西罗莫司在肝移植中的单一疗法

Sirolimus monotherapy in liver transplantation.

作者信息

Di Benedetto F, Di Sandro S, De Ruvo N, Masetti M, Montalti R, Romano A, Guerrini G P, Ballarin R, De Blasiis M G, Gerunda G E

机构信息

Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia, Modena, Italy.

出版信息

Transplant Proc. 2007 Jul-Aug;39(6):1930-2. doi: 10.1016/j.transproceed.2007.07.018.

DOI:10.1016/j.transproceed.2007.07.018

PMID:17692656

Abstract

INTRODUCTION

Since 1999, a new immunosuppressive drug was administered to renal transplant patients. The SRL molecule acts by blocking post-receptor signal transduction of interleukin-2 (IL-2) interacting with a family of intracellular binding proteins termed immunophilins FKBPs. Among these FKBPs, FK506 12-kd binding protein is the most relevant. SRL is an immunosuppressive drug. Therefore it can inhibit the immune system; at the same time the drug is not nephrotoxic, neurotoxic, and without diabetogenic effects.

METHODS

Among 285 patients who underwent liver transplantation, 27 took Sirolimus as monotherapy. Immunosuppressive treatment upto cyclosporine (CsA) or tacrolimus (FK) associated with steroids (methylprednisolone) and mycophenolate Mofetil (MMF) was initiated among subjects with pre-transplant renal failure. SRL was administered as monotherapy for patients who developed nephrotoxicity, or neurotoxicity, or diabetes. Moreover, patients affected by multifocal HCC who did not meet the Milan criteria or patients who developed Kaposi's Sarcoma were prescribed SRL monotherapy.

RESULTS

Nephrotoxicity occurred in 14 patients with mean serum creatinine level 2.2 mg/dl. Eleven patients with real failure showed significant improvements after a mean period of 28 days of SRL monotherapy (range: 6-45 days). The mean creatinine serum level after treatment with SRL monotherapy was 1.0 mg/dl (range: 0.7-1.2 mg/dl). Neurotoxicity occurred in 4 patients with tremor, confusion, and agitation. Each patient had complete improvement of symptoms after a few days of Sirolimus monotherapy. Among Three patients who developed Kaposi's Sarcoma, two underwent remission. One patient had diabetes due to calcineurin inhibitors, and one showed arterial hypertension not treatable with drugs. After the switch, we treated these patients with medications. Another important indication was HCC not meeting the Milan criteria.

CONCLUSION

SRL monotherapy may be used to manage complication of calcineurin inhibitors or Kaposi's Sarcoma.

摘要

引言

自1999年以来，一种新型免疫抑制药物被应用于肾移植患者。西罗莫司（SRL）分子通过阻断白细胞介素-2（IL-2）的受体后信号转导发挥作用，IL-2与一类称为亲免素FKBP的细胞内结合蛋白家族相互作用。在这些FKBP中，FK506 12-kd结合蛋白最为相关。SRL是一种免疫抑制药物。因此它可以抑制免疫系统；同时该药物无肾毒性、神经毒性，也不会导致糖尿病。

方法

在285例接受肝移植的患者中，27例接受西罗莫司单药治疗。对于移植前有肾功能衰竭的患者，开始采用环孢素（CsA）或他克莫司（FK）联合类固醇（甲泼尼龙）和霉酚酸酯（MMF）进行免疫抑制治疗。对于发生肾毒性、神经毒性或糖尿病的患者，给予SRL单药治疗。此外，对于不符合米兰标准的多灶性肝癌患者或发生卡波西肉瘤的患者，给予SRL单药治疗。

结果

14例患者出现肾毒性，平均血清肌酐水平为2.2mg/dl。11例肾功能衰竭患者在接受平均28天（范围：6 - 45天）的SRL单药治疗后有显著改善。SRL单药治疗后平均血清肌酐水平为1.0mg/dl（范围：0.7 - 1.2mg/dl）。4例患者出现神经毒性，表现为震颤、意识模糊和躁动。每位患者在接受西罗莫司单药治疗几天后症状均完全改善。在3例发生卡波西肉瘤的患者中，2例病情缓解。1例患者因钙调神经磷酸酶抑制剂导致糖尿病，1例患者出现药物无法治疗的动脉高血压。换药后，我们对这些患者进行了药物治疗。另一个重要的适应证是不符合米兰标准的肝癌。