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西罗莫司与依维莫司对心脏移植受者血脂谱和血液学参数影响的比较。

Comparison of sirolimus and everolimus in their effects on blood lipid profiles and haematological parameters in heart transplant recipients.

作者信息

Tenderich Gero, Fuchs Uwe, Zittermann Armin, Muckelbauer Rebecca, Berthold Heiner K, Koerfer Reiner

机构信息

Department of Cardio-Thoracic Surgery, Heart Center North-Rhine Westfalia, Ruhr University of Bochum, Bad Oeynhausen, Germany.

出版信息

Clin Transplant. 2007 Jul-Aug;21(4):536-43. doi: 10.1111/j.1399-0012.2007.00686.x.

Abstract

The mTOR (mammalian target of rapamycin) inhibitors sirolimus (SRL) and everolimus (EVL) are potent immunosuppressive agents, which allow reducing the dose of the nephrotoxic calcineurin inhibitors cyclosporin and tacrolimus (TAC) in solid organ transplant recipients. However, there is evidence that mTOR inhibitors may lead to myelosuppression and dyslipidemia/hyperlipidemia. We therefore performed a retrospective analysis in heart transplant recipients with renal insufficiency, who received 3.0 mg/d SRL (SRL group; n = 28) or 1.5 mg/d EVL (EVL group; n = 27) each in combination with a reduced TAC dose for at least one yr. Fewer cardiac rejections, but a similar rate of infections occurred in the EVL group compared with the SRL group indicating that the administered EVL dose resulted in a potent immunosuppression. Serum triglyceride and total cholesterol concentrations rose significantly in the SRL group but not in the EVL group. In the SRL group only, the frequency of statin use increased significantly during follow-up. The EVL group showed a significant rise in HDL cholesterol levels during follow-up. There was a slight transient fall in haemoglobin concentrations in the SRL group but not in the EVL group. Leucocyte counts fell significantly in both study groups. However, no cases of leucopenia and also no cases of thrombopenia occurred. In summary, we could demonstrate that in heart transplant recipients with renal insufficiency the introduction of 1.5 mg/d EVL in combination with a reduced TAC dose is effective in preventing cardiac rejections and has less adverse effects on lipid metabolism than the usually prescribed SRL dose, whereas both therapy regimens are not associated with major haematological side-effects.

摘要

雷帕霉素(rapamycin)的哺乳动物靶点(mTOR)抑制剂西罗莫司(SRL)和依维莫司(EVL)是强效免疫抑制剂,可减少实体器官移植受者中具有肾毒性的钙调神经磷酸酶抑制剂环孢素和他克莫司(TAC)的用量。然而,有证据表明mTOR抑制剂可能导致骨髓抑制和血脂异常/高脂血症。因此,我们对肾功能不全的心脏移植受者进行了一项回顾性分析,这些患者分别接受3.0mg/d的SRL(SRL组;n = 28)或1.5mg/d的EVL(EVL组;n = 27),并联合降低剂量的TAC至少一年。与SRL组相比,EVL组的心脏排斥反应较少,但感染发生率相似,这表明所给予的EVL剂量产生了强效免疫抑制作用。SRL组的血清甘油三酯和总胆固醇浓度显著升高,而EVL组则没有。仅在SRL组中,随访期间他汀类药物的使用频率显著增加。EVL组在随访期间高密度脂蛋白胆固醇水平显著升高。SRL组的血红蛋白浓度有轻微短暂下降,而EVL组没有。两个研究组的白细胞计数均显著下降。然而,没有白细胞减少病例,也没有血小板减少病例。总之,我们可以证明,在肾功能不全的心脏移植受者中,引入1.5mg/d的EVL并联合降低剂量的TAC可有效预防心脏排斥反应,并且与通常规定的SRL剂量相比,对脂质代谢的不良影响较小,而两种治疗方案均未出现严重血液学副作用。

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