title: Warfarin therapy that results in an International Normalization Ratio above the therapeutic range is associated with accelerated progression of chronic kidney disease.
abstract: OBJECTIVE
  We had previously reported that acute kidney injury (AKI) in warfarin-treated chronic kidney disease (CKD) patients may occur shortly after an acute increase in the International Normalization Ratio (INR) >3.0 with formation of occlusive red blood casts. Recovery from this warfarin-associated AKI is poor. Here we investigated whether excessive warfarin therapy could accelerate the progression of CKD.
  
  
  METHODS
  We analyzed serum creatinine (SC) and INR in 103 consecutive CKD patients on warfarin therapy in our Nephrology program from 2005 to the present.
  
  
  RESULTS
  Forty-nine patients experienced at least 1 episode of INR >3.0. Of these, 18 patients (37%, Group 1) developed an unexplained increase in SC > or =0.3 mg/dl coincident with INR >3.0 (mean SC increase 0.61 +/- 0.44 mg/dl); 31 patients (63%, Group 2) showed stable SC (mean SC change 0.04 +/- 0.19 mg/dl). Subsequent CKD progression was accelerated in Group 1, but not in Group 2. The 2 groups were not different with respect to demographics, comorbidities, blood pressure, or therapies. However, African Americans were overrepresented in Group 1 (p = 0.035).
  
  
  CONCLUSIONS
  Overanticoagulation is associated with faster progression of CKD in a high percentage of patients. Our results indicate the need for prospective trials. Nevertheless, we suggest that our findings are sufficiently compelling at this point to justify extra caution in warfarin-treated CKD patients to avoid overanticoagulation.
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA. sergey.brodsky@osumc.edu
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Brodsky
authors.forename: Michael
authors.initials: M
authors.lastname: Collins
authors.forename: Edward
authors.initials: E
authors.lastname: Park
authors.forename: Brad H
authors.initials: BH
authors.lastname: Rovin
authors.forename: Anjali A
authors.initials: AA
authors.lastname: Satoskar
authors.forename: Gyongyi
authors.initials: G
authors.lastname: Nadasdy
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wu
authors.forename: Udayan
authors.initials: U
authors.lastname: Bhatt
authors.forename: Tibor
authors.initials: T
authors.lastname: Nadasdy
authors.forename: Lee A
authors.initials: LA
authors.lastname: Hebert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D006801:Humans; D019934:International Normalized Ratio / Q000639:trends; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D014859:Warfarin; D003404:Creatinine