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.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Numakura
K
K
Department of Urology, Akita University School of Medicine, Hondo, Akita, Japan.
Satoh
S
S
Tsuchiya
N
N
Horikawa
Y
Y
Inoue
T
T
Kakinuma
H
H
Togashi
H
H
Matsuura
S
S
Tada
H
H
Suzuki
T
T
Habuchi
T
T
D015992:Body Mass Index; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016559:Tacrolimus