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Kidney Function Influences Warfarin Responsiveness and Hemorrhagic Complications

Nita A. Limdi^*, T. Mark Beasley, Melissa F. Baird, Joyce A. Goldstein, Gerald McGwin^||, Donna K. Arnett^||, Ronald T. Acton^¶ and Michael Allon^**

Departments of ^* Neurology, Department of Biostatistics, Section on Statistical Genetics, Division of Hematology and Oncology, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, ^|| Department of Epidemiology, ^¶ Department of Microbiology, and ^** Division of Nephrology, University of Alabama at Birmingham, Alabama

Correspondence: Dr. Nita A. Limdi, Department of Neurology, University of Alabama at Birmingham, 1719 6th Avenue South, CIRC-312, Birmingham, AL 35294-0021. Phone: 205-934-4385; Fax: 205-996-9912; E-mail: nlimdi{at}uab.edu

Received for publication July 30, 2008. Accepted for publication November 13, 2008.

Although management of warfarin is challenging for patients with chronic kidney disease (CKD), no prospective studies have compared response to warfarin among patients with minimal, moderate, and severe CKD. This secondary analysis of a prospective cohort of 578 patients evaluated the influence of kidney function on warfarin dosage, anticoagulation control, and risk for hemorrhagic complications. We adjusted all multivariable regression and proportional hazard analyses for clinical and genetic factors. Patients with severe CKD (estimated GFR <30 ml/min per 1.73 kg/m²) required significantly lower warfarin dosages (P = 0.0002), spent less time with their international normalized ratio within the target range (P = 0.049), and were at a higher risk for overanticoagulation (international normalized ratio >4; P = 0.052), compared with patients with no, mild, or moderate CKD. Patients with severe CKD had a risk for major hemorrhage more than double that of patients with lesser degrees of renal dysfunction (hazard ratio 2.4, 95% confidence interval 1.1 to 5.3). In conclusion, patients with reduced kidney function require lower dosages of warfarin, have poorer control of anticoagulation, and are at a higher risk for major hemorrhage. These observations suggest that warfarin may need to be initiated at a lower dosage and monitored more closely in patients with moderate or severe CKD compared with the general population. Diminished renal function may have implications for a larger proportion of warfarin users than previously estimated.

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Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673