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mTOR抑制剂:它们有助于保护肾功能吗?

mTOR inhibitors: do they help preserve renal function?

作者信息

Moro J, Almenar L, Martínez-Dolz L, Agüero J, Rueda J, Arnau M A, Izquierdo M, Cano O, Sánchez-Lázaro I, Salvador A

机构信息

Cardiac Failure and Transplant Unit, Cardiology Service, Valencia, Spain.

出版信息

Transplant Proc. 2007 Sep;39(7):2135-7. doi: 10.1016/j.transproceed.2007.06.066.

Abstract

BACKGROUND

Renal function deterioration is one of the main problems facing heart transplant recipients. The mammalian target of rapamycin (mTOR) inhibitors, in combination with or replacing calcineurin inhibitors, may help preserve renal function. The aim of this study was to evaluate the progression of renal function after switching the immunosuppressive regimen.

PATIENTS AND METHODS

We studied 23 heart transplant recipients (5.5 +/- 4.5 years since transplantation). An mTOR inhibitor was introduced to replace cyclosporine (everolimus, 65%; sirolimus, 35%). Patient clinical characteristics and renal function were studied after switching. The statistical analysis used Student t test for paired data.

RESULTS

The reason for the transplantation was ischemic cardiopathy (52%), dilated myocardiopathy (39%), or other causes (9%). Mean age at time of transplantation was 52 +/- 9 years. Comorbidities were as follows hypertension (43%), insulin-dependent diabetes (22%), hypercholesterolemia (39%), and ex-smokers (70%). The reason for the switch was increased creatinine (65%), appearance of tumors (26%), or others (8%). Previous creatinine level was 1.89 +/- 0.6 mg/dL with clearance of 61.7 +/- 23 mL/min and at the end of follow-up (mean follow-up, 11 +/- 6 months) creatinine level was 2.0 +/- 1.45 mg/dL with clearance of 68.3 +/- 35 mL/min, namely, no significant difference (P = .49 and P = .57, respectively). In the subgroup of patients who switched treatment due to renal dysfunction, initial creatinine level was 2.38 +/- 0.4 mg/dL with clearance of 42.3 +/- 10 mL/min and at the end of follow-up it was 2.28 +/- 0.2 mg/dL and 43.6 +/- 11 mL/min, respectively (P = .68 for creatinine and clearance).

CONCLUSIONS

The introduction of mTOR inhibitors to the immunosuppressant regimen may be useful to delay renal functional deterioration caused by calcineurin inhibitors.

摘要

背景

肾功能恶化是心脏移植受者面临的主要问题之一。雷帕霉素靶蛋白(mTOR)抑制剂与钙调神经磷酸酶抑制剂联合使用或替代钙调神经磷酸酶抑制剂,可能有助于保护肾功能。本研究的目的是评估免疫抑制方案转换后肾功能的进展情况。

患者与方法

我们研究了23例心脏移植受者(移植后5.5±4.5年)。引入mTOR抑制剂以替代环孢素(依维莫司,65%;西罗莫司,35%)。转换后对患者的临床特征和肾功能进行了研究。统计分析采用配对数据的Student t检验。

结果

移植原因包括缺血性心脏病(52%)、扩张型心肌病(39%)或其他原因(9%)。移植时的平均年龄为52±9岁。合并症如下:高血压(43%)、胰岛素依赖型糖尿病(22%)、高胆固醇血症(39%)和既往吸烟者(70%)。转换的原因是肌酐升高(65%)、出现肿瘤(26%)或其他原因(8%)。既往肌酐水平为1.89±0.6mg/dL,肌酐清除率为61.7±23mL/min,随访结束时(平均随访11±6个月)肌酐水平为2.0±1.45mg/dL,肌酐清除率为68.3±35mL/min,即无显著差异(分别为P = 0.49和P = 0.57)。在因肾功能不全而转换治疗的患者亚组中,初始肌酐水平为2.38±0.4mg/dL,肌酐清除率为42.3±10mL/min,随访结束时分别为2.28±0.2mg/dL和43.6±11mL/min(肌酐和肌酐清除率的P = 0.68)。

结论

在免疫抑制方案中引入mTOR抑制剂可能有助于延缓钙调神经磷酸酶抑制剂引起的肾功能恶化。

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