Association of Interleukin (IL-18) -607A/C and -137C/G Polymorphisms With Early Graft Function In Renal Transplant Recipients


AKBAŞ S. H., SÜLEYMANLAR G., GÜLTEKİN M.

AACC 2014, Chıcago, United States Of America, 27 - 31 July 2014, pp.35

  • 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.