Grinyó Josep M, Cruzado Josep M
Servei de Nefrologia, Hospital Universitari de Bellvitge, University of Barcelona, C. Feixa Llarga s/n, L'Hospitalet, Barcelona, Spain.
Contrib Nephrol. 2005;146:30-42. doi: 10.1159/000082059.
Steroids have accompanied other immunosuppressants throughout the history of renal transplantation. However, its permanent use has been associated with a myriad of adverse effects, which especially increase the already high cardiovascular risk of renal transplant patients. Nevertheless, steroid-sparing strategies may increase the risk of acute and chronic rejection that may worsen the fate of transplant recipients. The advent of new immunosuppressants have renovated the interest on steroid-sparing protocols, and the results of the new trials suggest that these strategies may be safe enough in view of the low rates of acute rejection and stable renal function reported. On the other hand, calcineurin inhibitors (CNIs) have been considered the cornerstone of transplant immunosuppression though their nephrotoxicity has been one of the major clinical problems in the use of these immunosuppressants. The balance between preventing immunological allograft losses and the management of CNI-related nephrotoxicity is still an issue in renal transplantation. CNI reduction or elimination may increase the risk of acute and chronic rejection. Because of these concerns, in most instances CNI have been used at conventional doses in induction and maintenance therapy. As in the case of steroid-sparing strategies, the new therapeutic arsenal has provided a new impulse in CNI-sparing regimens, with an acceptable low rate of acute rejection, well-preserved renal function and without an apparent increased risk of chronic rejection, which may pave the way for a new era in immunosuppression.
在肾移植的历史中,类固醇一直与其他免疫抑制剂一同使用。然而,长期使用类固醇会带来众多不良反应,这尤其增加了肾移植患者本就很高的心血管风险。尽管如此,减少类固醇使用的策略可能会增加急性和慢性排斥反应的风险,从而可能恶化移植受者的预后。新型免疫抑制剂的出现重新激发了人们对减少类固醇使用方案的兴趣,新试验结果表明,鉴于报告的急性排斥反应发生率低且肾功能稳定,这些策略可能足够安全。另一方面,钙调神经磷酸酶抑制剂(CNIs)一直被视为移植免疫抑制的基石,尽管其肾毒性一直是使用这些免疫抑制剂时的主要临床问题之一。在肾移植中,如何平衡预防免疫性移植肾丢失与处理与CNI相关的肾毒性仍是一个问题。减少或停用CNI可能会增加急性和慢性排斥反应的风险。出于这些担忧,在大多数情况下,CNI在诱导和维持治疗中都采用常规剂量使用。与减少类固醇使用的策略一样,新的治疗手段为减少CNI使用的方案带来了新的推动力,急性排斥反应发生率低且可接受,肾功能良好,慢性排斥反应风险没有明显增加,这可能为免疫抑制的新时代铺平道路。