title: The effect of calcineurin inhibitors on endothelial and platelet function in renal transplant patients.
abstract: OBJECTIVE
  Posttransplant cardiovascular mortality is still an important problem in renal transplant patients. In addition to conventional coronary risk factors, coagulation abnormalities play a key role in the hypercoagulable state observed in transplanted patients. Though renal transplantation eliminates cardiovascular disease risk factors by restoring renal function, it introduces new cardiovascular risks derived, in part from immunosupressive medications. We aimed to assess the effect of calcineurin inhibitors on endothelial function, platelet activation and aggregation in renal transplant patients.
  
  
  METHODS
  62 renal transplant were studied. Staging was performed according to immunosuppression regimen. Group 1 (n = 37) were treated with cyclosporine/mycophenolate mofetil/methylprednisolone and Group 2 (n = 25) were treated with tacrolimus/mycophenolate mofetil/methylprednisolone. The control group consisted of 16 healthy subjects (Group 3). Hematological and biochemical tests, asymmetric dimethyl arginine (ADMA), sP-selectin levels and platelet aggregation tests were studied.
  
  
  RESULTS
  ADMA levels were higher in Group1 and statistically significant differences were observed compared with those of Group 2 and Group 3 (p < 0.05). Platelet aggregation values induced by all agonists (Adenosine diphosphate (ADP), epinephrine, ristocetin, collagen) were lower in Group 1 than Group 2 and Group 3, but the difference did not reach statistical significance (p > 0.05). There was a negative correlation between cyclosporine level and platelet aggregation values induced by ADP (r = -0.43, p < 0.01), ristocetin (r = -0.40, p < 0.05), epinephrine (r = -0.41, p < 0.05), and collagen (r = -0.43, p < 0.01). sP-selectin levels were appreciably higher in Group 1 and statistically significant differences were observed compared with those of Group 2 (p < 0.05) and Group 3 (p < 0.01).
  
  
  CONCLUSIONS
  The results of our study suggest that CsA induces platelet activation without inducing platelet aggregation. Endothelial dysfunction due to vascular endothelial damage reflected by increases in ADMA values may increase the tendency for thrombotic events in patients who had undergone renal transplantation.
authors: Eskisehir Osmangazi University Medical School, Eskisehir, Turkey. gsahin@ogu.edu.tr
authors: G
authors: G
authors: Sahin
authors: O M
authors: OM
authors: Akay
authors: C
authors: C
authors: Bal
authors: A U
authors: AU
authors: Yalcin
authors: Z
authors: Z
authors: Gulbas
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D019007:P-Selectin; C018524:N,N-dimethylarginine; D016572:Cyclosporine; D001120:Arginine; D019001:Nitric Oxide Synthase; D009173:Mycophenolic Acid; D016559:Tacrolimus