Department of Pharmacology, Rouen University Hospital & INSERM U644, Institute for Biomedical Research, University of Rouen, Rouen, France.
Transpl Int. 2010 Nov;23(11):1135-43. doi: 10.1111/j.1432-2277.2010.01122.x.
This study attempted to establish whether a calcineurin inhibitor (CNI)-free immunosuppressant regimen based on sirolimus (SRL) is associated with a preservation of conduit arteries endothelial function in kidney recipients or not. Twenty-nine kidney recipients were randomized to receive since transplantation SRL (n=15) or cyclosporin A (CsA, n=14) associated with mycophenolate mofetil (MMF) and steroids (6months) in a parallel prospective study. Systolic, diastolic blood pressures, glomerular filtration rate (GFR) and radial artery flow-mediated dilatation (FMD) induced by postischaemic hyperaemia were assessed in a blind manner at one (M1) and 7months (M7) after transplantation. Endothelium-independent dilatation was assessed by glyceryl trinitrate spray. There was no difference between the groups for all vascular parameters at M1. At M7, systolic blood pressure was lower (SRL: 119±3 vs. CsA: 138±4mmHg, P<0.05) and FMD was higher in SRL compared with CsA (SRL: 13.1±0.9 vs. CsA: 9.9±0.9%, P<0.05) without any difference for hyperaemia, endothelium-independent dilatation and GFR (SRL: 66.7±1.05 vs. CsA: 67.5±1.22ml/min). Our results demonstrate that a CNI-free regimen based on SRL and MMF prevents conduit artery endothelial dysfunction compared with CsA and MMF in kidney recipients suggesting a beneficial arterial wall effect that may also contribute to the decrease in systolic blood pressure.
本研究旨在探讨基于西罗莫司（SRL）的无钙调磷酸酶抑制剂（CNI）免疫抑制方案是否与肾移植受者的外分泌腺动脉内皮功能保存有关。29 例肾移植受者随机分为 SRL 组（n=15）或环孢素 A（CsA，n=14）组，两组均在移植后 6 个月内接受吗替麦考酚酯（MMF）和类固醇治疗。采用盲法在移植后 1 个月（M1）和 7 个月（M7）评估收缩压、舒张压、肾小球滤过率（GFR）和动脉血流介导的扩张（FMD）。用硝酸甘油喷雾评估内皮非依赖性扩张。M1 时两组所有血管参数均无差异。M7 时，SRL 组收缩压低于 CsA 组（SRL：119±3 vs. CsA：138±4mmHg，P<0.05），FMD 高于 CsA 组（SRL：13.1±0.9 vs. CsA：9.9±0.9%，P<0.05），而充血、内皮非依赖性扩张和 GFR 无差异（SRL：66.7±1.05 vs. CsA：67.5±1.22ml/min）。我们的结果表明，与 CsA 和 MMF 相比，基于 SRL 和 MMF 的无 CNI 方案可预防肾移植受者的外分泌腺动脉内皮功能障碍，提示动脉壁有益作用，这也可能有助于降低收缩压。
