title: Overanticoagulation is associated with renal function decline.
abstract: BACKGROUND
  Recent studies suggest that overanticoagulation impairs renal function in patients on warfarin therapy, due to renal tubular obstruction from glomerular hemorrhage.
  
  
  METHODS
  Data from the Rotterdam Study (The Netherlands), a prospective population-based cohort study of patients 55 years and older, were used for this study. Information on vitamin K antagonist (VKA) therapy was obtained from the regional anticoagulation clinic, where prothrombin times were monitored every 1-6 weeks depending on target level and stability of the international normalized ratio (INR). Linear regression was performed to study the association between the cumulative number of instances of overanticoagulation (defined as a measurement of an INR >6.0) and the change in renal function between baseline and third examination round based on estimated glomerular filtration rate (CKD-EPI equation). Age, sex, baseline renal function, baseline and incident heart failure, and indication for VKA therapy were included as potential confounders.
  
  
  RESULTS
  Information was available for analysis on 2,802 study participants in whom overanticoagulation was significantly associated with a decline in renal function, after adjustment for confounding by age, sex, heart failure, baseline glomerular filtration rate and indication for VKA therapy (-0.180 ml/min per 1.73 m(2) per year per event for INR >6.0, p = 0.030).
  
  
  CONCLUSIONS
  Overanticoagulation (INR >6.0) is associated with a decline in renal function. Further studies are needed to evaluate the causal role of different degrees of overanticoagulation, including transient effects, in high-risk groups, and the association with the new oral anticoagulants.
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Jan Cornelis
authors.initials: JC
authors.lastname: van Blijderveen
authors.forename: Katia M
authors.initials: KM
authors.lastname: Verhamme
authors.forename: Robert
authors.initials: R
authors.lastname: Zietse
authors.forename: Loes E
authors.initials: LE
authors.lastname: Visser
authors.forename: Silvana A
authors.initials: SA
authors.lastname: Romio
authors.forename: Peter N
authors.initials: PN
authors.lastname: Buhre
authors.forename: Miriam C
authors.initials: MC
authors.lastname: Sturkenboom
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Straus
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D062787:Drug Overdose; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D019934:International Normalized Ratio; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin