title: The impact of antiproteinuric therapy on the prothrombotic state in patients with overt proteinuria.
abstract: BACKGROUND
  Overt proteinuria is a strong risk factor for thromboembolism, owing to changes in the levels of various coagulation proteins and urinary antithrombin loss. The described coagulation disturbances in these patients are based on outdated studies conducted primarily in the 1970s and 1980s. Whether these coagulation disturbances resolve with antiproteinuric therapy has yet to be studied.
  
  
  METHODS
  A total of 32 patients with overt proteinuria (median, 3.7 g day(-1) ; interquartile range, 1.5-5.6) were enrolled in this intervention crossover trial designed to assess optimal antiproteinuric therapy with sodium restriction, losartan, and diuretics. Levels of various procoagulant and anticoagulant proteins, and parameters of two thrombin generation assays (calibrated automated thrombogram [CAT] and prothrombin fragment 1 + 2) were compared between the placebo period and the maximum antiproteinuric treatment period. As a secondary analysis, coagulation measurements of the placebo period in these patients were compared with those of 32 age-matched and sex-matched healthy controls.
  
  
  RESULTS
  Median proteinuria was significantly lower during the maximum treatment period (median, 0.9 g day(-1) ; interquartile range, 0.6-1.4; P < 0.001) than during the placebo period. Similarly, levels of various liver-synthesized procoagulant and anticoagulant proteins, activated protein C resistance and prothrombin fragment 1 + 2 levels were significantly lower during the maximum treatment period than during the placebo period. However, von Willebrand factor and factor VIII levels were similar. On the basis of the higher levels of procoagulant proteins (fibrinogen, FV, FVIII, and von Willebrand factor) and both thrombin generation assays, patients were substantially more prothrombotic than healthy controls (P < 0.004).
  
  
  CONCLUSIONS
  Antiproteinuric therapy ameliorates the prothrombotic state. Proteinuric patients are in a more prothrombotic state than healthy controls.
authors.affiliation: Division of Hemostasis and Thrombosis, Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands. b.k.mahmoodi@int.umcg.nl
authors.forename: B K
authors.initials: BK
authors.lastname: Mahmoodi
authors.forename: A B
authors.initials: AB
authors.lastname: Mulder
authors.forename: F
authors.initials: F
authors.lastname: Waanders
authors.forename: H M H
authors.initials: HM
authors.lastname: Spronk
authors.forename: R
authors.initials: R
authors.lastname: Mulder
authors.forename: M C J
authors.initials: MC
authors.lastname: Slagman
authors.forename: L
authors.initials: L
authors.lastname: Vogt
authors.forename: G
authors.initials: G
authors.lastname: Navis
authors.forename: H
authors.initials: H
authors.lastname: Ten Cate
authors.forename: H C
authors.initials: HC
authors.lastname: Kluin-Nelemans
authors.forename: G D
authors.initials: GD
authors.lastname: Laverman
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011507:Proteinuria / Q000150:complications / Q000188:drug therapy*; D011516:Prothrombin / Q000378:metabolism*; D013927:Thrombosis / Q000150:complications*
chemical_list: D010919:Placebos; D011516:Prothrombin; D019808:Losartan