Başkent Üniversitesi Yayınları
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Item CTLA4 CT60 A/G Gene Polymorphism in Liver Transplant Recipients(Başkent Üniversitesi, 2010-09) Azarpira, Negar; Daraie, Masumeh; Aghdaie, Mahdokht Hosein; Malekhosseini, Seyed AliObjectives: Cytotoxic T-lymphocyte antigen 4 (CTLA4) has a critical role in the down-regulation of the immune response. We retrospectively examined the association between acute rejection and the single nucleotide polymorphism A/G in the CTLA-4 CT60 gene in liver transplant recipients. Materials and Methods: Fifty-one liver transplant recipients with at least 3 months’ follow-up were selected and genotyped for CTLA-4 CT60 polymorphism (HpyCH4 IV). The association of each genotype with allograft acute rejection was evaluated. Results: The mean age of patients was 27.9 ± 15.17 years (minimum, 1 year, maximum, 55 years), with 39% male and 61% female. Overall, 17 recipients (33.3%) experienced acute rejection within the first 3 months after a liver transplant. In our study, 50% of the patients (n=26) have G/A , 31% (n=16) have A/A, and 17% have G/G genotypes (n=9). Distribution of alleles was not different according to underlying liver disease. There also was no difference in sex, age, and distributions of CTLA-4 CT60 alleles with acute rejection episodes. Conclusions: CT60 A/G dimorphism within the 3'-UTR of CTLA4 gene does not influence acute rejection development in liver transplant. However, organ rejection is determined by a combination of several genetic traits rather than a single gene. Therefore, more studies with larger patient numbers are necessary to investigate the effect of combinations of genetic phenotypes involved in this process.Item Liver Transplant: A Primer(Başkent Üniversitesi, 2010-06) Movahedi, Zohreh; Saab, Sammy; Holt, Curtis D.Liver transplant has been accepted as a successful therapeutic option for patients with end-stage liver disease. Patient and graft survival has incrementally increased over the past 2 decades, mainly because of immunosuppressive regimens. However, the nonspecific nature of immunosuppressive agents is associated with an increased risk of development of opportunistic infections, renal impairment, metabolic derangements, neurotoxicity, de novo malignancies, and recurrence of the primary disease. Immunosuppressive regimen pharmacologic classes include calcineurin inhibitors, anti-metabolites, mTOR inhibitors, steroids, and antibody-based therapies. These agents affect T-cell–dependent B-cell activation, and target different sites in the T-cell activation cascade by inhibiting T-cell activation or causing T-cell depletion. The goals of immunosuppression in solid-organ transplant are to prevent allograft rejection as well as optimize allograft function, prolong patient survival, and improve patient quality of life. Therefore, it is essential to carefully select the immunosuppressive regimen that will result in significant improvements in long-term liver transplant patients’ survival and quality of life.Item Value of Donor-specific Antibody Detection in First-Graft Renal Transplant Recipients with a Negative Complement-dependent Cytotoxic Crossmatch(Başkent Üniversitesi, 2009-06) Kamal, Mohamed Mohamed; Ghoneim, Mohamed Ahmed; Mahmoud, Khaled Mohamed; Ismail, Amani Mostafa; Sheashaa, Hussein Attia; Gheith, Osama AshryObjectives: The clinical significance of pretransplant donor specific antihuman leukocyte antigen antibodies that occur despite negative cytotoxicity crossmatches is still unclear. In this study, we assessed the impact of those antibodies on the outcome of renal transplants. Materials and Methods: Our study subjects consisted of 153 living-donor kidney transplant recipients whose pretransplant sera were available. All subjects had a negative complement-dependent cytotoxic crossmatch and were retrospectively evaluated for antihuman leukocyte antigen antibodies and their donor specificities by means of LABScan 100 Flow analyzer (Luminex Corporation, Texas, USA). The follow-up data of all subjects were reviewed. Results: Antihuman leukocyte antigen antibodies were detected in 49 patients, donor nonspecific antihuman leukocyte antigen antibodies were found in 33, and donor specific antihuman leukocyte antigen antibodies were identified in 16. There was a trend toward more acute rejection in the patients with antihuman leukocyte antigen antibodies (22%) than in those without antihuman leukocyte antigen antibodies (17%), but that difference had no statistical significance (P = .378). Patients with donor specific antihuman leukocyte antigen antibodies had a significantly higher incidence of acute cellular rejection (19% vs. 6%, respectively) and vascular rejection (25% vs. 6%, respectively) than did patients with donor nonspecific antihuman leukocyte antigen antibodies (P = .04). Conclusions: Our results suggest that there is a higher incidence of acute rejection in patients with donor specific antihuman leukocyte antigen antibodies and a negative complement-dependent cytotoxic crossmatch; however, those factors had no statistically significant impact on patient or graft survival.Item Acute Tubular Necrosis After Renal Allograft Segmental Infarction: The Nephrotoxicity of Necrotic Material(Başkent Üniversitesi, 2008-12) Ardalan, Mohammad Reza; Shoja, Mohammadali Mohajel; Ghabili, Kamyar; Nasri, HamidObjectives: Renal allograft dysfunction can be caused by renal vessel thrombosis, acute tubular necrosis, hyperacute or acute rejection, nephrotoxicity induced by cyclosporine or tacrolimus, thrombotic microangiopathy, or urinary tract obstruction. Materials and Methods: We describe a renal transplant recipient in whom oliguria developed during the first week after transplant, although his early renal allograft function was good. Results: A Doppler ultrasonographic study revealed a lack of perfusion in the lower pole of the allograft. A perfusion defect was noted in the lower pole that was supplied by a polar artery, which had been damaged during engraftment. Light microscopy disclosed tubular cell necrosis without evidence of vascular or humoral rejection. Conclusions: We suggest that toxic molecules such as tumor necrosis factor-alpha released from a segmental infarcted area can induce tubular cell damage and necrosis leading to renal allograft dysfunction.Item Allograft En Bloc Vagino-Utero-Ovarian Avascular Transplant Versus Autograft Implantation in Rats(Başkent Üniversitesi, 2008-12) Eghtesadi-Araghi, Payam; Moghimi, Mehrdad; Salehian, Mohammad-Taghi; Salehian, Arash; Mossaffa, Nariman; Hadian, MehrnazObjectives: The aim of this study was to compare the results of an allograft en bloc vagino-utero-ovarian avascular transplant with those of autograft implantation in rats. Materials and Methods: Thirty-four inbred adult virgin female Albino rats (age range, 10 - 12 weeks) were divided into 2 groups: the control group (autograft, n=11) and the study group (en bloc vagino-utero-ovariectomy, n=23). In the study group, the uterus and adnexa and the ovaries of the donor rat were transplanted to the recipient animal. Twenty-five to 30 days after that procedure, all rats were killed, and the samples were assessed histopathologically. No immunosuppressive drugs were used. Results: Ten rats died during the postoperative period. In 16 rats, the transplanted system had survived completely at the conclusion of the study. In each of the study groups, complete survival of the uterus and ovaries was noted in 8 rats (34.8% in the study group and 72.8% in the control group). In all rats except 1, histopathologic examination did not reveal any signs of the classic criteria for tissue rejection reaction. The lack of revascularization, nonspecific signs of inflammation, and the presence of large granular lymphocytes and natural killer cells were reported. Conclusions: Our data indicated that the outcome of both allograft and homograft avascular en bloc transplant of vagino-utero-ovariectomy in rats was successful, and that immunologic rejection did not seem to have an important role in those procedures.Item Early Diagnosis and Successful Treatment of Acute Antibody-Mediated Rejection of a Renal Transplant(Başkent Üniversitesi, 2008-09) Yang, Ya-Wen; Tsai, Meng-Kun; Lee, Po-Huang; Wu, Ming-Shiou; Lin, Wei-ChouAntibody-mediated rejection is a delicate situation. It rarely occurs but when it does, it usually results in graft dysfunction and frequently, graft loss. There has been no standard protocol for treating antibody-mediated rejection, although several therapeutic protocols have been recommended. Early detection and treatments of suspected antibody-mediated rejection can secure the graft and improve its function. Here, we describe a typical case of antibody-mediated rejection in a 46-year-old woman who was successfully treated with intravenous immunoglobulin, plasmapheresis, and the anti-CD20 monoclonal antibody, rituximab.Item Association Between Increased Body Mass Index, Calcineurin Inhibitor Use, and Renal Graft Survival(Başkent Üniversitesi, 2008-09) Ghahramani, Nasrollah; Hollenbeak, Christopher; Reeves, W. BrianObjectives: Using data from the US Renal Data System, we examined the relation between body mass index and graft survival as mediated through calcineurin inhibitor use. Materials and Methods: Adult patients who received a first kidney-only transplant, with at