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

Abstract

Objectives To evaluate 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–December 31, 2010. Subjects Two hundred sixty-nine men and women with a mean ± SD age of 81 ± 6 years, mean serum creatinine concentration (Scr) of 1.1 ± 0.4 mg/dl, and mean measured 24-hour creatinine clearance (mClcr) 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 Study (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The performance of each equation was assessed by measuring bias and precision relative to mClcr. Dose calculation errors (discordance) were determined for 10 drugs requiring renal dosage adjustments to avoid toxicity when compared to the FDA-approved dosages. The CG equation was the least biased estimate of mClcr. The MDRD and CKD-EPI equations were significantly positively biased compared to CG (mean ± SD 34 ± 20% and 22 ± 15%, respectively, p<0.001) and mClcr (29 ± 47% and 18 ± 40%, respectively, p<0.001). Rounding low Scr values (< 1.0 mg/dl) up to an arbitrary value of 1.0 mg/dL resulted in CG values (44±10 mL/min) that were significantly lower than mClcr (56±12 mL/min, p<0.001) and CG (56±15 mL/min, 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 (mClcr and CG) in elderly individuals. This leads to dose calculation errors for many drugs, particularly in individuals with severe renal impairment. Thus, GFR-estimating equations 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 Scr 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.

Influence of Renal Function Estimation on Pharmacokinetic Modeling of Vancomycin in Elderly Patients

“…In particular, in this population of nonobese elderly patients with normal mean body weight, estimates provided by the CG equation were generally lower than those provided by the original MDRD and CKD-EPI equations, which is consistent with previous works from our group and many others (26)(27)(28)(29)(30)(31)(32). Because of this systematic difference, the use of the newer MDRD or CKD-EPI equation in place of the CG equation for drug dosing may have serious implications and cause overdosing in elderly patients for many drugs that are not monitored with concentration measurement (29,32,33).…”

Factors affecting the progression of renal dysfunction and the importance of salt restriction in patients with type 2 diabetic kidney disease

“…In addition, a significant difference between eGFR and Ccr measured through 24-hour urine collection at eGFR values less than 60 mL/min/1.73 m 2 was previously reported [21]. This difference between the eGFR and Ccr values was believed to be due to the fact that the concept of eGFR was originally developed for epidemiologic research and not for clinical evaluation of renal function in patients with altered renal function [22]. Furthermore, in a renal drug dose algorithm approved by the Food and Drug Administration, Ccr measured from 24-h urine collection is recommended for evaluating renal function rather than eGFR [23] although it is desirable to measure both markers to evaluate renal dysfunction in patients with CKD.…”

Rivaroxaban 10mg/d in severe renal failure does not prevent ischemic events in premorbid neurologic disease

“…Renal function should be estimated by calculating the creatinine-clearance by the Cockcroft-Gault-formula [1][2][3]. Other formulae may overestimate renal function (Table 1) [8,9].…”