Tacrolimus (FK506)-Associated Renal Pathology.
Tacrolimus (FK506)-Associated Renal Pathology.
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DOI：
10.1097/00125480-199707000-00032
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发表时间：
1997-07-01
影响因子：
6.7
通讯作者：
Demetris, Anthony Jake
中科院分区：
文献类型：
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作者：
Randhawa, Parmjeet S;Starzl, Thomas E;Demetris, Anthony Jake
他克莫司 (FK506) 现在是实体器官移植后公认的主要免疫抑制剂 (1-13)。与传统药物相比，它具有短期和长期优势：与环孢菌素相比，它较少发生排斥反应、高血压和高胆固醇血症。它还被用于挽救对环孢素和 OKT3 没有反应的急性细胞排斥反应的同种异体移植物 (4–6, 8, 14, 15)。环孢素和他克莫司是结构上不相关的化合物，并与靶细胞中不同的胞质蛋白结合。尽管如此，这两种药物都有密切相关的作用机制，主要与白细胞介素 2 mRNA 转录的阻断相关 (16)。这种作用机制的基本相似性与其毒性特征的重叠相平行：两种药物主要对肾脏、中枢神经系统、胃肠道和胰岛有毒。不良事件的总体发生率取决于剂量和临床经验，但两种药物似乎具有可比性 (7,11,17)。两项多中心试验报告他克莫司具有较高的肾毒性、神经毒性和致糖尿病性 (18, 19)，但这些结论受到了批评 (20)。
Tacrolimus (FK506) is now an accepted primary immunosuppressive agent after solid-organ transplantation (1–13). It has both short-term and long-term advantages over conventional drugs: it is associated with less frequent rejection, hypertension, and hypercholesterolemia compared with cyclosporine. It also has been used to salvage allografts with acute cellular rejection not responding to cyclosporine and OKT3 (4–6, 8, 14, 15).Cyclosporine and tacrolimus are structurally unrelated compounds and bind to different cytosolic proteins in target cells. Nonetheless, both drugs have a closely related mechanism of action that is related primarily to a block in the transcription of interleukin-2 mRNA (16). This basic similarity in the mechanism of action is paralleled by an overlap in their toxicity profile: both drugs are toxic principally to the kidneys, central nervous system, gastrointestinal tract, and islets of Langerhans. The overall incidence of adverse events depends on dosage and clinical experience but appears to be comparable for both agents (7, 11, 17). Two multicenter trials report tacrolimus to have higher nephrotoxicity, neurotoxicity, and diabetogenicity (18, 19), but these conclusions have been criticized (20).