Romagnoli J, Citterio F, Nanni G, Favi E, Tondolo V, Spagnoletti G, Salerno M Paola, Castagneto M
Department of Surgery, Organ Transplantation, Catholic University, Policlinico Gemelli, Rome, Italy.
Transplant Proc. 2006 May;38(4):1034-6. doi: 10.1016/j.transproceed.2006.03.072.
Sirolimus (SRL) in combination with Cyclosporine A (CsA) and steroids has been shown to lower the incidence of acute renal allograft rejection episodes, allowing CsA sparing. We retrospectively compared the incidence of posttransplant diabetes mellitus (PTDM) among kidney transplant recipients (KTx) immunosuppressed with SRL + CsA versus CsA alone. Patients were divided into two groups: SRL + CsA (n = 38) versus CsA (n = 48). Mean follow-up was 53.9 +/- 17.1 months. Seventeen/86 subjects (19.8%) developed diabetes after transplantation (7 IFG, 8.1%; 10 PTDM, 11.6%). The incidence was significantly higher in SRL + CsA (12/38 patients, 31.6%) compared with CsA (5/43 patients, 10.4%) (P = .0144, odds ratio 3.97). More patients required treatment in the SRL + CsA compared to CsA alone cohort (13.2% vs 2.1%, P = .051): 4 pts (10.5%) became insulin- dependent among SRL+CsA, vs none in the CsA group. Use of OHD was similar in both groups (2.6% SRL + CsA vs 2.1% CsA). There were no significant differences between the two groups in terms of age, sex distribution, BMI, or serum creatinine at 1 to 3 and 5 years from transplantation. All PTDM patients are alive at follow-up, while two grafts were lost due to chronic renal allograft dysfunction. Within the limits of a small retrospective study, we observed that SRL in combination with CsA increased the diabetogenic potential of CsA. A possible explanation of our findings is that higher CsA doses were used in the early experience with SRL + CsA; therefore the higher incidence of PTDM that we observed in the SRL + CsA combination may be a sign of toxicity. Careful monitoring of blood levels is mandatory in the SRL + CsA combination to avoid pleiotropic toxicity.
西罗莫司(SRL)联合环孢素A(CsA)和类固醇已被证明可降低急性肾移植排斥反应的发生率,从而可以减少CsA的用量。我们回顾性比较了接受SRL + CsA免疫抑制的肾移植受者(KTx)与仅接受CsA免疫抑制的肾移植受者中移植后糖尿病(PTDM)的发生率。患者分为两组:SRL + CsA组(n = 38)和CsA组(n = 48)。平均随访时间为53.9±17.1个月。86名受试者中有17名(19.8%)在移植后发生糖尿病(7名空腹血糖受损,8.1%;10名PTDM,11.6%)。与CsA组(43名患者中的5名,10.4%)相比,SRL + CsA组的发生率显著更高(38名患者中的12名,31.6%)(P = 0.0144,优势比3.97)。与仅使用CsA的队列相比,SRL + CsA组中需要治疗的患者更多(13.2%对2.1%,P = 0.051):SRL + CsA组中有4名患者(10.5%)依赖胰岛素,而CsA组中无此情况。两组中口服降糖药的使用情况相似(SRL + CsA组为2.6%,CsA组为2.1%)。在移植后1至3年和5年时,两组在年龄、性别分布、体重指数或血清肌酐方面无显著差异。所有PTDM患者在随访时均存活,而有两个移植物因慢性肾移植功能障碍而丢失。在这项小型回顾性研究的范围内,我们观察到SRL联合CsA增加了CsA的致糖尿病潜力。对我们研究结果的一种可能解释是,在早期使用SRL + CsA时使用了更高剂量的CsA;因此,我们在SRL + CsA联合用药中观察到的较高PTDM发生率可能是毒性的一个迹象。在SRL + CsA联合用药时,必须仔细监测血药浓度以避免多效性毒性。