Burroughs Thomas E, Lentine Krista L, Takemoto Steve K, Swindle Jason, Machnicki Gerardo, Hardinger Karen, Brennan Daniel C, Irish William D, Schnitzler Mark A
Center for Outcomes Research, Department of Internal Medicine, Saint Louis University School of Medicine, St Louis, MO 63104, USA.
Clin J Am Soc Nephrol. 2007 May;2(3):517-23. doi: 10.2215/CJN.00620206. Epub 2007 Mar 14.
Risk for new-onset diabetes (NOD) after renal transplantation is higher with tacrolimus (Tac) than with cyclosporine (CsA), but the extent to which the diabetogenic effect of Tac is dosage dependent or steroid dependent remains uncertain. Patients who received a transplant between 1995 and 2002 were drawn from the United Network for Organ Sharing registry and prescription records and NOD diagnoses from Medicare claims, both provided by the United States Renal Data System. Patients were divided into six groups of steroid and Tac doses at 30 d after transplantation and referenced against CsA. Relative hazards of NOD with Cox proportional hazards regression were estimated incorporating propensity scores for Tac and nonimmunosuppressive factors related to NOD. A total of 8839 patients with valid immunosuppression records and without pretransplantation evidence of diabetes were included in the study. Unadjusted, cumulative, NOD incidence 1 yr after transplantation was 14.6% with CsA and 22.2% with Tac and at 3 yr after transplantation was 23.4% with CsA and 32.9% with Tac (P < 0.0001). Neither higher CsA nor higher steroid dosages were associated with NOD in CsA-treated patients. However, NOD hazard was significantly higher with Tac than with CsA in all six steroid/Tac dosing groups, including the cohort with the lowest dosages of Tac (dosage thresholds at 30 d after transplantation <0.12 mg/kg per d [mean 0.07 mg/kg per d] and steroids (<0.75 mg/kg per d; hazard ratio 1.28; 95% confidence interval 1.10 to 1.48; P = 0.0012). Whereas the incidence of NOD is greatest with high Tac dosages, the increased risk versus CsA is sustained with lower Tac dosages. Higher steroid dosages increase the early diabetogenic effect of Tac but not of CsA.
肾移植后，使用他克莫司（Tac）发生新发糖尿病（NOD）的风险高于环孢素（CsA），但Tac的致糖尿病作用在多大程度上依赖于剂量或类固醇仍不确定。1995年至2002年间接受移植的患者来自器官共享联合网络登记处和处方记录，以及美国肾脏数据系统提供的医疗保险索赔中的NOD诊断。患者在移植后30天被分为六组类固醇和Tac剂量组，并与CsA进行对照。采用Cox比例风险回归估计NOD的相对风险，纳入Tac的倾向得分和与NOD相关的非免疫抑制因素。共有8839名具有有效免疫抑制记录且移植前无糖尿病证据的患者纳入研究。未经调整的移植后1年NOD累积发病率，CsA组为14.6%，Tac组为22.2%；移植后3年，CsA组为23.4%，Tac组为32.9%（P<0.0001）。在接受CsA治疗的患者中，较高的CsA剂量或类固醇剂量均与NOD无关。然而，在所有六个类固醇/Tac剂量组中，Tac组的NOD风险显著高于CsA组，包括Tac剂量最低的队列（移植后30天剂量阈值<0.12mg/kg per d[平均0.07mg/kg per d]和类固醇（<0.75mg/kg per d；风险比1.28；95%置信区间1.10至1.48；P=0.0012）。虽然高剂量Tac时NOD发病率最高，但与CsA相比，低剂量Tac时风险仍持续增加。较高的类固醇剂量会增加Tac的早期致糖尿病作用，但不会增加CsA的早期致糖尿病作用。
