title: Role of cytokine gene polymorphisms in acute and chronic kidney disease following liver transplantation.
abstract: OBJECTIVE
  Development of renal dysfunction, including acute kidney injury (AKI) and chronic kidney disease (CKD), after liver transplantation (LT) remains a critical issue adversely affecting patient survival in both the short and long term. Previous reports have suggested that inflammatory and antiinflammatory cytokines and their functionally relevant gene polymorphisms may play critical roles in the development of AKI and CKD. However, the involvement of these cytokines and their gene polymorphisms in renal deterioration following LT remains unclear.
  
  
  METHODS
  We examined 62 recipients who underwent LT at Nagoya University between 2004 and 2009 and who had survived for at least 1 year. The following gene polymorphisms in recipients were analyzed: tumor necrosis factor-A (TNFA) T-1031C, interleukin-2 (IL2) T-330G, IL10 C-819T, IL13 C-1111T, transforming growth factor-B (TGFB) T29C, and IL4 T-33C.
  
  
  RESULTS
  Thirteen patients (21 %) developed AKI within 4 weeks after LT. Of the investigated gene polymorphisms, the IL4 -33 T/T genotype was significantly associated with higher incidence of AKI compared with the other two genotypes [hazard ratio (HR) = 5.48, 95 % confidence interval (CI) 1.18-25.52, p = 0.03]. On the other hand, 16 patients (26 %) had developed CKD at median follow-up of 9.2 years after LT. We showed the lack of association between investigated gene polymorphisms in recipients and CKD development.
  
  
  CONCLUSIONS
  The IL4 -33 T/T genotype might be a risk factor for AKI in LT, and this might contribute to earlier withdrawal of immunosuppressive agents to minimize renal toxicity. In contrast, none of the investigated cytokine gene polymorphisms were associated with CKD.
authors.affiliation: Department of Transplantation Surgery, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan. kamei@med.nagoya-u.ac.jp.
authors.forename: Hideya
authors.initials: H
authors.lastname: Kamei
authors.affiliation: Department of Transplantation Surgery, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Onishi
authors.affiliation: Department of Transplantation Surgery, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ishigami
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D018793:Interleukin-13 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D012189:Retrospective Studies; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; C578095:IL13 protein, human; C508594:IL2 protein, human; C508598:IL4 protein, human; D018793:Interleukin-13; D007376:Interleukin-2; C439524:TNF protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4
keywords: Acute kidney injury; Chronic kidney disease; Cytokine; Gene polymorphism; Liver transplantation