Comparison of the Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease, and Cockcroft-Gault Equations for Drug Dosing in the Elderly Population

Purpose: The Cockcroft-Gault (CG) equation provides an estimate of creatinine clearance (CrCl) and has been the standard for dosing medications based on kidney function.  The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations provide an estimate of glomerular filtration rate (eGFR), are more accurate for staging CKD, and have recently been advocated for drug dosing.  The primary objective of this study was to determine whether a dosing discordance exists for a selected group of renally eliminated medications in an elderly population when using CKD-EPI or MDRD to estimate kidney function versus CG. 

Methods: Patients ≥ 65 years of age were included in this retrospective, observational analysis.  A theoretical dosing simulation was conducted by calculating eGFR and eCrCl to determine whether a dose adjustment was recommended per the manufacturers’ labeling for the following renally eliminated medications: allopurinol, enoxaparin, gabapentin, piperacillin/tazobactam, sulfamethoxazole/trimethoprim.  Data was analyzed for discordance among the three estimating equations for drug dosing. 

Results: A total of 4160 patients were included: 98% male, 79% Caucasian, mean age 74 ± 7.4 years, mean eCrCl 61 ± 19 mL/min, mean eGFR/BSA (MDRD) 75 ± 21 mL/min, mean eGFR/BSA (CKD-EPI) 75 ± 23 mL/min.  The observed dosing discordance was: allopurinol 0.5%, enoxaparin 2.9%, gabapentin 27.1%, piperacillin/tazobactam 9.1%, and sulfamethoxazole/trimethoprim 3.1%.

Conclusion: CG led to medication adjustments more often than CKD-EPI and MDRD.  Use of eGFR as opposed to eCrCl for medication dosing resulted in higher doses being prescribed more often in the elderly population.