title: Chronic renal failure is accompanied by endothelial activation and a large increase in microparticle numbers with reduced procoagulant capacity.
abstract: BACKGROUND
  In patients with chronic renal failure (CRF), cardiovascular disease is the leading cause of increased morbidity and mortality. We hypothesized a role for endothelial activation and microparticle (MP) numbers and procoagulant activity in the pre-thrombotic state of these patients.
  
  
  METHODS
  We analysed blood samples of 27 patients with CRF [8 chronic kidney disease Stage 4 (CKD4), 9 peritoneal dialysis (PD) and 10 haemodialysis (HD), samples taken before and after HD] and 10 controls. Degree and nature of endothelial activation were assessed by measuring mature von Willebrand factor (vWF) and vWF propeptide levels. Cellular MPs were characterized by flow cytometry and MP-specific thrombin generation (TG) measurements.
  
  
  RESULTS
  CRF was accompanied by chronic (CKD4 and PD) or acute (HD) endothelial activation. Patients with CRF had substantially higher MP numbers than controls (median 9400 versus 4350×10(6)/L, P=0.001), without significant differences between the treatment subgroups or between pre- and post-HD. The vast majority of MPs were platelet derived. Of the minor populations, endothelial MPs and tissue factor-bearing MPs were more abundant in CRF. MPs were procoagulant, but the increase in numbers was not reflected in a proportional increase in MP-specific TG.
  
  
  CONCLUSIONS
  Renal failure is accompanied by endothelial activation of a different nature in CKD4 and PD patients compared to HD patients, and results in all subgroups in an increase of mainly platelet-derived MPs that appear to be less procoagulant than in other disease states, possibly because of the uraemic functional defect of their cellular source.
authors.affiliation: Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands. mctrappenburg@gmail.com
authors.forename: Marijke C
authors.initials: MC
authors.lastname: Trappenburg
authors.forename: Muriel
authors.initials: M
authors.lastname: van Schilfgaarde
authors.forename: Fenneke C P
authors.initials: FC
authors.lastname: Frerichs
authors.forename: Henri M H
authors.initials: HM
authors.lastname: Spronk
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Carola W H
authors.initials: CW
authors.lastname: de Fijter
authors.forename: Wim E
authors.initials: WE
authors.lastname: Terpstra
authors.forename: Anja
authors.initials: A
authors.lastname: Leyte
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000209:etiology / Q000473:pathology; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000473:pathology*; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D006435:Renal Dialysis; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor; D013925:Thromboplastin; D013917:Thrombin