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

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).

PREDICTORS: Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr ) and serum cystatin C level (eGFRcys ) and urine albumin-creatinine ratio.

OUTCOME: Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity).

RESULTS: 341 (7%) participants were classified as frail, 1,475 (30%) had eGFRcr <60mL/min/1.73m2 , 2,480 (50%) had eGFRcys <60mL/min/1.73m2 , and 1,006 (20%) had albuminuria with albumin excretion ≥ 30mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys <60mL/min/1.73m2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and albumin-creatinine ratio. Frail individuals with eGFRcr of 60 to <75mL/min/1.73m2 were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45-<60, 32% to 30-<45, and 3% to <30mL/min/1.73m2 ). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants).

LIMITATIONS: Cross-sectional study design.

CONCLUSIONS: Frail individuals had a high prevalence of reduced kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr . Given the substantial medication burden and uncertainty in chronic kidney disease classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population.