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 (eGFR _cr) and serum cystatin C (eGFR _cys) 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 eGFR _cr <60 ml/min/1.73 m ², 2480 (50%) had eGFR _cys <60 ml/min/1.73 m ², and 1006 (20%) had albuminuria ≥30 mg/g. Among frail participants, prevalences of eGFR _cr and eGFR _cys <60 ml/min/1.73 m ² were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFR _cr and a strong association with eGFR _cys and ACR. Frail individuals with eGFR _cr 60–<75 ml/min/1.73 m ² were frequently reclassified to lower eGFR categories using eGFR _cys (49% to 45–<60, 32% to 30–<45, and 3% to <30 ml/min/1.73 m ²). 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 eGFR _cys versus eGFR _cr. 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.