Associação de níveis plasmáticos e polimorfismos em genes de citocinas com a função renal de pacientes transplantados

Abstract

Kidney transplantation is the most desired and cost-effective alternative of renal replacement for end-stage renal disease patients. Cytokines are soluble proteins that influence the immune response. Cytokines polymorphisms can influence their plasma levels and thus affect kidney transplantation. The aim of this study was to investigate the influence of cytokines levels and their polymorphisms on renal graft function and in the presence or not of previous rejection episode. We also evaluated the relationship between these biomarkers and post-transplant time of renal transplant recipients. A total of 146 patients were classified into groups according to creatinine levels (C1: 1,4 and C2: >1,4 mg/dL), estimated glomerular filtration rate (R1: <60 and R2: 60 mL/ min/1.73m2) and presence of previous graft rejection episode (REJ: prior rejection, noREJ: no rejection episode, INDET: indeterminate rejection). The assessment of polymorphisms was performed by PCR-SSP. IL-10 was measured by sandwich ELISA and IL-6 and TNF-á were determined using Multiplex. A higher frequency of the G allele and the GG genotype of -308G>A polymorphism in the TNF-á gene was observed in the R1 group compared to R2. In addition, it was found a higher frequency of the A carrier in the R2 group. The G allele of +25G>C polymorphism in the TGF-â1 gene was more frequent in the REJ group compared to INDET group. TNF-á higher levels were found in the noREJ group compared to INDET group. Furthermore, TNF-á/IL-10 ratio was higher in noREJ group when compared to other groups. The analysis of the time after transplantation showed higher levels of IL-6 in the T1 (time 1 to 24 months post transplantation) and T3 (time 61 to 120 months post transplantation) groups and predominance of IL-10 in T2 group (time 25 to 60 months after transplantation). This study demonstrated a positive correlation between IL-6 and TNF-á and negative correlation between IL-6 and IL-10 as well as IL-6 and post-transplant time. TNF-á also correlated negatively with IL-10. As conclusion, A allele of -308G>A polymorphism in the TNF-á gene is associated with better graft function. Patients who did not present previous rejection episode had higher levels of TNF-á and higher TNF-á/IL-10 ratio. In addition, the +25G>C polymorphism in the TGF-â1 gene was associated with the history of rejection in this study. Genetic influence and balance between cytokine levels may be associated with graft function and patient survival. These biomarkers could be used as potential monitoring tools in renal transplant.