Glomerular Filtration Rate Equations Overestimate Creatinine Clearance in Older Individuals Enrolled in the Baltimore Longitudinal Study on Aging: Impact on Renal Drug Dosing

OBJECTIVES To evaluate the performance of kidney function estimation equations and to determine the frequency of drug dose discordance in an older population. DESIGN Cross-sectional analysis of data from community-dwelling volunteers randomly selected from the Baltimore Longitudinal Study of Aging from January 1, 2005, to December 31, 2010. SUBJECTS A total of 269 men and women with a mean +/- SD age of 81 +/- 6 years, mean serum creatinine concentration (S-cr) of 1.1 +/- 0.4 mg/dl, and mean 24-hour measured creatinine clearance (mCl(cr)) of 53 +/- 13 ml/minute. MEASUREMENTS AND MAIN RESULTS Kidney function was estimated by using the following equations: Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The performance of each equation was assessed by measuring bias and precision relative to mCl(cr). Dose calculation errors (discordance) were determined for 10 drugs requiring renal dosage adjustments to avoid toxicity when compared with the dosages approved by the Food and Drug Administration. The CG equation was the least biased estimate of mCl(cr). The MDRD and CKD-EPI equations were significantly positively biased compared with CG (mean +/- SD 34 +/- 20% and 22 +/- 15%, respectively, p<0.001) and mCl(cr) (29 +/- 47% and 18 +/- 40%, respectively, p<0.001). Rounding low S-cr values (less than 1.0 mg/dl) up to an arbitrary value of 1.0 mg/dl resulted in CG values (44 +/- 10 ml/minute) that were significantly lower than mCl(cr) (56 +/- 12 ml/minute, p<0.001) and CG (56 +/- 15 ml/minute, p<0.001). The MDRD and CKD-EPI equations had median dose discordance rates of 28.6% and 22.9%, respectively. CONCLUSION The MDRD and CKD-EPI equations significantly overestimated creatinine clearance (mCl(cr) and CG) in elderly individuals. This leads to dose calculation errors for many drugs, particularly in individuals with severe renal impairment. Thus equations estimating glomerular filtration rate should not be substituted in place of the CG equation in older adults for the purpose of renal dosage adjustments. In addition, the common practice of rounding or replacing low S-cr values with an arbitrary value of 1.0 mg/dl for use in the CG equation should be avoided. Additional studies that evaluate alternative eGFR equations in the older populations that incorporate pharmacokinetic and pharmacodynamic outcomes measures are needed.