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Comparative Study
. 2009 Jul;54(1):33-42.
doi: 10.1053/j.ajkd.2009.03.008. Epub 2009 May 17.

Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations

Lesley A Stevens  1 , Thomas D Nolin, Michelle M Richardson, Harold I Feldman, Julia B Lewis, Roger Rodby, Raymond Townsend, Aghogho Okparavero, Yaping Lucy Zhang, Christopher H Schmid, Andrew S Levey; Chronic Kidney Disease Epidemiology Collaboration
Collaborators, Affiliations
Comparative Study

Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations

Lesley A Stevens et al. Am J Kidney Dis. 2009 Jul.

Abstract

Background: Kidney disease alters the pharmacokinetic disposition of many medications, requiring dosage adjustment to maintain therapeutic serum concentrations. The Cockcroft-Gault (CG) equation is used for pharmacokinetic studies and drug dosage adjustments, but the Modification of Diet in Renal Disease (MDRD) Study equation is more accurate and more often reported by clinical laboratories than the CG equation.

Study design: Diagnostic test study.

Settings & participants: Pooled data set for 5,504 participants from 6 research studies and 4 clinical populations with measured glomerular filtration rate (GFR).

Index test: Estimated kidney function using the MDRD Study and CG equations incorporating actual (CG) or ideal body weight (CG(IBW)) and standardized serum creatinine concentrations.

Reference test: Measured GFR assessed by using iodine-125-iothalamate urinary clearance.

Outcome: Concordance of assigned kidney function categories designated by the Food and Drug Administration (FDA) Guidance for Industry for pharmacokinetic studies and recommended dosages of 15 medications cleared by the kidneys.

Results: Concordance of kidney function estimates with measured GFR for FDA-assigned kidney function categories was 78% for the MDRD Study equation compared with 73% for the CG equation (P < 0.001) and 66% for the CG(IBW) equation (P < 0.001). Concordance between the MDRD Study equation and CG and CG(IBW) equations was 78% and 75%, respectively (P < 0.001). Concordance of kidney function estimates with measured GFR for recommended drug dosages was 88% for MDRD Study equation compared with 85% for the CG equation (P < 0.001) and 82% for the CG(IBW) equation (P < 0.001), with lower concordance when dosing recommendations for drugs included narrow GFR ranges. Concordance rates between the CG and CG(IBW) equations and MDRD Study equation were 89% and 88%, respectively (P < 0.05).

Limitations: Results based on simulation rather than pharmacokinetic studies. Outcome was drug dosage recommendations, rather than observed drug efficacy and safety.

Conclusions: The MDRD Study equation can also be used for pharmacokinetic studies and drug dosage adjustments. As more accurate GFR-estimating equations are developed, they should be used for these purposes.

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Figures

Figure 1
Figure 1. Concordance of Modification of Diet in Renal Disease (MDRD) Study, Cockcroft-Gault (CG), and the Cockcroft-Gault adjusted for ideal body weight (CGIBW) equations with measured GFR for assignment of kidney function categories by patient subgroup
Each bar indicates percentage concordance to measured glomerular filtration rate (GFR) for each of the 43 different equations. A) Age (< 40, 40–65, > 65 years). (B) Sex. (C) Race (African American or other; White; Asian; Native American, Hispanic, or Pacific Islander). (D) Weight (< 60, 60–90, > 90 kg); (E) Presence or absence of diabetes. (F) Presence or absence of kidney transplant. Rate of concordance to measured GFR for CG and CGIBW was significantly different (p-value < 0.001) from the concordance to measured GFR for the MDRD Study equation for all subgroups except weight 60–90 kg (CG), weight >90 kg (CGIBW), diabetes (CG), and transplant recipients (CGIBW).
Figure 2
Figure 2. Concordance of Cockcroft-Gault (CG) and Cockcroft-Gault adjusted for ideal body weight (CGIBW) with the Modification of Diet in Renal Disease (MDRD) Study equation for assignment of kidney function categories by patient subgroups
Each bar indicates percentage concordance to MDRD Study equation for the two equations. (A) Age (<40, 40–65, > 65 years). (B) Sex. (C) Race (African American or other; White; Asian; Native American, Hispanic, or Pacific Islander). (D) Weight (< 60, 60–90, > 90 kg); (E) Presence or absence of diabetes. (F) Presence or absence of kidney transplant. *p-value < 0.0001 for comparisons of each equation to MDRD study equation for each subgroup
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Comment in

References

    1. Food and Drug Administration. Guidance for Industry: Pharmacokinetics in Patients with Impaired Renal Function — Study Design, Data Analysis, and Impact on Dosing and Labeling. Rockville: U.S. Department of Health and Human Services; 1998. May,
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