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

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.