Original InvestigationPathogenesis and Treatment of Kidney DiseaseWarfarin Dosing in Patients With Impaired Kidney Function
Section snippets
University of Alabama at Birmingham Cohort
The Pharmacogenetic Optimization of Anticoagulation Therapy (POAT) and the Genetic and Environmental Determinants of Warfarin (GEDWR) are ongoing prospective cohort studies aimed at defining the influence of polymorphisms in CYP2C9 and other genes on warfarin response. Patients 20 years and older were considered eligible if the intended duration of anticoagulation therapy was 2 years or longer, therapy was managed at the anticoagulation clinic, and international normalized ratio (INR) was 2-3.
Results
Of 797 eligible participants at the UAB (UAB cohort), 76 (9.5%) declined participation in the study and 13 were excluded because of missing serum creatinine values. The remaining 708 participants (mean age, 61 ± 15 years; 50.0% men) formed the UAB cohort (327 African Americans, 377 European Americans, 3 Hispanics, and 1 Asian). Of 303 eligible participants at UIC, 31 (10.2%) declined participation. The UIC cohort (n = 272) was composed of 207 African American, 23 European American, and 42
Discussion
The influence of kidney function on disposition of drugs excreted by the kidney is widely recognized and used to derive dosing reductions in patients with kidney impairment. However, there now is increasing appreciation that kidney impairment can also decrease nonrenal clearance and alter the bioavailability of and response to drugs predominantly metabolized by the liver.8, 24 The present study shows that dose requirement for warfarin, a drug primarily metabolized by the hepatic CYP450 system,
Acknowledgements
The authors thank Dr Joyce Goldstein and Joyce Blaisdell for work with CYP2C9 genotyping; the patients who participated in the study; Janice Ware, Joseph Huffstutler, Roberta Hill, Alison Del Carmen, Edith Nutescu, and Nancy Shapiro for untiring efforts with patient recruitment; the staff of the Anticoagulation Clinic at The Kirklin Clinic, Cooper Green Hospital, and Jefferson Clinic PC for help with identification of potential participants; the physicians, especially Drs Mark Wilson and
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Originally published online as doi:10.1053/j.ajkd.2010.05.023 on August 16, 2010.