Başkent Üniversitesi Yayınları
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Item Torsion of Extraperitoneally Transplanted Kidney: An Unusual Complication(Başkent Üniversitesi, 2013-04) Ozmen, Mehmet Mahir; Koc, Mahmut; Ziraman, Ipek; Bilgic, IsmailTorsion of the extraperitoneally transplanted kidney is rare complication with no clinical data in the literature. The authors present the case of a 44-year-old man with end-stage renal disease who received a kidney transplant from his father. On postoperative day 4, serum urea and creatinine levels increased and urine output decreased. Renal ultrasonography revealed the renal hilum to be rotated to the lateral pelvic border, causing mild pelvocaliectasis, and Doppler ultrasonography, the patients showed a poststenotic flow pattern. After the patient underwent urgent reoperation, all laboratory values and ultrasonography findings returned to normal. To the authors’ knowledge, this is the first published case report of torsion of the extraperitoneally transplanted kidney. When posttransplant deterioration in renal function occurs, renal torsion should be considered in the differential diagnosis.Item Mycophenolic Acid Pharmacokinetics Early After Kidney Transplant(Başkent Üniversitesi, 2013-04) Honarbakhsh, Nazanin; Gholami, Kheirollah; Mohebbi, Niayesh; Javadi, Mohammad Reza; Lesan-Pezeshki, Mahboob; Rouini, Mohammad Reza; Karimzadeh, ImanObjectives: To determine the mycophenolic acid pharmacokinetic profile early after transplant in Iranian kidney graft recipients. Materials and Methods: A cross-sectional study was performed during 6 months in 31 patients who recently had kidney transplant and received fixed doses of mycophenolate mofetil (2 g/d). The plasma levels of mycophenolic acid were determined by high performance liquid chromatography. Results: The mean first mycophenolic acid peak level was 10 ± 5 mg/L. The mean mycophenolic acid area under the curve was 26 ± 19 mgh/L and apparent clearance was 57 ± 55 L/h. The mycophenolic acid area under the curve values of only 8 patients (26%) were within the therapeutic range (30-60 mgh/L). The first, second, and third mycophenolic acid peak levels correlated significantly with mycophenolic acid area under the curve (P < .05). Mycophenolic acid concentration at 10 hours had the highest correlation with mycophenolic acid area under the curve (r=0.962; P < .05). No statistically significant differences were evident in the mean mycophenolic acid area under the curve between men and women. Conclusions: There was a high degree of variation between different patients in mycophenolic acid pharmacokinetics early after kidney transplant.Item Treatment of Liver Transplant Graft-Versus-Host Disease With Antibodies Against Tumor Necrosis Factor-α(Başkent Üniversitesi, 2013-02) Blank, Gregor; Königsrainer, Alfred; Nadalin, Silvio; Handgretinger, Rupert; Kratt, Thomas; Li, JunAcute graft-versus-host disease is uncommon after liver transplant. We recently treated a 60-year-old man with liver transplant for hepatocellular carcinoma. After the primary liver transplant graft did not function, revision liver transplant resulted in excellent function. Subsequently, the patient developed watery diarrhea, systemic inflammatory response syndrome, a skin rash on his limbs and trunk, and palmar erythema. Skin biopsy suggested viral exanthems consistent with cytomegalovirus. Despite treatment for cytomegalovirus, intestinal symptoms worsened. Analysis of peripheral blood with fluorescence-activated cell sorting showed a high proportion of T lymphocytes, with 5% to 10% T cells specific to the second donor, suggestive of graft-versus-host disease. Within 48 hours after beginning therapy with antibodies against tumor necrosis factor-α (infliximab), the skin rash disappeared and endoscopy showed slight improvement of the mucosal regeneration. However, despite antifungal prophylaxis with caspofungin, the patient developed angioinvasive pulmonary aspergillosis and multiple organ failure, and he died. In conclusion, typical clinical symptoms of graft-versus-host disease after liver transplant may include skin rash and gastrointestinal symptoms, and diagnosis may be confirmed by histologic examination and testing for blood chimerism. A consensus for the treatment of graft-versus-host disease still is lacking, but tumor necrosis factor-α is an encouraging target for therapy to decrease the symptoms of graft-versus-host disease and enable mucosal regeneration.Item Vitamin D Receptor Genotype in Pancreas Allograft: A Pilot Study(Başkent Üniversitesi, 2012-10) Rahsaz, Marjan; Esfandiari, Elaheh; Aghdaie, Mahdokht Hossein; Daraie, Masumeh; Karimi, Mohammad Hossein; Yaghubi, Ramin; Ayatollahi, Maryam; Geramizadeh, Bita; Nikeghbalian, Saman; Azarpira, NegarObjectives: Transplanting of pancreatic grafts is an established treatment for diabetes mellitus. Polymorphisms in genes, coding for proteins involved in an immune response, may influence immunologic and nonimmunologic mechanisms that lead to allograft loss. Vitamin D receptor agonists have been shown to increase long-term allograft survival in