Comparison of the modification of diet in renal disease and Cockcroft-Gault equations for antimicrobial dosage adjustments.

Background: Direct measurement of glomerular filtration rate (GFR) is considered to be the most accurate method of assessing kidney function, albeit difficult and costly. With the derivation of the Modification of Diet in Renal Disease (MDRD) equation to estimate GFR in patients with chronic kidney disease, questions exist as to whether this method should be preferred over the Cockcroft-Gault (CG) equation when making dosage adjustments for renally eliminated antimicrobials.

Objective: To determine whether a difference exists when making antimicrobial dosage adjustments in patients with chronic kidney disease based on estimation of GFR using the MDRD and CG equations.

Methods: We conducted an observational analysis of 409 patients with chronic kidney disease who were admitted to a tertiary care facility with an inpatient dialysis center and nephrology unit. GFR was calculated using both the 4- or 6-variable MDRD equation and the CG equation and compared using correlation and Bland-Altman methodology. Dosage discordance rates of the selected antimicrobials were determined on the basis of manufacturer renal dose recommendations.

Results: Average +/- SD GFR for all patients using the CG equation was 34.8 +/- 12 mL/min and, using the MDRD equation, was 40.2 +/- 12 mL/min (absolute mean difference 5.40; 95% CI 4.66 to 6.15; p < 0.001). The correlation coefficient between the 2 estimations, among all patients, was excellent (r = 0.80). The Bland-Altman plot yielded limits of agreement of -9.8 and 20.6; thus, the MDRD estimation may range from 9.8 mL/min below to 20.6 mL/min above the CG estimation for 95% of the cases. A discordance rate of 21-37% (p < 0.001) existed among the recommended dosing adjustments of the selected antimicrobials.

Conclusions: This analysis demonstrated statistically significant differences between the CG and MDRD equations, resulting in different dosing recommendations in 21-37% of patients. The clinical significance of these differences is uncertain in the absence of data regarding clinical outcomes that would result from the use of the discordant doses.