Udomkarnjananun Suwasin, Schagen Maaike R, Hesselink Dennis A
Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand.
Excellence Center for Solid Organ Transplantation, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand.
Asian Biomed (Res Rev News). 2024 Jun 28;18(3):92-108. doi: 10.2478/abm-2024-0015. eCollection 2024 Jun.
Immunosuppressive medications play a pivotal role in kidney transplantation, and the calcineurin inhibitors (CNIs), including cyclosporine A (CsA) and tacrolimus (TAC), are considered as the backbone of maintenance immunosuppressive regimens. Since the introduction of CNIs in kidney transplantation, the incidence of acute rejection has decreased, and allograft survival has improved significantly. However, CNI nephrotoxicity has been a major concern, believed to heavily impact long-term allograft survival and function. To address this concern, several CNI-sparing regimens were developed and studied in randomized, controlled, clinical trials, aiming to reduce CNI exposure and preserve long-term allograft function. However, more recent information has revealed that CNI nephrotoxicity is not the primary cause of late allograft failure, and its histopathology is neither specific nor pathognomonic. In this review, we discuss the historical development of maintenance immunosuppressive regimens in kidney transplantation, covering the early era of transplantation, the CNI-sparing era, and the current era where the alloimmune response, rather than CNI nephrotoxicity, appears to be the major contributor to late allograft failure. Our goal is to provide a chronological overview of the development of maintenance immunosuppressive regimens and summarize the most recent information for clinicians caring for kidney transplant recipients (KTRs).
免疫抑制药物在肾移植中起着关键作用，包括环孢素A（CsA）和他克莫司（TAC）在内的钙调神经磷酸酶抑制剂（CNIs）被视为维持免疫抑制方案的核心。自CNIs应用于肾移植以来，急性排斥反应的发生率有所下降，同种异体移植物的存活率也显著提高。然而，CNI肾毒性一直是一个主要问题，被认为对同种异体移植物的长期存活和功能有严重影响。为了解决这一问题，人们开发了几种无CNI方案，并在随机对照临床试验中进行了研究，旨在减少CNI暴露并维持同种异体移植物的长期功能。然而，最近的信息表明，CNI肾毒性并非同种异体移植物晚期失功的主要原因，其组织病理学既不具有特异性也不具有诊断性。在本综述中，我们讨论了肾移植中维持免疫抑制方案的历史发展，涵盖移植早期、无CNI时代以及当前时代，在当前时代，同种免疫反应而非CNI肾毒性似乎是同种异体移植物晚期失功的主要原因。我们的目标是按时间顺序概述维持免疫抑制方案的发展，并为照顾肾移植受者（KTRs）的临床医生总结最新信息。