humans. Materials and Methods: Twenty-one pancreatic recipients transplanted in the Transplantation center of Shiraz University of Medical Sciences were selected and genotyped for the polymorphism of the vitamin D receptor genes (FokI), and the association of each genotype with acute rejection was evaluated. A control group of 100 unrelated otherwise healthy individuals, from the Iranian Blood Transfusion Organization were enrolled. The individuals were selected from Shiraz (a city located in Southern Iran), and the genotype frequency was compared with control group. Results: The overall prevalence acute rejection was 28% (6/21). In the genotype study, homozygous FF presented in 15 patients (71%), heterozygous Ff presented in 6 patients (29%), and no homozygous ff was identified. In the control group, there were 50% with FF, 48% with Ff, and 2% with the ff genotype identified. The only genotype that was detected in rejection group was FF, while the frequency of FF in the nonrejection group was 60%. Conclusions: This study examined several patients to determine whether the vitamin D receptor (FokI) genotype is involved in acute allograft rejection and requires deeper investigation.Item Aggressive Immunosuppressant Reduction and Long-Term Rejection Risk in Renal Transplant Recipients with Pneumocystis jiroveci Pneumonia(Başkent Üniversitesi, 2012-08) Yang, Chih-Yu; Lin, Chih-Ching; Yang, Wu-Chang; Shih, Chia-JenObjectives: Pneumocystis jiroveci pneumonia is a rare but lethal complication in renal transplant recipients. Dose reduction of immunosuppressive agents in such situations is recommended, but its quantity and safety are unclear. Materials and Methods: From January 2001 to January 2011, twenty of one thousand forty-six renal transplant recipients in a single center developed Pneumocystis jiroveci pneumonia, which was diagnosed by the Giemsa and Gomori methenamine silver stains from a specimen of bronchoalveolar lavage. Results: We found that timing of the first immunosuppressant reduction of the Pneumocystis jiroveci pneumonia survivor (mean, 1.4 days after admission) was significantly earlier than that of the deceased patient (mean, 5.1 days after admission). Logistic regression analysis indicated that for those whose immunosuppressants were reduced more aggressively (either 1 of the immunosuppressants was reduced by more than 50% within 2 days of hospitalization) were significantly more likely to survive (mortality risk, OR, 0.074 [95% CI, 0.01-0.84]; P = .035). In addition, none of the survivors developed acute rejection or allograft necrosis during a mean follow-up of 2 years. Conclusions: Dosage reduction of immunosuppressive agents in renal transplant recipients with Pneumocystis jiroveci pneumonia should be prompt and sufficient. Aggressive immunosuppressant dosage reduction is safe in such circumstance and is associated with minimal risk of in-hospital and long-term acute allograft rejection.Item Comparison of 2 Heterotopic Heart Transplant Techniques in Rats: Cervical and Abdominal Heart(Başkent Üniversitesi, 2011-04) Ma, Yi; Wang, GuodongObjectives: Heterotopic heart transplant in rats has been accepted as the most-commonly used animal model to investigate the mechanisms of transplant immunology. Many ingenious approaches to this model have been reported. We sought to improve this model and compare survival rates and histologic features of acute rejection in cervical and abdominal heart transplants. Materials and Methods: Rats were divided into cervical and abdominal groups. Microsurgical techniques were introduced for vascular anastomoses. In the abdominal heart transplant group, the donor’s thoracic aorta was anastomosed end-to-side to the recipient’s infrarenal abdominal aorta, and the donor’s pulmonary artery was anastomosed to the recipient’s inferior vena cava. In the cervical heart transplant group, the donor’s thoracic aorta was anastomosed to the recipient’s common carotid artery, and the donor’s pulmonary artery was anastomosed to the recipient’s external jugular vein. Survival time of the 2 models was followed and pathology was examined. Histologic features of allogeneic rejection also were compared in the cervical and abdominal heart transplant groups. Results: The mean time to recover the donor’s hearts was 7.4 ± 2.2 minutes in the cervical group and 7.2 ± 1.8 minutes in the abdominal group. In the cervical and abdominal heart transplant models, the mean recipient’s operative time was 23.2 ± 2.6 minutes and 21.6 ± 2.8 minutes. Graft survival was 98% and 100% in the cervical and abdominal heart transplant groups. There was no significant difference in graft survival between the 2 methods. Heart allografts rejected at 5.7 and 6.2 days in the cervical and abdominal transplant groups. There was no difference in the histologic features of acute allogenic rejection in cervical and abdominal heart transplant. Conclusions: Both cervical and abdominal heart transplants can achieve a high rate of success. The histologic features of acute allogeneic rejection in the models are comparable.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.