Abstract
To assess the long-term impact (minimum of 3 years follow-up) of polymorphisms in cytokine genes in donor:recipient pairs on the results of the transplant. We compared genetic cytokine polymorphisms and the primary factors of risk for the development of chronic rejection in paired groups of renal transplant patients with and without chronic allograft nephropathy [CAN]. Multivariate analysis indicated that the presence of the high-production TT genotype (codon 10) of the transforming growth factor beta-1 (TGFB1) was protective in receptors (p=0.017), contrasting with the increased risk when present in donor samples (p=0.049). On the other hand, in the case of the gamma interferon studied, the greater frequency of the high production allele was protective in the analysis of the donor group (p=0.013), increasing the risk of chronic nephropathy of the allograft when present in the recipients (p=0.036). Our results highlight the importance of TGFB1 genotyping in donors, and indicate that polymorphisms in the gene of this cytokine in donor cells might contribute to the development of chronic allograft nephropathy.
Highlights
In spite of accumulated knowledge, the reasons why some patients, but not others, with similar clinical backgrounds, develop chronic rejection after renal transplantation are still unclear
Donor/recipient HLA (Human Leukocyte Antigen) disparity, the basis of alloreactivity and acute rejection, is a major risk factor; donor age, graft cold ischemia time, the number of acute rejection episodes, hyperlipoproteinemia, hypertension, and CMV infection episodes have been established as factors in the progression of chronic allograft dysfunction (reviewed in detail in [4, 5]
We investigated genetic polymorphisms of some cytokine genes involved in the first steps and in the progression of atherosclerosis, in addition to known effector-phase and regulatory cytokines, aiming to identify susceptibility genes for CAN . [14] Polymorphisms of candidate cytokine genes were compared between groups of donor/recipient pairs with or without CAN, which were matched as best possible for major risk factors for CAN, such as level of HLA disparities, type and age of donor, number of acute rejection episodes, presence of hypertension, and cytomegalovirus (CMV) infection
Summary
In spite of accumulated knowledge, the reasons why some patients, but not others, with similar clinical backgrounds, develop chronic rejection after renal transplantation are still unclear. The inflammatory nature of rejection has led to the query on the Chronic allograft nephropathy (CAN) is identified by a progressive decline in renal function, and presents with typical histological features. These include the hallmarks of inflammatory processes, such as mononuclear cell infiltration, perivascular and interstitial inflammation, fibrosis, hyperplasia of the intima leading to partial or total decrease of the vascular lumen, tubular atrophy, and even glomerulosclerosis and ischemia. Donor/recipient HLA (Human Leukocyte Antigen) disparity, the basis of alloreactivity and acute rejection, is a major risk factor; donor age, graft cold ischemia time, the number of acute rejection episodes, hyperlipoproteinemia, hypertension, and CMV infection episodes have been established as factors in the progression of chronic allograft dysfunction
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