Khan Asif, El-Charabaty Elie, El-Sayegh Suzanne
Department of Medicine, Staten Island University Hospital, 475 Seaview Ave., Staten Island, NY 10305, USA.
Department of Nephrology, Staten Island University Hospital, 475 Seaview Ave., Staten Island, NY 10305, USA.
J Clin Med Res. 2015 Jun;7(6):371-8. doi: 10.14740/jocmr2104w. Epub 2015 Apr 8.
Organ transplantation has always been considered to be the standard therapeutic interventions in patients with end-stage organ failure. In 2008, more than 29,000 organ transplants were performed in US. Survival rates among transplant recipients have greatly improved due to better understanding of transplant biology and more effective immunosuppressive agents. After transplant, the extent of the immune response is influenced by the amount of interleukin 2 (IL-2) being produced by the T-helper cells. Transplant immunosuppressive therapy primarily targets T cell-mediated graft rejection. Calcineurin inhibitor, which includes cyclosporine, pimecrolimus and tacrolimus, impairs calcineurin-induced up-regulation of IL-2 expression, resulting in increased susceptibility to invasive fungal diseases. This immunosuppressive state allows infectious complication, leading to a high mortality rate. Currently, overall mortality due to invasive fungal infections (IFIs) in solid organ transplant recipients ranges between 25% and 80%. The risk of IFI following renal transplant is associated with the dosage of immunosuppressive agents given, environmental factors and post-transplant duration. Most fungal infections occur in the first 6 months after transplant because of the use of numerous immunosuppressors. Candida spp. and Cryptococcus spp. are the yeasts most frequently isolated, while most frequent filamentous fungi (molds) isolated are Aspergillus spp. The symptoms of systemic fungal infections are non-specific and early detection of fungal infections and proper therapy are important in improving survival and reducing mortality. This article will provide an insight on the risk factors and clinical presentation, compare variation in treatment of IFIs in renal transplant patients, and evaluate the role of prophylactic therapy in this group of patients. We also report the course and management of two renal transplant recipients admitted to Staten Island University Hospital, both of whom developed pulmonary complications secondary to Aspergillus infection.
器官移植一直被视为终末期器官衰竭患者的标准治疗干预措施。2008年,美国进行了超过29000例器官移植手术。由于对移植生物学有了更深入的了解以及使用了更有效的免疫抑制剂,移植受者的生存率有了显著提高。移植后,免疫反应的程度受辅助性T细胞产生的白细胞介素2(IL-2)量的影响。移植免疫抑制治疗主要针对T细胞介导的移植物排斥反应。钙调神经磷酸酶抑制剂,包括环孢素、吡美莫司和他克莫司,会损害钙调神经磷酸酶诱导的IL-2表达上调,从而增加侵袭性真菌病的易感性。这种免疫抑制状态会引发感染并发症,导致高死亡率。目前,实体器官移植受者因侵袭性真菌感染(IFI)导致的总体死亡率在25%至80%之间。肾移植后发生IFI的风险与免疫抑制剂的给药剂量、环境因素以及移植后的持续时间有关。由于使用了多种免疫抑制剂,大多数真菌感染发生在移植后的前6个月。白色念珠菌和新型隐球菌是最常分离出的酵母菌,而最常分离出的丝状真菌(霉菌)是曲霉菌。系统性真菌感染的症状不具有特异性,早期发现真菌感染并进行适当治疗对于提高生存率和降低死亡率至关重要。本文将深入探讨危险因素和临床表现,比较肾移植患者IFI治疗方法的差异,并评估预防性治疗在该组患者中的作用。我们还报告了两名入住斯塔滕岛大学医院的肾移植受者的病程及治疗情况,他们均因曲霉菌感染继发肺部并发症。