty.

The authors concluded that frailty is highly prevalent and predictive of adverse outcomes in patients with CKD, specifically all-cause and cardiovascular mortality, and dialysis.

“Our study highlights the importance of routinely assessing frailty, particularly moderate and severe, among patients with CKD, with a view to considering targeted interventions that aim to improve prognosis,” the authors wrote.


Wilkinson TJ, Miksza J, Zaccardi F, et al. Associations between frailty trajectories and cardiovascular, renal, and mortality outcomes in chronic kidney disease. J Cachexia Sarcopenia Muscle. Published online July 19, 2022. doi:10.1002/jcsm.13047

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