Association of cytokine polymorphisms with subclinical progressive chronic allograft nephropathy in Japanese renal transplant recipients: preliminary study.
BACKGROUND
The present study calculated the risk of developing subclinical progressive chronic/sclerosing allograft nephropathy (CAN) under tacrolimus-based immunosuppression according to genetic polymorphisms of cytokines and growth factors, and clinical events including delayed graft function (DGF), acute rejection (AR) and cytomegalovirus (CMV) infection.


METHODS
The subjects were 50 recipients with stable graft function more than one year after renal transplantation. The criteria for subclinical progressive CAN were CAN grade 2 or 3 changes on Banff classification and stable serum creatinine (SCr) levels. Ten genetic polymorphisms were assessed.


RESULTS
Eleven patients (22.0%) developed progressive CAN. The mean ages and SCr levels of recipients with and without progressive CAN were 41.2 and 47.1 years, and 1.46 and 1.22 mg/dL, respectively. There were no significant differences in donor age, number of HLA mismatches, DGF or CMV infection. Although the rate of AR episode seemed to be greater in patients with subclinical progressive CAN, the difference did not reach significance (P = 0.093). The frequencies of the interleukin (IL)-2 T-330G TT genotype (P = 0.046) and IL-4 C-590T C allele (P = 0.092) were higher in patients with progressive CAN. In univariate analysis, the presence of IL-2 T-330G TT (OR 4.57, P = 0.044) was associated with CAN development.


CONCLUSIONS
The presence of IL-2 T-330G TT genotype may be a risk factor for CAN. Further studies with a large number of subjects and analyses of many cytokine polymorphisms would contribute to the ability to make prognostic determinations or tailor immunomodulatory regimens after renal transplantation.
Satoh
Shigeru
S
Department of Urology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Japan. shigerus@doc.med.akita-u.ac.jp
Saito
Mitsuru
M
Inoue
Kazuyuki
K
Miura
Masatomo
M
Komatsuda
Atsushi
A
Habuchi
Tomonori
T
D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007376:Interleukin-2 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D007564:Japan; D007674:Kidney Diseases / Q000209:etiology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016559:Tacrolimus / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015847:Interleukin-4; D003404:Creatinine; D016559:Tacrolimus