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

临床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：强的松龙和甲基强的松龙。在活体亲属和尸体同种异体移植物中，甲基强的松龙比强的松龙在2年移植物存活率方面的临床效果要好得多。我们的比较研究是随机选择两个治疗组，强的松龙/环孢子啉和甲基强的松龙/环孢子啉。移植后2年观察生存率甲基强的松龙组明显高于强的松龙组。这种差异与慢性肾衰竭患者对强的松龙特异性类固醇的耐受性有关。几乎所有慢性肾衰竭患者对甲基强的松龙敏感，而其中20-30%的患者对强的松龙高度耐药。我们检测了慢性肾衰竭患者外周血淋巴细胞对类固醇的敏感性，以便在体外区分耐药患者和敏感患者。根据我们的临床试验，当患者表现出优越的易感性甲基强的松龙时，获得了更好的同种异体移植存活率。强的松龙耐药的一个可能原因被认为是由于淋巴细胞获得性抵抗，以逃避类固醇诱导的凋亡细胞死亡。然而，耐强的松龙淋巴细胞仍然对甲基强的松龙敏感。因此，不同类固醇的淋巴细胞对凋亡细胞死亡的敏感性不同，导致两种类固醇对肾移植的临床结果不同。

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.