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Selection of steroids in accordance with lymphocyte abilities and improvement of clinical outcomes of kidney transplantation.

根据淋巴细胞能力选择类固醇和改善肾移植的临床效果。

基本信息

批准号：
06454614
负责人：
OKA Kitaro
金额：
$ 3.71万
依托单位：
The Tokyo University of Pharmacy and Life Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

项目摘要

Prophylactic effects of clinically available glecocorticoids on acute and chronic kidney allograft rejection differed steroid by steroid. There are two steroids which are used for immuno suppressive maintenance therary for kidney transplantation : prednisolone and methylprednisolone. In both living related and cadaveric allografts, methylprednisolone was much superior to prednisolone when their clinical outcomes were compared by 2-years graft survival rates. Our comparative study was carried out with ramdomely selected two treatment groups of recipients, prednisolone/cyclospoline and methylprednisolone/cyclospoline. Observed survival rates for 2 years following transplantation in methylprednisolone group was significantly higher than that of the prednisolone group. This difference related to the prednisolone-specific steroid resistance in chronic renal foilure patients. Almost all chronic renal failure patients are sensitive to methylprednisolone, whereas 20-30% of them are highly resistant to prednisolone. We tested the steroid susceptibilities of peripheral blood lymphocytes taken from the chronic renal failure patients to make differentiation invitro between resistant and sensitive patients. According to our clinical tests, better allograft survival rate was obtained when methylprednisolone to which the patients showed superior susceptibility was used. A possible cause of prednisolone resistant was considered to be resulted from acquired resistance of lymphocytes to escape apoptotic cell death induced by steroid. However, prednisolone-resitant lymphocytes were still susceptible to methylprednisolone. As a result, lymphocyte susceptibilities to apoptotic cell death differed steroid by steroid so that the two steroids gave different clinical outcomes of kidney transplantation.

临床上可用的糖皮质激素对急性和慢性同种异体肾移植排斥反应的预防作用因类固醇而异。有两种类固醇用于肾移植的免疫抑制维持治疗：泼尼松龙和甲基泼尼松龙。在活体相关移植物和尸体同种异体移植物中，当通过 2 年移植物存活率比较临床结果时，甲基泼尼松龙远远优于泼尼松龙。我们的比较研究是随机选择两个治疗组的接受者：泼尼松龙/环孢素和甲基泼尼松龙/环孢素。甲泼尼龙组移植后观察到的2年生存率明显高于泼尼松龙组。这种差异与慢性肾衰竭患者的泼尼松龙特异性类固醇抵抗有关。几乎所有慢性肾功能衰竭患者都对甲泼尼龙敏感，而其中20-30%的患者对泼尼松龙高度耐药。我们测试了取自慢性肾衰竭患者的外周血淋巴细胞的类固醇敏感性，以在体外区分耐药患者和敏感患者。根据我们的临床试验，使用患者表现出较高敏感性的甲泼尼龙可获得更好的同种异体移植存活率。认为泼尼松龙耐药的可能原因是淋巴细胞逃避类固醇诱导的细胞凋亡的获得性抵抗。然而，泼尼松龙耐药的淋巴细胞仍然对甲基泼尼松龙敏感。因此，淋巴细胞对凋亡细胞死亡的敏感性因类固醇而异，因此两种类固醇给出了不同的肾移植临床结果。