Role of cytokine gene polymorphisms in acute and chronic kidney disease following liver transplantation.

Abstract

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. We examined 62 recipients who underwent LT at Nagoya University between 2004 and 2009 and who had survived for at least 1year. 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. Thirteen patients (21%) developed AKI within 4weeks 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 9.2years after LT. We showed the lack of association between investigated gene polymorphisms in recipients and CKD development. 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.