least 6 months’ survival were classified into 5 categories (underweight, normal, overweight, obese, and extremely obese) according to body mass index. Associations between calcineurin inhibitor use, body mass index categories, and outcomes were investigated. Results: Underweight and normal-weight recipients lived longer than the other 3 categories, regardless of calcineurin inhibitor use. Graft survival was significantly inferior among obese and extremely obese patients. Average graft survival was significantly higher for recipients with a normal body mass index than it was for overweight, obese, and extremely obese recipients. Risk ratio for graft failure was constant for the calcineurin inhibitor versus the noncalcineurin inhibitor group across all body mass index categories. Mean body mass index for the group with rejection episodes was similar to the group with no rejections; there was no correlation between body mass index and rejection risk. Conclusions: Increased body mass index is associated with inferior patient and graft survival, independent of calcineurin inhibitor use. Because we found no correlation between body mass index and risk of rejection, we assume that, at least after the initial 6 months, the adverse effect of obesity on graft outcome is partially mediated through nonimmunologic mechanisms. When analyzing graft and patient survival rates, we recommend that body mass index be considered a risk factor.Item Influence of Long Chain Polyunsaturated Fatty Acids and Ornithine Concentrations on Complications After Renal Transplant(Başkent Üniversitesi, 2008-06) Alexander, J. Wesley; Woodle, E. Steve; James, J. Howard; Moser, Ann B.; Kuo, Paul C.; Light, Jimmy A.; Succop, Paul; Goodman, Hope R.Objectives: The present study, registered at clinicaltrials.gov with the unique registration number NCT00560014, sought to evaluate the relations between fatty acid concentrations in red blood cells or plasma and amino acid concentrations in plasma on rejection, calcineurin inhibitor toxicity, and new-onset diabetes mellitus. Materials and Methods: Lipid profiles on plasma or red blood cell samples were performed preoperatively and postoperatively in 54 patients. Plasma amino acid profiles were obtained in 49 of these patients. Results: High concentrations of total ω-3 fatty acids, eicosapentaenoic and docosahexaenoic acids in red blood cells, and ornithine in plasma, all were associated with a significantly lower incidence of rejection, whereas high total ω-6 fatty acids were associated with a high rejection rate. Calcineurin inhibitor toxicity was associated with low levels of docosahexaenoic acid, ornithine, and the ω-3 index, and high total ω-6 and ω-3/ω-6 ratios. Inhibition of new-onset diabetes mellitus was seen only with high levels of ornithine. Peak concentrations of fatty acids in red blood cells were not obtained until after 30 days. High levels of arginine were not associated with reduced complications. Conclusions: The levels of selected nutrients in plasma and red blood cell membranes appear to have a profound effect on complications after renal transplant. These preliminary results need confirmation in prospective randomized clinical trials.Item Cytokine Gene Polymorphisms in Renal Transplant Recipients(Başkent Üniversitesi, 2006-12) Azarpira, N.; Aghdaie, MH.; Geramizadeh, B.; Behzadi, S.; Nikeghbalian, S.; Sagheb, F.; Rahsaz, M.; Behzad-Behbahanie, A.; Ayatollahi, M.; Darai, M.; Azarpira, MR.; Banihashemie, M.; Tabei, SZ.Objective: Acute rejection remains an important cause of graft loss after renal transplantation, and cytokines are key mediators in the induction and effector phases of all immune and inflammatory responses. However, the influence of gene polymorphisms on the functional immune response of transplant recipient outcomes remains controversial. Materials and Methods: The amplification refractory mutation system polymerase chain reaction was used to detect the interleukin-10 (IL-10) (-1082 G/A), tumor necrosis factor-alpha (TNF-α) (-308 G/A), and interferon-gamma (IFN-γ) (+874 T/A) single nucleotide polymorphisms in 100 of the first adult kidney recipients at our institution who were receiving cyclosporine-based immunosuppressive therapy. The diagnosis of acute rejection was based on clinical and histologic findings according to the Banff criteria. Results: The results of multivariate analyses showed no significant association between episodes of acute rejection and single nucleotide polymorphisms in IL-10, TNF-α genes, or dinucleotide repeat polymorphisms in the IFN-γ gene. Conclusions: Our results demonstrate that cytokine gene polymorphisms did not influence the early outcome of kidney transplantation.