Ekberg Jana, Ekberg Henrik, Jespersen Bente, Källen Ragnar, Skov Karin, Olausson Michael, Mjörnstedt Lars, Lindnér Per
Transplant Institute, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Transplantation, Skane University Hospital, Malmoe, Sweden.
Transplant Res. 2014 Jun 13;3:12. doi: 10.1186/2047-1440-3-12. eCollection 2014.
Corticosteroids and calcineurin inhibitors (CNIs) are included in renal transplantation immunosuppressive protocols around the world. Well-known side effects are associated with the use of these drugs, including new onset of diabetes after transplantation (NODAT). Long-term patient survival rates are lower among patients with NODAT. The optimal immunosuppressive protocol would therefore include not using corticosteroids and minimization of CNI use.
METHODS/DESIGN: This is a prospective, multi-centre, controlled, randomized, parallel group, open-label study involving kidney transplant patients. The study compares a steroid-free immunosuppressive protocol (study arm A), which is based on low-dose tacrolimus and mycophenolate mofetil (MMF) maintenance therapy together with antithymocyte globulin (ATG) induction, with the conventional immunosuppressive protocol (study arm B), being based on low-dose tacrolimus, MMF and steroids together with interleukin-2 receptor (IL2-R) induction. The study is designed to include most normal-risk patients. It will exclude patients seen as at a high risk of rejection. The primary objective of the study is to assess the cumulative incidence of NODAT in the two study arms 12 months after transplantation using the American Diabetes Association type 2 diabetes diagnostic criteria. The composite measure of freedom from acute rejection, graft survival and patient survival will be evaluated. Renal function and chronic changes in the transplanted kidney will be assessed.
If this study confirms conceptual expectations, namely decreased incidence of NODAT, the steroid-free study protocol could be used with all patients. The regimen could be especially beneficial for patients at a high risk of diabetes mellitus.
EudraCT 2012-000451-13.
全世界的肾移植免疫抑制方案中都包含皮质类固醇和钙调神经磷酸酶抑制剂（CNIs）。使用这些药物会带来一些众所周知的副作用，包括移植后新发糖尿病（NODAT）。NODAT患者的长期生存率较低。因此，最佳免疫抑制方案应不使用皮质类固醇并尽量减少CNI的使用。
方法/设计：这是一项前瞻性、多中心、对照、随机、平行组、开放标签的研究，涉及肾移植患者。该研究将一种无类固醇免疫抑制方案（研究组A）与传统免疫抑制方案（研究组B）进行比较。研究组A基于低剂量他克莫司和霉酚酸酯（MMF）维持治疗并联合抗胸腺细胞球蛋白（ATG）诱导，研究组B基于低剂量他克莫司、MMF和类固醇并联合白细胞介素-2受体（IL2-R）诱导。该研究旨在纳入大多数正常风险患者。将排除被视为有高排斥风险的患者。该研究的主要目的是使用美国糖尿病协会2型糖尿病诊断标准评估移植后12个月两个研究组中NODAT的累积发病率。将评估急性排斥反应、移植物存活和患者存活的综合指标。将评估肾功能和移植肾的慢性变化。
如果本研究证实了概念预期，即NODAT发病率降低，那么无类固醇研究方案可用于所有患者。该方案对糖尿病高风险患者可能特别有益。
EudraCT 2012-000451-13。
