Cyclosporine is associated with endothelial dysfunction but not with platelet activation in renal transplantation

Background: Cyclosporine (CsA) is associated with thrombotic micro-angiopat hy and endothelial dysfunction. Markers of endothelial dysfunction may serv e to identify patients at risk for development of vascular injury. In this study we measured von Willebrand Factor (vWF) and sP-selectin as possible m arkers for endothelial dysfunction in renal transplant recipients at differ ent concentrations of CsA. Because sP-selectin can also be derived from pla telets an additional in vitro study was performed to study the potential ef fect of CsA on the expression of P-selectin on platelet surface, while the effects of CSA on the interaction of platelets with Endothelial Cell Matrix (ECM) were studied under flow conditions in a perfusion chamber model. Met hods: CsA was stepwisely replaced by mycophenolate mofetil (MMF) in 15 rena l transplant recipients (more than 6 months after transplantation). VWF and sP-selectin were measured at normal CsA (median trough level 130 mug/l), l ow CsA (trough level 45 mug/l) and after stopping CsA. MMF 2 g daily was ad ded while lowering and stopping CsA. Platelet activation was investigated b y measurement of P-selectin on platelet surface by flow-cytometry (FACS), a fter incubation with CsA (0, 2, 20 and 200 mg/l) in vitro and after perfusi on of whole blood over ECM with CsA (0 or 2 mg/l, peak levels). Results: St epwise withdrawal of CsA gave a dose-related decrease of both vWF and sP-se lectin, suggesting reversible endothelial dysfunction. FACS showed no expre ssion of P-selectin on platelets by CsA. Also perfusion studies over ECM de monstrated no platelet activation by CsA but even inhibition of platelet ad hesion and aggregation. Conclusions: The use of CsA is not accompanied by p latelet activation. However endothelial dysfunction induced by CsA does occ ur as reflected by increased vWF and sP-selectin. (See Editorial p. 1). (C) 2001 Elsevier Science BY All rights reserved.