Djamali Arjang, Premasathian Nalinee, Pirsch John D
Department of Medicine and Surgery, University of Wisconsin Medical School, Madison, WI 53792, USA.
Semin Nephrol. 2003 May;23(3):306-16. doi: 10.1016/s0270-9295(03)00066-4.
It is estimated that there are greater than 100000 kidney transplant recipients with a functioning graft in the United States. Recent advances in immunosuppression have improved short-term graft survival rates and decreased early mortality by decreasing the incidence and therapy for acute rejection episodes. For those accepted on the waiting list, transplant prolongs patient survival compared with remaining on dialysis. During the 1990s, 3 new immunosuppressive drugs were introduced in clinical kidney transplantation. All were approved for use by the Food and Drug Administration after large, controlled, randomized trials. Mycophenolate mofetil (MMF), when combined with cyclosporine (CSA) and prednisone, lowered acute rejection rates by nearly 50% compared with control. Tacrolimus compared with CSA also significantly reduced acute rejection rates in kidney transplant recipients, but was associated with a significant increase in posttransplant diabetes mellitus (PTDM) in the early trials. When evaluated in combination with MMF, the incidence of PTDM was much lower. At the end of the decade, sirolimus was shown in several randomized trials to lower acute rejection rates and is believed to be less nephrotoxic compared with calcineurin inhibitors. All of the randomized trials were not statistically powered to assess long-term superiority. Registry analyses have been performed that appear to show some long-term benefit of immunosuppressive therapy with MMF. Other outcome assessments in kidney transplant recipients include risk factors for chronic allograft nephropathy, hypertension, hyperlipidemia, and bone disease. Although there are few randomized trials, understanding of the significance of these common complications has progressed and strategies for therapy and intervention have been developed. This article focuses on the randomized trials of immunosuppressive therapy and complications associated with use of these drugs. In addition, we review the current management and intervention for the comorbidities associated with the long-term clinical management of the kidney transplant recipient.
据估计，美国有超过10万名肾移植受者的移植肾仍在发挥功能。免疫抑制方面的最新进展提高了短期移植肾存活率，并通过降低急性排斥反应的发生率和治疗频率降低了早期死亡率。对于那些被列入等待名单的患者，与继续接受透析相比，肾移植延长了患者的生存期。在20世纪90年代，有3种新的免疫抑制药物被引入临床肾移植领域。在经过大型、对照、随机试验后，这些药物均被美国食品药品监督管理局批准使用。霉酚酸酯（MMF）与环孢素（CSA）和泼尼松联合使用时，与对照组相比，急性排斥反应率降低了近50%。他克莫司与CSA相比，也显著降低了肾移植受者的急性排斥反应率，但在早期试验中与移植后糖尿病（PTDM）的显著增加有关。当与MMF联合评估时，PTDM的发生率要低得多。在这十年末，西罗莫司在多项随机试验中显示出可降低急性排斥反应率，并且据信与钙调神经磷酸酶抑制剂相比，其肾毒性较小。所有这些随机试验都没有足够的统计学效力来评估长期优势。已经进行的登记分析似乎显示了MMF免疫抑制治疗的一些长期益处。肾移植受者的其他结局评估包括慢性移植肾肾病、高血压、高脂血症和骨病的危险因素。虽然随机试验很少，但对这些常见并发症的重要性的认识已经取得进展，并且已经制定了治疗和干预策略。本文重点关注免疫抑制治疗的随机试验以及与这些药物使用相关的并发症。此外，我们还综述了肾移植受者长期临床管理中相关合并症的当前管理和干预措施。
