title: Fibrinolysis defect in long-term hemodialysis patients with type 2 diabetes mellitus and its relation to metabolic disorders.
abstract: OBJECTIVE
  Patients with chronic renal failure (CRF) secondary to diabetes mellitus show a high incidence of atherosclerosis with its thrombotic complications. Both CRF and type 2 diabetes mellitus (DM2) results in fibrinolysis defects causally related to atherogenesis and thrombogenesis. It is not well known whether or not and, if so, how fibrinolysis is altered in patients with both CRF and DM2. Our study was designed (1) to identify the fibrinolysis defect present in patients with DM2-mediated CRF and treated by long-term hemodialysis (DM2HD), and (2) to establish whether the fibrinolysis defect is related to the metabolic abnormalities observed in CRF or DM2.
  
  
  METHODS
  Sixteen DM2HD patients and 23 healthy individuals (HI) had their euglobulin clot lysis time (ECLT), and tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) activities (act) and concentrations (ag) assessed before and after standard fibrinolytic stimulus (i.v. administration of 0.4 microg/kg BW 1-deamino-8-D-arginine vasopressin, DDAVP) along with metabolic status markers.
  
  
  RESULTS
  DDAVP caused a significant shortening of ECLT, rises in tPA act and ag, and a significant decrease in PAI-1 act. PAI-1 ag declined significantly in HI, but not in DM2HD. A comparison of responses to DDAVP revealed the groups differed significantly in the change in PAI-1 ag. Whereas, in HI, PAI-1 ag decreased by 11.8 ng/ml, no decrease was seen in DM2HD (0.0 ng/ml) (p < 0.0001; medians given; unpaired Wilcoxon's test). Stepwise regression analysis showed the change in PAI-1 ag was highly group-specific (DM2HD vs. HI, regression coefficient 21.22; partial correlation 0.58; p < 0.0001) and, also dependent on the serum concentrations of apolipoprotein A-I (-32.41; -0.46; p < 0.01) and homocysteine (0.35; 0.36; p < 0.05).
  
  
  CONCLUSIONS
  Patients with type 2 DM and CRF on long-term hemodialysis have a fibrinolysis defect manifesting itself after standard fibrinolytic stimulus by an insufficient decrease in PAI-1 concentrations. The defect is related to decreased serum levels of apolipoprotein A-I and increased serum levels of homocysteine. The defect might be a factor contributing to accelerated atherosclerosis and thrombotic complications in these patients.
authors.affiliation: Department of Internal Medicine I, Charles University Medical School, Pilsen, Czech Republic. opatrny@fnplzen.cz
authors.forename: Karel
authors.initials: K
authors.lastname: Opatrný
authors.forename: Pavlína
authors.initials: P
authors.lastname: Zemanová
authors.forename: Jan
authors.initials: J
authors.lastname: Mares
authors.forename: Lasislav
authors.initials: L
authors.lastname: Vít
authors.forename: Sylvia
authors.initials: S
authors.lastname: Opatrná
authors.forename: Frantisek
authors.initials: F
authors.lastname: Sefrna
authors.forename: Václav
authors.initials: V
authors.lastname: Hejda
authors.forename: Martina
authors.initials: M
authors.lastname: Tomsů
authors.forename: Jaromír
authors.initials: J
authors.lastname: Eiselt
authors.forename: Shaul G
authors.initials: SG
authors.lastname: Massry
mesh_terms: D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D003894:Deamino Arginine Vasopressin; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood*; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D006435:Renal Dialysis; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D017395:Plasminogen Activator Inhibitor 1; D006710:Homocysteine; D010959:Tissue Plasminogen Activator; D003894:Deamino Arginine Vasopressin