Donor genomics influence graft events: The effect of donor polymorphisms on acute rejection and chronic allograft nephropathy

Objective: 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. Methods: 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]. Results: Multivariate analysis indicated that the presence of the highproduction 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). Conclusion: 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

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“…However, the data we have obtained are generally in accordance with the published literature on the subject (28)(29)(30) .…”

Section: Discussionsupporting

confidence: 91%

Contrasting roles of donor and recipient TGFB1 and IFNG gene polymorphic variants in chronic kidney transplant rejection

Coelho

Ioschpe

Caldas

et al. 2011

Einstein (São Paulo)

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“…There is an emerging interest in the possibility that genetic or biochemical variation among donors plays a role in kidney transplant outcomes. 27,28 It was recently suggested that postreperfusion kidney biopsy transcriptomes or donor genotype can be used to identify donor kidneys at increased risk for DGF. 28,29 In a recent report, Knowing What Works in Healthcare, the Institute of Medicine highlighted that "variations in how health care providers treat specific conditions reflect uncertainty and disagreement about what the clinical standard should be" and that "spending on ineffective care .…”

Section: Discussionmentioning

confidence: 99%

“Nature versus Nurture” Study of Deceased-Donor Pairs in Kidney Transplantation

Louvar

Snyder³

et al. 2009

Journal of the American Society of Nephrology

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Donor characteristics such as age and cause of death influence the incidence of delayed graft function (DGF) and graft survival; however, the relative influence of donor characteristics ("nature") versus transplant center characteristics ("nurture") on deceased-donor kidney transplant outcomes is unknown. We examined the risks for DGF and allograft failure within 19,461 recipient pairs of the same donor's kidneys using data from the US Renal Data System. For the 11,894 common-donor pairs transplanted at different centers, a recipient was twice as likely to develop DGF when the recipient of the contralateral kidney developed DGF (odds ratio [OR] 2.05; 95% confidence interval [CI] 1.82 to 2.30). Similarly, for 7567 common-donor pairs transplanted at the same center, the OR for DGF was 3.02 (95% CI 2.62 to 3.48). For pairs transplanted at the same center, there was an additional 42% risk for DGF compared with pairs transplanted at different centers. After adjustment for DGF, the within-pair ORs for allograft failure by 1 yr were 1.92 (95% CI 1.33 to 2.77) and 1.77 (95% CI 1.25 to 2.52) for recipients who underwent transplantation at the same center and different centers, respectively. These data suggest that both unmeasured donor characteristics and transplant center characteristics contribute to the risk for DGF and that the former also contribute significantly to allograft failure.

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“…Consistently, the renal graft recipients with CCR5-2459 A/A genotype were found to have reduced risk of acute renal graft rejection 70 . On the other hand, the CCR5-2459*A allele is more prevalent in donor kidney that experienced acute cellular rejection, acute rejection or biopsy/proven chronic allograft nephropathy 138 . Furthermore, CCR5-2459 A/G influences neither the incidence of acute liver rejection nor long-term allograft survival after liver transplantation 39 .…”

Section: Transplantationmentioning

confidence: 99%

Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases

Navratilova¹

2006

BIOMED PAP

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Donor genomics influence graft events: The effect of donor polymorphisms on acute rejection and chronic allograft nephropathy

Abstract: These data suggest that many of the donor polymorphisms studied in this analysis may influence a recipient's immune response to a renal allograft. However, their greatest impact may be demonstrated in long-term outcomes.

Cited by 63 publications

References 36 publications

Contrasting roles of donor and recipient TGFB1 and IFNG gene polymorphic variants in chronic kidney transplant rejection

Contrasting roles of donor and recipient TGFB1 and IFNG gene polymorphic variants in chronic kidney transplant rejection

“Nature versus Nurture” Study of Deceased-Donor Pairs in Kidney Transplantation

Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases

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