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不同长期免疫抑制治疗的肾移植受者肾上腺功能比较——泼尼松龙与硫唑嘌呤对比泼尼松龙与环孢素

Comparison of adrenal functions in kidney transplant recipients with different long-term immunosuppressive treatments--prednisolone and azathioprine versus prednisolone and cyclosporine.

作者信息

Oka K, Shimodaira H, Hirano T, Sakurai E, Tamaki T, Kozaki M

机构信息

Division of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.

出版信息

Transplantation. 1993 Sep;56(3):603-9. doi: 10.1097/00007890-199309000-00020.

Abstract

Adverse effects of cyclosporine on the adrenal cortex have been documented in animal experiments, but nothing has been reported in human subjects. Endogenous cortisol in peripheral blood was monitored for three years after transplantation, with 30 kidney recipients on two different immunosuppressive treatments. In the azathioprine group, 16 patients were treated with coadministration of prednisolone at an initial dose of 120 mg/day. In the cyclosporine group, 14 patients were also treated with prednisolone, using an initial dose of 60 mg per day. Short ACTH stimulation tests were performed to reconfirm the results obtained by basal cortisol monitoring. During the first year following transplant, cortisol concentrations in the cyclosporine group were higher, though not significantly so, than those in the azathioprine group, in accordance with cumulative amounts of prednisolone administered. At three years, however, the mean cortisol concentrations in the azathioprine group were 2-3 times higher than those in the cyclosporine group (P < 0.05). All patients in the azathioprine group responded well to ACTH, whereas 4 patients out of 14 in the cyclosporine group showed continuous severe suppression without considerable response to ACTH (P < 0.01). In conclusion, we would like to suggest that adrenocortical toxicity of long-term cyclosporine use may appear one year after transplant, resulting in chronic suppression of the adrenal cortex, and, accordingly, difficulty in further reduction of prednisolone use.

摘要

环孢素对肾上腺皮质的不良反应在动物实验中已有记录,但在人类受试者中尚无相关报道。对30例接受两种不同免疫抑制治疗的肾移植受者移植后三年的外周血内源性皮质醇进行了监测。在硫唑嘌呤组,16例患者联合使用初始剂量为120mg/天的泼尼松龙进行治疗。在环孢素组,14例患者也接受了泼尼松龙治疗,初始剂量为每天60mg。进行了短促肾上腺皮质激素刺激试验以再次确认基础皮质醇监测获得的结果。移植后的第一年,根据泼尼松龙的累积给药量,环孢素组的皮质醇浓度高于硫唑嘌呤组,尽管差异不显著。然而,在三年时,硫唑嘌呤组的平均皮质醇浓度比环孢素组高2至3倍(P < 0.05)。硫唑嘌呤组的所有患者对促肾上腺皮质激素反应良好,而环孢素组的14例患者中有4例表现出持续的严重抑制,对促肾上腺皮质激素无明显反应(P < 0.01)。总之,我们认为长期使用环孢素的肾上腺皮质毒性可能在移植后一年出现,导致肾上腺皮质慢性抑制,因此难以进一步减少泼尼松龙的用量。

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