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MICHAEL P. MORANVILLE, PHARM.D., is Postgraduate Year 2 Cardiology Resident, Department of Pharmacy Services, University of North Carolina Hospitals, Chapel Hill; at the time of writing he was Postgraduate Year 1 Pharmacy Resident, Department of Pharmacy Services, Saint Joseph HealthCare, Lexington, KY. HEATH R. JENNINGS, PHARM.D., BCPS, is Director of Pharmacy Acute Care Services, Department of Pharmaceutical Services, University of Chicago Medical Center, Chicago, IL.

Address correspondence to Dr. Jennings at the Department of Pharmaceutical Services, University of Chicago Medical Center, 5841 South Maryland Avenue, MC0010 Room TE026, Chicago, IL 60637-1470 (heath.jennings{at}uchospitals.edu).

Purpose. The drug-dosing implications of using modification of diet in renal disease (MDRD) versus Cockcroft–Gault equations were analyzed. Methods. This retrospective, cohort-controlled study evaluated the implications of using MDRD versus Cockcroft–Gault equations for renal dosing adjustments in patients with stage III–V chronic kidney disease. Dosing simulations were completed for each patient using both MDRD and Cockcroft–Gault methods and then compared to published manufacturer dosing recommendations. Bland-Altman analysis assessed agreement of MDRD and Cockcroft–Gault estimates. Contingency tables were used to evaluate the clinical relevance of dosing adjustments in terms of medication overdoses and underdoses. Results. Data from 4698 patients with stage III–V chronic kidney disease were analyzed. Use of the MDRD equation overestimated the need for dosing adjustments for patients with creatinine clearance (CLcr) values of <30 mL/min/1.73 m2 and underestimated the need for patients with a CLcr of >50 mL/min/1.73 m2. For medication-dosing thresholds, MDRD was associated with an underdose rate of 7.3% and an overdose rate of 9.6% (p < 0.01 for both). For MDRD adjustments within medication-dosing ranges, both overdoses and underdoses occurred in up to 12.4% (p < 0.01). Total dosing errors for MDRD ranged from 9.8% to 18.2%, depending on the medication (p < 0.01). Conclusion. Significant variability exists between the MDRD and Cockcroft–Gault equations for spot dosing adjustments. Use of MDRD estimates with current manufacturer dosing guidelines may result in subtherapeutic medication therapies for patients with stage IV or V disease and supratherapeutic therapies for patients with stage III disease. Index terms: Dosage; Errors, medication; Kidney diseases; Methodology; Protocols