title: Does the endothelial function change in renal transplant patients with longer duration of exposure and with higher cumulative doses of cyclosporine?
abstract: OBJECTIVE
  Administration of cyclosporine (CsA) is one potential cause of endothelial dysfunction in renal transplant patients. We sought to investigate endothelial functional changes with respect to the cumulative dose and duration of exposure to CsA.
  
  
  METHODS
  Sixty-six renal recipients and 25 healthy controls were included in the study. The recipients were classified according to their time of CsA exposure: group 1 (0 to 36 months); group 2 (36 to 72 months); and group 3 (over 72 months). Endothelial function of the brachial artery was evaluated using high-resolution vascular ultrasound. Endothelium-dependent and -independent vasodilatation (EDD and EID, respectively) were assessed by assessing the responses to reactive hyperemia and using sublingual isosorbide dinitrate (ISDN), respectively.
  
  
  RESULTS
  There were no statistically significant differences between the groups with regard to their demographic, clinical, and most biochemical characteristics. Baseline measurements of the diameter of the brachial artery were similar in all groups. The values of mean brachial artery EDD and EID responses in groups 1, 2, and 3 were less than those in the control group (P < .05, P < .05, and P < .05, respectively). Mean brachial artery EDD and EID in group 1 were significantly impaired compared to groups 2 and 3 (for EDD: P < .05 and P < .05, respectively; for EID: P < .05 and P < .05, respectively). In contrast there was no difference between groups 2 and 3 with respect to these parameters. There were mild to moderate positive correlations between the cumulative doses of CsA and EDD and EID (r = .26 and r = .52, P < .05, respectively).
  
  
  CONCLUSIONS
  Endothelial dysfunction was more prominent in the first 36-month period than later despite the longer exposure to and higher cumulative doses of CsA. This finding may reflect an extended effect of the uremic state on endothelial function or more intense doses of CsA in early posttransplant period.
authors.affiliation: Department of Cardiology, Nephrology, Capa, Istanbul, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Mercanoglu
authors.forename: H
authors.initials: H
authors.lastname: Oflaz
authors.forename: A
authors.initials: A
authors.lastname: Turkmen
authors.forename: O
authors.initials: O
authors.lastname: Kocaman
authors.forename: B
authors.initials: B
authors.lastname: Bunyak
authors.forename: S
authors.initials: S
authors.lastname: Umman
authors.forename: E
authors.initials: E
authors.lastname: Yekeler
authors.forename: E
authors.initials: E
authors.lastname: Kasikcioglu
authors.forename: M
authors.initials: M
authors.lastname: Meric
authors.forename: S
authors.initials: S
authors.lastname: Demirel
authors.forename: M
authors.initials: M
authors.lastname: Kucuk
authors.forename: M S
authors.initials: MS
authors.lastname: Sever
mesh_terms: D000328:Adult; D001806:Blood Urea Nitrogen; D016572:Cyclosporine / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D012016:Reference Values; D012044:Regression Analysis; D013997:Time Factors; D014511:Uremia / Q000139:chemically induced / Q000453:epidemiology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine