Vincenti F, Tuncer M, Castagneto M, Klinger M, Friman S, Scheuermann E-H, Wiecek A, Russ G R, Martinek A, Nonnast-Daniel B
Kidney Transplant Service, UCSF, San Francisco, California 94143, USA.
Transplant Proc. 2005 Mar;37(2):1001-4. doi: 10.1016/j.transproceed.2004.12.017.
New-onset diabetes mellitus (NODM) is associated with increased risk of graft failure and death in renal transplant recipients. Some clinical studies have indicated that NODM risk is higher with tacrolimus than cyclosporine, but no comparative trial has used American Diabetic Association (ADA)/World Health Organization (WHO) criteria for diagnosis of diabetes mellitus. The Diabetes Incidence After Renal Transplantation, Neoral C2 Monitoring Versus Tacrolimus (DIRECT) study is a 6-month open-label, multicenter trial comparing the impact of tacrolimus and Neoral (cyclosporine microemulsion) on glucose metabolism in 700 de novo kidney transplant recipients, based on ADA/WHO criteria. Patients are randomized to tacrolimus (C0 monitoring) or Neoral (C2 monitoring), stratified by baseline diabetic status and ethnicity. All patients receive basiliximab, corticosteroids, and mycophenolate mofetil or enteric-coated mycophenolate acid (myfortic). Pooled interim 3-month results from a subset of 115 patients receiving either tacrolimus or Neoral showed that the primary efficacy end-point (biopsy-proven acute rejection [BPAR], graft loss or death) occurred in 11 patients (10%). There were four graft losses and only one death, which occurred after graft loss. Eight patients experienced BPAR (7.3%). Among 99 patients who were nondiabetic at baseline, 14 developed NODM by month 3, 17 developed impaired fasting glucose or impaired glucose tolerance, and another 5 patients received hypoglycemic treatment for at least 14 consecutive days or at the month 3 visit, resulting in a 36% incidence of impaired glucose metabolism. At 3 months, median GFR (Nankivell) was 63.7 mL/min; median serum creatinine was 137 micromol/L. Full complete results are expected in December 2005.
新发糖尿病（NODM）与肾移植受者移植失败和死亡风险增加相关。一些临床研究表明，使用他克莫司时NODM风险高于环孢素，但尚无比较试验采用美国糖尿病协会（ADA）/世界卫生组织（WHO）的糖尿病诊断标准。肾移植后糖尿病发病率、新山地明C2监测与他克莫司（DIRECT）研究是一项为期6个月的开放标签、多中心试验，根据ADA/WHO标准，比较他克莫司和新山地明（环孢素微乳剂）对700例初次肾移植受者糖代谢的影响。患者按基线糖尿病状态和种族分层，随机分为他克莫司组（C0监测）或新山地明组（C2监测）。所有患者均接受巴利昔单抗、皮质类固醇以及霉酚酸酯或肠溶型霉酚酸（米芙）治疗。对接受他克莫司或新山地明治疗的115例患者子集进行的3个月汇总中期结果显示，主要疗效终点（活检证实的急性排斥反应[BPAR]、移植失败或死亡）发生在11例患者中（10%）。有4例移植失败，仅1例死亡，且死亡发生在移植失败后。8例患者发生BPAR（7.3%）。在99例基线时无糖尿病的患者中，14例在第3个月时发生NODM，17例出现空腹血糖受损或糖耐量受损，另有5例患者连续至少14天或在第3个月就诊时接受降糖治疗，导致糖代谢受损发生率为36%。在3个月时，中位肾小球滤过率（南基韦尔）为63.7 mL/分钟；中位血清肌酐为137微摩尔/升。完整结果预计于2005年12月公布。
