Evaluation of warfarin dose requirements in patients with chronic kidney disease and end-stage renal disease.
OBJECTIVE
The effect of chronic kidney disease (CKD) on warfarin has gained attention because of an increased risk of thromboembolism and an increased risk of bleeding associated with warfarin treatment in these patients. Data suggest that patients with reduced kidney function require lower warfarin doses; however, relatively few patients with end-stage renal disease (ESRD) were included in previous studies. The goal of this study was to evaluate warfarin dosing requirements and time to reach therapeutic international normalized ratio (INR) in patients with CKD stages 3-5 and ESRD compared with patients with normal kidney function (NKF).


METHODS
A historical cohort was identified to evaluate warfarin response in 210 hospitalized adults with varying degrees of kidney function initiated or maintained on warfarin for 4 or more consecutive days including 49 patients with NKF (glomerular filtration rate [GFR] higher than 60 ml/min/1.73 m(2) ), 44 with CKD stage 3, 27 with CKD stage 4/5, and 90 with ESRD. The average daily dose (ADD), time to achieve a therapeutic INR, and adverse effects were compared.


RESULTS
The ADD to maintain a therapeutic INR was 5.6 ± 1.7 mg in the NKF group, 4.3 ± 1.6 mg in CKD stage 3, 4.6 ± 1.9 mg in CKD stage 4/5, and 4.8 ± 1.9 mg in ESRD. The ADD was lower in CKD/ESRD patients compared with NKF patients (p=0.001), especially among whites. The time to reach a therapeutic INR in patients newly initiated on warfarin was significantly lower in the CKD/ESRD group when compared with the NKF group (p=0.02). No differences in bleeding episodes were observed during hospitalization or within 30 days of discharge in patients with CKD stage 3 or higher compared with patients with NKF.


CONCLUSIONS
Our findings suggest that CKD and ESRD patients require ~20% lower warfarin doses to maintain a therapeutic INR and may require less time to achieve a therapeutic INR compared with patients with NKF.
Department of Pharmacy, Methodist University Hospital, Memphis, Tennessee.
Sami A
SA
Sakaan
Joanna Q
JQ
Hudson
Carrie S
CS
Oliphant
Elizabeth A
EA
Tolley
Carolyn
C
Cummings
Numan A
NA
Alabdan
Timothy H
TH
Self
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation / Q000379:methods; D005260:Female; D006760:Hospitalization / Q000639:trends; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D014859:Warfarin
INR; anticoagulation; chronic kidney disease; end-stage renal disease; warfarin