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肾移植受者早期移植后糖尿病的临床特征、他克莫司药代动力学及相关基因多态性的发生率和危险因素

Incidence and risk factors of clinical characteristics, tacrolimus pharmacokinetics, and related genomic polymorphisms for posttransplant diabetes mellitus in the early stage of renal transplant recipients.

作者信息

Numakura K, Satoh S, Tsuchiya N, Horikawa Y, Inoue T, Kakinuma H, Togashi H, Matsuura S, Tada H, Suzuki T, Habuchi T

机构信息

Department of Urology, Akita University School of Medicine, Hondo, Akita, Japan.

出版信息

Transplant Proc. 2005 May;37(4):1865-7. doi: 10.1016/j.transproceed.2005.02.086.

Abstract

PURPOSE

Posttransplant diabetes mellitus (PTDM) is an important complication in a tacrolimus (TAC)-based immunosuppressive regimen. The present study investigated the incidence, clinical risk factors, TAC pharmacokinetics (PK), and genomic polymorphisms related to TAC-PK or diabetes mellitus (DM) under the TAC-based immunosuppressive protocol.

PATIENTS AND METHODS

Seventy-one nondiabetic renal allograft recipients transplanted from February 1998 to March 2004 were studied. Patients with over 6.5 mg/dL of hemoglobin A1c on sequential blood samples or requiring insulin or oral antidiabetic agents around 6 months after transplantation were diagnosed as having PTDM.

RESULTS

Six months after transplantation, 10 recipients (14.1%) developed PTDM. The positive risk factors were age (P = .003) and body mass index (P = .035). There were no significant differences in gender distribution, pretransplant dialysis period, dialysis modality, acute rejection rate, total steroid doses, TAC-PK, or its related genomic polymorphisms between the two groups. In the DM-related polymorphisms, the frequency of PTDM was significant higher in patients with the VDR TaqI tt or Tt genotype than in those with the TT genotype (P = .013). After a multivariate analysis, age over 50 years (P = .007, odds ratio 8.92) and the presence of VDR TaqI t allele (P = .043, odds ratio 6.71) were correlated with the development of PTDM.

CONCLUSION

The incidence of PTDM in our series was 14.1%. Age over 50 years was a risk factor. The presence of VDR TaqI t allele might be a risk for PTDM. An association between TAC-PK and development of PTDM was not observed.

摘要

目的

移植后糖尿病(PTDM)是基于他克莫司(TAC)的免疫抑制方案中的一种重要并发症。本研究调查了在基于TAC的免疫抑制方案下,PTDM的发生率、临床危险因素、TAC药代动力学(PK)以及与TAC-PK或糖尿病(DM)相关的基因多态性。

患者与方法

对1998年2月至2004年3月间接受移植的71例非糖尿病肾移植受者进行了研究。连续血样中糖化血红蛋白A1c超过6.5 mg/dL或移植后约6个月需要胰岛素或口服降糖药的患者被诊断为患有PTDM。

结果

移植后6个月,10例受者(14.1%)发生PTDM。阳性危险因素为年龄(P = 0.003)和体重指数(P = 0.035)。两组在性别分布、移植前透析时间、透析方式、急性排斥反应发生率、总类固醇剂量、TAC-PK或其相关基因多态性方面无显著差异。在与DM相关的多态性中,维生素D受体(VDR)TaqI tt或Tt基因型患者的PTDM发生率显著高于TT基因型患者(P = 0.013)。多因素分析后,年龄超过50岁(P = 0.007,比值比8.92)和存在VDR TaqI t等位基因(P = 0.043,比值比6.7)与PTDM的发生相关。

结论

我们系列研究中PTDM的发生率为14.1%。年龄超过50岁是一个危险因素。VDR TaqI t等位基因的存在可能是PTDM的一个危险因素。未观察到TAC-PK与PTDM发生之间的关联。

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