الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Despite continued improvements in immunosuppressive drugs and medical care, the 10-year allograft survival rate of renal transplantation remains disappointingly low, mainly because of chronic allograft nephropathy. Long-term renal allograft survival after kidney transplantation is affected by different variables including donor age, relation to the recipient, kidney preservation methods, recurrent rejection.
Complement (C3) is central to all three complement activation pathways. Activation of the complement cascade is inevitable in kidney transplantation, because of both the specific and nonspecific immunologic responses of the recipient. Local renal complement activation by the donor kidney plays an important role in the pathogenesis of renal injury inherent to kidney transplantation. Local production of C3 in the donor kidney is up-regulated in tubules, and the C3 is deposited on the tubule surface adjacent to the T-cell infiltrate in kidneys during allograft rejection.
A single base substitution in C3 defines two allelic variants: S (slow) and F (fast), based on the differential mobility on gel electrophoresis of the resulting proteins in serum. The allelic frequency of C3F varies markedly among races: 20% among whites, 5% among blacks, and 1% among Asians. Generally, the presence of the F allele has a detrimental effect. In disease-association studies, an increased prevalence of the C3F allotype has been linked to a number of immune-mediated diseases, such as IgA nephropathy, systemic vasculitis, mesangiocapillary glomerulonephritis, and age-related macular degeneration.
Analysis of C3 polymorphisms in both the donor and recipient is an elegant, noninvasive, method to study the relevance of complement in human kidney transplantation. Also typing both donor and recipient for these polymorphisms, allows us to identify patients at increased risk for acute or chronic graft dysfunction. This information may allow us to predict outcome more accurately and thus identify high risk patients who require more intensive surveillance or different immunosuppressive regimens.
Our study was initiated to provide insights on the influence of the donor C3 allotype on renal transplant outcome, taking all different donor types into account. The present study was conducted on 50 pairs of donors and recipients of renal transplantation who fulfill the inclusion and exclusion criteria. C3 allotypes of donor–recipient pairs were determined and divided into four genotypic groups according to the C3F allotype of the donor and the recipient, (SS recipient and FS or FF donor, SS recipient and donor, FS or FF recipient and SS donor, and FS or FF recipient and donor). The four genotypic groups were analyzed for association with graft function, assessed by serum Creatinine, blood urea and GFR.
In the present study we found that, the presence of the C3F allele in the donor kidney is beneficial in transplant recipients who do not themselves possess the C3F allele. These results regarding the protective effect of the donor C3F allele on renal allograft survival of donor kidneys shows that graft survival was significantly prolonged, no graft losses were attributed to chronic allograft nephropathy, and renal function (as indicated by the glomerular filtration rate, serum Creatinine, blood urea) was improved.
This indicates that the presence of C3 (F) allele either homozygous or heterozygous in the donor and the absence of this allele in the recipient give a better renal allograft function and graft survival.