Impact of Immunosuppressive Treatment on Endothelial Biomarkers After Kidney Transplantation

Abstract

Endothelial dysfunction occurs in hemodialysis and kidney-transplanted patients and can be enhanced by immunosuppressive therapy. Circulating endothelial cells (CEC), endothelial microparticles (EMP) and sVCAM-1 provide information on endothelium activation and damage.We compared the impact of two immunosuppressive regimens (CsA/Aza vs. Tac/MMF) on the kinetics of CEC, EMP and sVCAM-1 levels in 52 patients, both before graft and 3, 6, 9 and 12 months after graft, in reference to 50 healthy controls.CEC, EMP and sVCAM-1 levels were significantly decreased 1 year after transplantation (M12) as compared to pretransplant values. At M12, CEC and sVCAM-1 levels were significantly higher than those of controls whereas EMP reached normal values. Nine months postgraft, lower CEC and normalized EMP levels were found in patients receiving cyclosporine microemulsion/ azathioprine (CsA/Aza) when compared to patients treated with tacrolimus/ mycophenolate mofetil (Tac/MMF). Multivariate analysis evidenced positive correlations between CEC and history of cardiovascular diseases and between EMP and cytomegalovirus infection at M12.In conclusion, our combined analysis of endothelial injury markers confirms the favorable impact of renal transplantation on endothelium, and show that CEC levels discriminate treatment-associated endothelial toxicity. These results enlighten the potential of these noninvasive blood biomarkers in indexing vascular injury and optimize therapeutic options.

Early posttransplant changes in circulating endothelial microparticles in patients with kidney transplantation

“…Long-term changes in circulating microparticles levels in patients with kidney transplantation were previously reported in a smaller patient population (15, 16). …”

“…In kidney transplant recipients, levels of circulating EMP were significantly decreased one year after transplantation, as compared to pretransplant values in the same patients. Interestingly, patients on cyclosporine and azathioprine immunosuppressive regimen had lower EMP levels post-transplant, as compared to patients who were on tacrolimus and mycophenolate immunosuppressive treatment (16). …”

Protective Effect of Mycophenolate Mofetil on Endothelial Function in an Aortic Allograft Model

“…Additional experiments are required to determine whether the plasma values of these biomarkers may have been higher in the absence of MMF. In addition, these discrepancies could be related to the direct assessment of vascular function in our study when compared with indirect quantification of biomarkers (14). Finally, we observed that the vascular function in the transplanted aorta, which is abrogated in control rats (39), was improved by CsA and MMF and, to a greater extent, by the combination of CsA and MMF.…”

“…Indeed, CsA inhibits the enterohepatic recirculation of MMF and, thus, promotes its elimination (38). Previous data obtained in humans did not suggest these beneficial vascular effects because circulating levels of endothelial cells and vascular cell adhesion molecule-1 were found to be high in transplanted patients treated with tacrolimus, an other CNI, associated with MMF (14). Additional experiments are required to determine whether the plasma values of these biomarkers may have been higher in the absence of MMF.…”

Microparticles in kidney diseases: focus on kidney transplantation

“…They reported the beneficial impact of renal transplantation on endothelial injury through circulating levels of endothelial markers and concluded that these effects are more pronounced in patients treated by CsA/Aza and are impaired in relation with cytomegalovirus (CMV) and cardiovascular diseases. These results are suggestive of the noninvasive endothelial evaluation as an early index of vascular injury [66].…”