Association of Interleukin (IL-18) -607A/C and -137C/G Polymorphisms With Early Graft Function In Renal Transplant Recipients
AACC 2014, Chıcago, United States Of America, 27 - 31 July 2014, pp.35, (Full Text)
- Publication Type: Conference Paper / Full Text
- City: Chıcago
- Country: United States Of America
- Page Numbers: pp.35
- Akdeniz University Affiliated: Yes
Abstract
Background:
Recent studies have suggested that increased levels of IL-18 in serum
and renal parenchyma may predict acute rejection in patients with renal transplantation.
IL-18 mediates a wide range of in
fl ammatory and oxidative responses including renal
injury,
fi brosis and graft rejection. It has been reported that the promoter -607 and
-137 polymorphisms of IL-18 in
fl uence the level of cytokine IL-18 expression. This
prospective observational study aimed to assess the relevance of serial postoperative
serum/urine creatinine, cystatin C and IL-18 measurements for monitoring early graft
function in renal transplant recipients and to evaluate the pro-in
fl ammatory property
of IL-18 by measurement of serum IFN-
γ and CRP. We also determined the effect of
IL-18 -607 A/C and IL-18-137 C/G polymorphisms on graft function.
Methods:
This study included 75 renal transplant recipients (28 female, 47 male;
mean age: 38.28 ± 13.03) from living related donors. Blood and urine samples were
collected immediately before and after transplantation at day 7 and month 1. Serum
IFN-
γ, IL-18, creatinine, cystatin C, CRP and urinary IL-18, cystatin C and creatinine
levels were measured. Polymorphisms of the promoter region of the IL-18 gene, IL18-
607A/C and -137C/G were determined by analysis of “real-time PCR/Melting curve”.
GFR values were estimated by Modi
fi ed Diet in Renal Disease (MDRD), Chronic
Kidney Disease Epidemiology Collaboration (CKD-EPI) and some cystatin-C-based
formulas (Larsson, Rule, Hoek). SPSS 20.0 software was used for statistical analysis.
Results:
Serum creatinine, cystatin C, CRP, IFN- γ, IL-18, urine cystatin C levels
and urinary cystatin C/creatinine, urinary IL-18/creatinine ratios were signi
fi cantly
decreased after transplantation (p<0.005). Serum cystatin C and IL-18 levels were
signi
fi cantly higher in patients with IL-18-137 GG genotype before transplantation.
While pretransplant levels of serum creatinine and IL-18 were found signi
fi cantly
higher in patients with IL-18-607 CC genotype, we also observed signi
fi cantly
higher serum IFN-
γ levels and estimated GFR (MDRD and CKD-EPI) values in CA
genotype (p=0.012). Receiver operating characteristic (ROC) analysis was performed
to quantitate the accuracy of the different markers to detect changes in GFR.
Posttransplant serum creatinine and cystatin C demonstrated a signi
fi cantly greater
AUC (area under the curve), sensitivity and speci
fi city values than IL-18 and IFN- γ.
Conclusion:
In this study, although we observed signifi cantly differences in serum
IL-18 levels and some GFR markers according to genotypes, the in
fl uence of
polymorphisms on early graft function has not been clearly shown. Future larger
studies are needed to con
fi rm the association of cytokine gene polymorphisms with
graft function. Prior to transplantation, screening of genetic predisposition which
may have deleterious effect on graft function could lead to the development of
new treatments for better graft survey and ultimately improve the outcome of renal
transplantation.