Implications of using modification of diet in renal disease versus Cockcroft-Gault equations for renal dosing adjustments.
OBJECTIVE
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 (CL(cr)) values of <30 mL/min/1.73 m(2) and underestimated the need for patients with a CL(cr) of >50 mL/min/1.73 m(2). 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).


CONCLUSIONS
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.
Moranville
Michael P
MP
Department of Pharmacy Services, Saint Joseph HealthCare, Lexington, KY, USA.
Jennings
Heath R
HR
D000368:Aged; D000369:Aged, 80 and over; D002985:Clinical Protocols; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism; D007677:Kidney Function Tests / Q000379:methods; D008875:Middle Aged; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D012189:Retrospective Studies
D004364:Pharmaceutical Preparations