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

Shoshana H. Ballew, Yan Chen, Natalie R. Daya, Job G. Godino, B. Gwen Windham, Mara McAdams-DeMarco, Josef Coresh, Elizabeth Selvin, Morgan E. Grams

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


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 < 60 mL/min/1.73 m2, 2,480 (50%) had eGFRcys < 60 mL/min/1.73 m2, and 1,006 (20%) had albuminuria with albumin excretion ≥ 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 albumin-creatinine ratio. Frail individuals with eGFRcr of 60 to <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 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.

Original languageEnglish (US)
Pages (from-to)228-236
Number of pages9
JournalAmerican Journal of Kidney Diseases
Issue number2
StatePublished - Feb 1 2017


  • Frailty
  • albuminuria
  • biomarker
  • chronic kidney disease (CKD)
  • estimated glomerular filtration rate (eGFR)
  • frail
  • geriatric
  • older adults
  • polypharmacy
  • prefrail
  • reduced kidney function
  • serum creatinine
  • serum cystatin C
  • urine albumin

ASJC Scopus subject areas

  • Nephrology


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