title: Severe Endothelial Damage in Chronic Kidney Disease Patients Prior to Haemodialysis Vascular Access Surgery.
abstract: BACKGROUND
  Hemodialysis as an efficient therapy for advanced CKD is the most used treatment modality all over the world. Even though primary AVF is widely accepted as a best permanent vascular access in hemodialysis patients, up to 60% of all fistulas fail to mature. The pathogenesis of early fistula failure is not very well understood. Many general and local factors are involved: patient's age, sex, primary renal disease, small vessel's diameter, presence of accessory veins, prior venipunctures, surgical skill, genetics, etc. Histological investigations have confirmed the neointimal venous hyperplasia as a major pathological finding in stenotic lesions of AVF failure, due to local inflammation, oxidative stress and migration and proliferation of myofibroblasts, fibroblasts and endothelial cells.
  
  
  METHODS
  A total of 89 patients with stadium 4-5 of CKD are involved in the study. A typical radio-cephalic AVF is created in all patients. Part of the fistula vein was taken for histological, immunohistochemical (Vimentin, TGF β and KI67) and morphometric analysis. Appriopriate statistical method was applied.
  
  
  RESULTS
  Up to 80% of the patients showed some degree of endothelial changes at the time of creation of AVF, among them 19 pts with substantial intimal hyperplasia, 51 with medial hypertrophy and 19 pts with normal histology. Almost two thirds of the patients did not have expression of TGFβ. More than 95% had some expression of Vimentin. None of the patients had expression of the marker KI 67.
  
  
  CONCLUSIONS
  Medial hypertrophy is predominant preexisting pathohistological lesion prior the AVF creation, despite the presence of neointimal hyperplasia. The absence of TGFβ expression in majority of our patients could suggest that inflammation and oxidative stress are developing later, after vascular access surgery. The dominant cells within the stenosis in the veins are myofibroblasts. Their increased presence maybe a reason why some patients are prone to developing venous endothelial changes as a results of exaggerated vascular endothelial response to the effect of uremia, hypertension and other insults.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Pushevski
authors.forename: Petar
authors.initials: P
authors.lastname: Dejanov
authors.forename: Vesna
authors.initials: V
authors.lastname: Gerasimovska
authors.forename: Gordana
authors.initials: G
authors.lastname: Petrushevska
authors.forename: Angel
authors.initials: A
authors.lastname: Oncevski
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Sikole
authors.forename: Zivko
authors.initials: Z
authors.lastname: Popov
authors.forename: Ninoslav
authors.initials: N
authors.lastname: Ivanovski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D015415:Biomarkers / Q000032:analysis; D042783:Endothelial Cells / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D006984:Hypertrophy; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D058426:Neointima; D011446:Prospective Studies; D017534:Radial Artery / Q000601:surgery*; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy*; D012307:Risk Factors; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000032:analysis; D017211:Treatment Failure; D014680:Veins / Q000737:chemistry / Q000473:pathology* / Q000601:surgery*; D014746:Vimentin / Q000032:analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019394:Ki-67 Antigen; D016212:Transforming Growth Factor beta; D014746:Vimentin