MOLECULAR MECHANISMS OF DELAYED KIDNEY GRAFT FUNCTION

K. K?oda¹, L.A. Doma?ski¹, A. Pawlik², K. Safranow³, J. Ró?a?ski¹, M. My?lak¹, K. Serdy?ska¹, M. Kurzawski², M. Dro?dzik², K. Ciechanowski^1
1Clinical Department Of Nephrology, Transplantology And Internal Medicine, Pomeranian Medical University, Stettin/POLAND, ²Department Of Pharmacology, Pomeranian Medical University, Stettin/POLAND, ³Department Of Biochemistry And Medical Chemistry, Pomeranian Medical University, Stettin/POLAND

Body: Introduction Transplantation is the preffered method of treatment in established kidney failure because of prolonging life of the patients and improving quality of their lives. The occurrence of DGF after kidney transplantation is associated with many immunological and nonimmunological factors. Immunological response following renal transplantation is a result of ischemia and reperfusion injury, which increase ICAM-1 and VCAM-1 endothelial expression. Leukocytes activated because of adhesion, secrete proteolytic enzymes and reactive oxygen species that are destructive to the endothelium of transplanted kidney. Reports suggest that genetic variations in ICAM-1 and VCAM-1 synthesis can predestinate to occurrence of DGF and acute renal rejection after kidney transplantation. Methods
We included 270 caucasian patients (104 women and 166 men) after kidney transplantation aged 21 to 76 in the study. Kidney transplantation was perfomed during the period 2000 to 2006 in Clinical Department of General and Transplantation Surgery of the PMU in Stettin and then patients remained under 3 years observation of the Clinical Department of Nephrology, Transplantology and Internal Medicine of the PMU. We singled out patients with delayed graft function (n=85) and with acute renal rejection (n=70). We collected blood samples from the patients for genetic analysis which was performed in the Departement of Pharmacology of the PMU in Stettin by RT-PCR method. Results Comparison of the distribution of genotypes and alleles of the all studied polymorphisms in patients with DGF and in patients without DGF showed no statistically significant differences. Comparison of the distribution of genotypes and allels of rs5498 ICAM-1 gene polymorphism among patients with acute rejection and without acute rejection showed statistically significant differences (p=0,002). Genotype GG of this polymorphism was correlated with higher risk of acute rejection (p=0,003). Comparison of the distribution of genotypes and alleles of the rs1041163 VCAM-1 gene polymorphism showed no statistically significant differences. Comparison of the distribution of genotypes and alleles of the rs3170794 VCAM-1 gene polymorphism among patients with acute rejection and without acute rejection showed differences on the border of statistical significance (p=0,08). Genotype TC of this polymorphism was correlated with higher risk of acute rejection (p = 0,08). Conclusion ICAM-1 and VCAM-1 gene polymorphisms play a minor role in pathogenesis of DGF. GG genotype of the rs5498 ICAM-1 gene polymorphism is a significant risk factor of developing acute renal rejection and TC genotype of the rs 3170794 VCAM-1 gene polymorphism can be a risk factor of acute rejection in renal transplant recipients.

Disclosure: All authors have declared no conflicts of interest.