Quantitative variables were compared using the 0.15 in the univariate analysis or variables biologically relevant in the populace analysis. (B) In patients without thymoglobulin induction therapy. according to log-rank test. Rbin-1 Image_3.JPEG (88K) GUID:?8B5DBA3C-EDCD-4F8A-BEAE-DF933A73D385 Supplementary Table 1: Demographic and clinic characteristics of the kidney transplant cohort. Table_1.DOCX (29K) GUID:?B84FB90E-777A-45C6-849A-EE2EBC4BBCEB Supplementary Table 2: Univariate analysis for CMV contamination by the thymoglobulin therapy. Table_2.DOCX (16K) GUID:?61740A75-AC2E-4CBB-B69F-8F844EF48C77 Data Availability StatementThe natural data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any competent researcher. Data are available under accession number PRJEB35786. Abstract The +874 A/T polymorphism in the interferon gamma (= 0.95). The benefit of prophylaxis was observed in all groups with thymoglobulin therapy, but it was maximal in the high-risk CMV contamination group with both thymoglobulin induction therapy and thymoglobulin anti-rejection therapy (HR = 0.01, 0.001). In conclusion, the +874 polymorphism is not a predictive marker of CMV contamination. The protective effect of imTOR is not improved with prophylaxis. Interestingly, the thymoglobulin therapy associated with prophylaxis is not a risk factor for CMV contamination, and prophylaxis is not effective in recipients with no high-risk CMV status and without thymoglobulin therapy. gene is located in chromosome 12q24.1 and the SNP +874 A/T (rs2430561) in the first intron of the gene within the NFkB binding site has been involved in the control of IFN- levels (T allele is associated with higher production of IFN-) (31, 32). Different genotypes of this SNP have been found associated with increased risk of CMV contamination in both, kidney (33) and lung (34) transplant. However, Vu et al. (33) reported association between the AA genotype with increased risk of CMV contamination in 247 kidney transplants, while Mitsani et al. (34) reported that this TT genotype, which correlates with high levels of cytokine production, was significantly associated with the development of CMV disease in 170 lung transplants. These apparently controversial results aimed us to replicate the presumed association of the aforementioned polymorphism with CMV contamination in a well-powered cohort of 600 kidney recipients. Patients and Methods Study Design We performed a retrospective observational study of a kidney transplant cohort. The clinical and research activities being reported are consistent with the considering ethical principles for human research. The study was approved by the local ethics committee and written informed consent was obtained from all patients. Patients and Clinical Data Between January 2005 and December 2015, a total of 709 adult patients received a deceased donor organ in our center. We excluded non Caucasian patients, recipients with graft loss during the first month, and patients who died in the immediate postoperative period. A total of 600 patients were studied. All diagnoses of rejection were confirmed by biopsy, and acute rejection was categorized according to the Banff classification (35, 36). Delayed graft function (DGF) was defined as a need for dialysis in the first week after transplant (37). Immunosuppression and CMV Prophylaxis The immunosuppressive protocol varied over time according to physician criteria. Patients who received a kidney from a brain dead donor were treated mainly with tacrolimus, mycophenolate mofetil, and methylprednisolone. When the organ was donated after circulatory death, most patients received treatment with tacrolimus, mycophenolate mofetil, and methylprednisolone combined with basiliximab or thymoglobulin. Thymoglobulin induction therapy refers to the immunosuppressive treatment given with the aim of preventing acute rejection and consisted of 5C7 daily initial doses of 1 1.25 mg/kg adjusted according to lymphocyte count. In patients who received thymoglobulin, tacrolimus was introduced between days 4 and 6 after transplant. In our center, prophylaxis is given to all CMV D+/RC patients for 6 months. In all patients treated with thymoglobulin, prophylaxis was maintained for 3 months except in Rabbit polyclonal to COT.This gene was identified by its oncogenic transforming activity in cells.The encoded protein is a member of the serine/threonine protein kinase family.This kinase can activate both the MAP kinase and JNK kinase pathways. DC/RC patients who did not received prophylaxis. Out of.This seems to support the idea that prophylaxis does not offer a benefit in patients with imTOR treatment. Conclusion The previously published predictive role of +874 A/T polymorphism as a biomarker for increased risk of CMV