Association of G-137C Interleukin-18 Promoter Polymorphism With Early Renal Glomerulus Injury in Liver Transplantation Recipients

Abstract

As renal injury after transplantation is associated with increased cardiovascular events, mortality, and hepatic allograft dysfunction, early recognition of renal injury and implementing changes may improve the long-term outcome of transplantation. A common cause of renal failure after allo-liver transplantation is calcineurin inhibitor toxicity. However, several other potential causes may also contribute to renal injury after liver transplantation. Recently, interleukin (IL)-18 has been found to have an early and important role in renal injury after transplantation (1). Two single-nucleotide polymorphisms (A-607 C and G-137C) in the promoter region of the IL-18 gene have been repeatedly found to be associated with the IL-18 promoter transcription activity (2). We investigated whether the A-607C and G-137 C IL-18 promoter polymorphism were associated with early renal injury in liver transplantation recipients. Reliance on serum creatinine typically leads to an overestimation of renal function in patients after transplantation. Microproteinuria as a hallmark of reflecting early changes in the glomeruli and proximal tubular function can be used as an accurate predictor to monitor early changes in renal function. We included 152 liver transplantation patients. The recipients were all in a stable stage with normal serum creatinine. The patient with hepatitis C virus and hepatitis B virus infection and diabetes mellitus after transplantation were excluded. When the urine immunoglobulin elevated, we defined this patient had an early renal glomerulus injury (ERGI) and divided the patients into ERGI group (n=37) and no ERGI group (n=115). When the urine α1-microglobulin elevated, we define this patient had an early renal tubular injury (ERTI) and divided the patients into ERTI group (n=106) and no ERTI group (n=46). There is no difference of drug used in those groups (see Table, Supplemental Digital Content 1, https://links.lww.com/TP/A350). We found significant differences in the genotype frequency (P=0.027) and allele frequency (P=0.034) between the ERGI and no ERGI in G-137C IL-18 promoter polymorphism. The GG genotype was significantly more frequent in ERGI compared with no ERGI (Table 1). The genotype and allele frequencies of the G-607C IL-18 promoter polymorphism were not significantly different between the early renal injury groups (see Table, Supplemental Digital Content 2, https://links.lww.com/TP/A351). We can see the tendency that the ERGI and ERTI recipients had higher IL-18 serum levels. However, there was no significant difference (see Figure, Supplemental Digital Content 3, https://links.lww.com/TP/A352).TABLE 1: Analysis on allele and genotype frequencies (%) of IL-18 polymorphism G–137C in alloliver recipients with or without early renal injuryIn conclusion, our study investigated the influence of the G-137C IL-18 promoter polymorphism on early renal injury after liver transplantation. We found that the polymorphism in the IL-18 promoter at position G-137C is associated with an increased risk of ERGI after liver transplantation. The −137GG homozygote was significantly more frequent in ERGI in liver transplantation. As we know that this is the first time to find the relationship between IL-18 gene polymorphism and early renal injury after liver transplantation. The earlier diagnosis of renal injury could lead to more timely intervention, and potentially, to better patient outcomes. This genotype may be a useful marker of ERGI after liver transplantation. Yi Li1 Bin Yang1 Bei Cai1 Lanlan Wang1 Department of Clinical Immunological Laboratory West China Hospital, Sichuan University Chengdu, Sichuan, People's Republic of China Binwu Ying2 Department of Clinical Molecular Laboratory West China Hospital, Sichuan University Chengdu, Sichuan, People's Republic of China Yunying Shi3 Department of Nephrology West China Hospital, Sichuan University Chengdu, Sichuan, People's Republic of China