Effect of impaired renal function on the maintenance dose of warfarin in Japanese patients

Background: Chronic kidney disease (CKD) alters dose-effect relationship not only of drugs eliminated by the kidney but also of some drugs metabolized by the liver and not renally excreted. It is not known whether impaired renal function alters dose-effect relationship of warfarin in Asian patients. It is also unknown whether the maintenance dose of warfarin can be predicted more accurately by incorporating renal function in Asians. Methods: This was a cross-sectional study of patients receiving constant doses of warfarin who had PT-INR within 1.5-3.0 for 3 months or longer. Results: In a total of 137 participants, the estimated creatinine clearance (eCrCI) was 62.5 +/- 25.5 [ml/ min] and the warfarin dose was 3.21 +/- 1.46 [mg/day] (both mean +/- standard deviation). There was a significant correlation between warfarin dose and eCrCI (p < 0.0001, r(2) = 0.23). In a stepwise linear regression with the maintenance dose of warfarin as the dependent variable, eCrCI as well as age, body weight, intra-individual average prothrombin time/international normalized ratio (PT-INR), and genotype of VKORC1 -1639 G>A polymorphism were chosen as independent variables. The coefficient of determination (r(2)) of this formula was 0.47. A regression equation with all the same explanatory variables except for eaCrCI had an r(2) of 0.41. Conclusions: The maintenance warfarin dose was positively correlated with kidney function as represented by eCrCI in Japanese patients. Incorporating eCrCI improved accuracy of predicting warfarin maintenance dose in this population. (C) 2014 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.