胰肾联合移植后的免疫抑制治疗

背景：胰肾联合移植已经被公认为是糖尿病（包括1型和2型）合并终末期尿毒症的有效治疗手段,由于胰腺为高免疫原性器官,合理的免疫抑制治疗是保证胰腺移植成功的关键。目的：探讨胰肾一期联合移植后免疫抑制药物的合理应用。方法：纳入2005-01/2009-06在中山大学附属第一医院器官移植中心完成胰肾一期联合移植的患者9例,其中男5例,女4例,胰液引流均采用空肠引流方式。术后采用白细胞介素2单克隆抗体诱导的四联免疫抑制方案：白细胞介素2单克隆抗体＋他克莫司＋麦考酚酸＋激素,并逐渐过渡至单用他克莫司维持治疗。回顾性分析以上9例患者围手术期及长期随访情况。结果与结论：胰肾一期联合移植后,除1例早期死亡外,其余8例患者移植后1周内肌酐降至正常水平,移植后停用胰岛素时间为（11.5±3.5）d,空腹血糖恢复至正常时间为（15.4±6.3）d。8例患者随访4～50个月期间,共有4例发生移植肾急性排斥,其中1例在接受床边血液透析过程中并发心脑血管意外后家属放弃治疗,其余3例患者经抗胸腺细胞球蛋白或激素冲击治疗后移植肾功能均逆转恢复,随访过程中未发现移植胰腺排斥。说明胰肾联合移植是治疗糖尿病合并终末期糖尿病肾病的有效方法,术后早期采用白细胞介素2单克隆抗体诱导的四联免疫抑制方案并逐渐过渡至单用他克莫司维持治疗是安全的。

Immunosuppressive regimen after simultaneous pancreas and kidney transplantation

BACKGROUND：Simultaneous pancreas and kidney transplantation （SPK） has been considered an effective therapeutic means of diabetes mellitus （including type 1 and type 2） combined with end stage uremia. Because the pancreas possesses high immunogenicity, so a feasible immunosuppressive regimen is a key to successful pancreas transplantation. OBJECTIVE：To investigate the feasible immunosuppressive regimen after simultaneous pancreas and kidney transplantation （SPK）. METHODS：From January 2005 to June 2009, 9 patients with diabetic nephropathy and end stage uremia, consisting of 5 males and 4 females, received SPK. The pancreatic allograft exocrine secretion was drained into the proximal jejunum via a side-to-side duodenojujunostomy. Quadruple immunosuppressive regimen including induction of interleukin-2 receptor monoclonal antibody, tacrolimus, mycophenolate mofetil and steroid, and gradual tacrolimus monotherapy. The clinical data of the 9 patients were analyzed retrospectively. RESULTS AND CONCLUSION：SPK was successfully applied to all patients without serious surgical complications such as pancreatitis, graft dysfunction and pancreatic fistula. One patient died of cardiovascular accident in the early stage after SPK. The other 8 patients were followed up for 4-50 months. Serum creatinine decreased to normal range within 1 week after surgery. The 8 patients achieved euglycemia during early postoperative stage with insulin independence time （11.5±3.5） days and with fasting blood glucose recovery time （15.4±6.3） days. Acute rejection of the renal graft occurred in 4 patients, 1 patient died of cardiovascular accident and the other 3 recovered after antihuman thymocyte globulin or steroids bolus treatment. No rejection was noted in pancreatic grafts. These findings indicate that SPK is an effective treatment for patients with diabetes mellitus-related middle-and end-stage uremia.Quadruple immunosuppressive regime including interleukin-2 receptor monoclonal antibody induction is feasible after SPK, and such a regimen can be safely converted to tacrolimus monotherapy.