Imamura Teruhiko, Kinugawa Koichiro, Ono Minoru, Kagami Yukie, Endo Miyoko, Minatsuki Shun, Muraoka Hironori, Kato Naoko, Inaba Toshiro, Maki Hisataka, Hatano Masaru, Yao Atsushi, Kyo Shunei, Komuro Issei
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
Int Heart J. 2013;54(4):222-7. doi: 10.1536/ihj.54.222.
The long-term survival of heart transplantation (HTx) recipients has increased significantly in recent years, however, the nephrotoxic adverse effects of calcineurin inhibitors (CNIs) are still a major concern. Recently, an inhibitor of mammalian target of rapamycin, everolimus (EVL), has emerged as an alternative immunosuppressant drug that may allow CNI dosage reduction and thereby spare renal function. Data were collected from 20 HTx recipients who had received EVL (target trough level 3-8 ng/mL) along with a dose reduction of CNIs and/or mycophenolate mophetil (MMF) and had been followed for 1 year. Estimated glomerular filtration rate increased significantly with a reduction in the CNI dosage in a dose-dependent manner (P < 0.001, r = -0.807). Neutrophil count increased significantly (P < 0.05) with a reduction in the dosage of MMF (P = 0.009, r = -0.671). Cytomegalovirus antigenemia remained negative after EVL administration among all candidates without any antiviral agents (P = 0.001). There were no significant increases in the acute rejection rates among recipients with EVL compared to those without EVL (P = 0.132). An immunosuppressant strategy incorporating EVL could reduce the CNI and MMF dosages, which resulted in improvements in renal dysfunction and neutropenia while maintaining low rejection rates among HTx recipients.
近年来,心脏移植(HTx)受者的长期生存率显著提高,然而,钙调神经磷酸酶抑制剂(CNIs)的肾毒性不良反应仍是一个主要问题。最近,一种哺乳动物雷帕霉素靶蛋白抑制剂依维莫司(EVL)已成为一种替代免疫抑制药物,它可能允许减少CNI的剂量,从而保护肾功能。收集了20名接受EVL(目标谷浓度3 - 8 ng/mL)并同时减少CNI和/或霉酚酸酯(MMF)剂量且随访1年的HTx受者的数据。估计肾小球滤过率随着CNI剂量的减少而显著增加,呈剂量依赖性(P < 0.001,r = -0.807)。中性粒细胞计数随着MMF剂量的减少而显著增加(P < 0.05)(P = 0.009,r = -0.671)。在所有未使用任何抗病毒药物的候选者中,EVL给药后巨细胞病毒血症仍为阴性(P = 0.001)。与未使用EVL的受者相比,使用EVL的受者急性排斥率没有显著增加(P = 0.132)。一种包含EVL的免疫抑制策略可以减少CNI和MMF的剂量,这导致肾功能障碍和中性粒细胞减少得到改善,同时在HTx受者中保持低排斥率。