title: Kidney function influences warfarin responsiveness and hemorrhagic complications.
abstract: 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.
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, 1719 6th Avenue South, CIRC-312, Birmingham, Alabama 35294-0021, USA. nlimdi@uab.edu
authors.forename: Nita A
authors.initials: NA
authors.lastname: Limdi
authors.forename: T Mark
authors.initials: TM
authors.lastname: Beasley
authors.forename: Melissa F
authors.initials: MF
authors.lastname: Baird
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Goldstein
authors.forename: Gerald
authors.initials: G
authors.lastname: McGwin
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Acton
authors.forename: Michael
authors.initials: M
authors.lastname: Allon
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D001806:Blood Urea Nitrogen; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006470:Hemorrhage / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000145:classification / Q000188:drug therapy* / Q000503:physiopathology*; D007677:Kidney Function Tests; D008875:Middle Aged; D018579:Patient Selection; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012307:Risk Factors; D012720:Severity of Illness Index; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D003404:Creatinine