Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Background Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Study Design Observational study. Setting & Participants 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011–2013). Predictor Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr) and serum cystatin C (eGFRcys) and urine albumin-creatinine ratio (ACR). Outcomes Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). Results In total, 341 participants (7%) were classified as frail, 1475 (30%) had eGFRcr <60 ml/min/1.73 m2, 2480 (50%) had eGFRcys <60 ml/min/1.73 m2, and 1006 (20%) had albuminuria ≥30 mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys <60 ml/min/1.73 m2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and ACR. Frail individuals with eGFRcr 60–<75 ml/min/1.73 m2 were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45–<60, 32% to 30–<45, and 3% to <30 ml/min/1.73 m2). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of non-frail), including classes requiring kidney clearance (e.g., digoxin) and associated with falls and subsequent complications (e.g., hypnotic/sedatives, anticoagulants). Limitations Cross-sectional study design. Conclusions Frail individuals had a high prevalence of reduce kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr. Given the substantial medication burden and uncertainty in CKD classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population.

Diagnostic Accuracy of Frailty Screening Methods in Advanced Chronic Kidney Disease

“…Comparable to other reports, the prevalence of frailty increased with worsening kidney function in this cohort [5,38,39]. There was a similar age between non-frail and frail groups, highlighting that frailty is a syndrome that is not merely due to the ageing process.…”

Risk-stratified surveillance and cost effectiveness of follow-up after radical cystectomy in patients with muscle-invasive bladder cancer.

“…The other potential factor that influencing on poor prognosis was frailty. Patients with CKD and CVD are more likely to be frail [22] because these are likely to exist in combination with comorbid conditions, disability, and polypharmacy [23,24]. In addition, frailty is also one of the important parameters of cancers [25,26].…”

Frailty in chronic kidney disease

“…A study by Roshanravan et al found that the relationship between frailty and CKD was attenuated when using creatinine instead of Cystatin C to estimate GFR (28). This was supported by a more recent retrospective analysis by Ballew et al of 4987 community dwellers comparing cystatin C and creatinine clearance and the relationship with frailty (42). In five studies, there was significant increase in the risk of frailty with eGFR less than 45mLs per minute (16,(27)(28)(29)(30).…”

“…23,25,26,29- 33 Frailty also predicted an increased risk of falls in patients with CKD. 34,42 In the kidney transplant recipient, frailty was associated with an increased risk of early hospital readmission and delayed graft function. 35,36 Patients who were frail prior to transplantation were also more likely to have improvement in frailty after transplantation.…”

“…In the remaining study, only patients with an eGFR less than 30mLs per minute were at a statistically significant increased risk of frailty because those with an eGFR >45 was used as the reference population (40). The study by Ballew et al demonstrated a significant relationship between odds of frailty with kidney function estimated with cystatin C, with the more severe the kidney disease the greater the odds of frailty (42).…”