infection was not replicated in a statistically well-powered Spanish cohort of kidney transplant patients. of prophylaxis was observed in all groups with thymoglobulin therapy, but it was maximal in the high-risk CMV contamination group with both thymoglobulin induction therapy and thymoglobulin anti-rejection therapy (HR = 0.01, 0.001). In conclusion, the +874 polymorphism is not a predictive marker of CMV contamination. The protective effect of imTOR is not improved with prophylaxis. Interestingly, the thymoglobulin therapy associated with prophylaxis is not a risk factor for CMV contamination, and prophylaxis is not effective in recipients with Rbin-1 no high-risk CMV status and without thymoglobulin therapy. gene is located in chromosome 12q24.1 and the SNP +874 A/T (rs2430561) in the first intron Rbin-1 of the gene within the NFkB binding site has been involved in the control of IFN- levels (T allele is associated with higher production of IFN-) (31, 32). Different genotypes of this SNP have been found associated with increased risk of CMV contamination in both, kidney (33) and lung (34) transplant. However, Vu et al. (33) reported association between the AA genotype with increased risk of CMV contamination in 247 kidney transplants, while Mitsani et al. (34) reported that this TT genotype, which correlates with high levels of cytokine production, was significantly associated with the development of CMV disease in 170 lung transplants. These apparently controversial results aimed us to replicate the presumed association of the aforementioned polymorphism with CMV contamination in a well-powered cohort of 600 kidney recipients. Patients and Methods Study Design We performed a retrospective observational study of a kidney transplant cohort. The clinical and research activities being reported are consistent with the considering ethical principles for human research. The study was approved by the local ethics committee and written informed consent was obtained from all patients. Patients and Clinical Data Between January 2005 and December 2015, a total of 709 adult patients received a deceased donor organ in our center. We excluded non Caucasian patients, recipients with graft loss during the first month, and patients who died in the immediate postoperative period. A total of 600 patients were studied. All diagnoses of rejection were confirmed by biopsy, and acute rejection was categorized according to the Banff classification (35, 36). Delayed graft function (DGF) was defined as a need for dialysis in the first week after transplant (37). Immunosuppression and CMV Prophylaxis The immunosuppressive protocol varied over time according to physician criteria. Patients who received a kidney from a brain dead donor were treated mainly with tacrolimus, mycophenolate mofetil, and methylprednisolone. When the organ was donated after circulatory death, most patients received treatment with tacrolimus, mycophenolate mofetil, and methylprednisolone combined with basiliximab or Rbin-1 thymoglobulin. Thymoglobulin induction therapy refers to the immunosuppressive treatment given with the aim of preventing acute rejection and consisted of 5C7 daily initial doses of 1 1.25 mg/kg adjusted according to lymphocyte count. In patients who received thymoglobulin, tacrolimus was introduced between days 4 and 6 after transplant. In our center, prophylaxis is given to all CMV D+/RC patients for 6 months. In all patients treated with thymoglobulin, prophylaxis was maintained for 3 months except in DC/RC patients who did not received prophylaxis. Out of 308 patients with thymoglobulin induction therapy, 276 (89.6%) received prophylaxis. Antiviral prophylaxis started within the first 1C2 weeks after transplant. The antiviral agent used was ganciclovir or valganciclovir depending on whether the estimated glomerular filtration rate (eGFR) was lower or higher than 15 mL/min, respectively, adjusting dose for renal function. The standard prophylaxis with valganciclovir was according to the technical sheet (https://www.rochecanada.com/PMs/Valcyte/Valcyte_PM_E.pdf) and adjusted for estimated CrCl: 900 mg/day when CrCl 60 mL/ min; 450 mg/day when CrCl = 40C59 mL/min; 450 mg every 2 days when CrCl = 25C39 mL/min; and 450 mg twice a week when CrCl 25 mL/ min. Cytokine Polymorphism Genotyping Genomic DNA was extracted from EDTA-anticoagulated peripheral whole blood. The SNP +874 A/T (rs2430561) was genotyped by TaqMan chemistry and analyzed in a 7900HT Fast Real-Time PCR System (Applied Biosystems, Foster City, CA, USA). The amplification conditions used were those recommended by the manufacturer. CMV Infection and Disease CMV infection was considered as CMV detected in blood in the absence of symptoms. CMV disease was defined according to consensus.