Başkent Üniversitesi Makaleler
Permanent URI for this collectionhttps://hdl.handle.net/11727/13096
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Item Sirolimus Conversion in Liver Transplant Recipients With Calcineurin Inhibitor-Induced Complications: Efficacy and Safety(Başkent Üniversitesi, 2012-04) Ju, Wei-qiang; Hu, An-bin; He, Xiaoshun; Zhu, Xiao-feng; Han, Ming; Tai, Qiang; Wu, Lin-wei; Liang, Wen-hua; Guo, Zhi-yongObjectives: To evaluate the efficacy and safety of conversion from calcineurin inhibitors to sirolimus among liver transplant recipients with calcineurin inhibitor-induced complications. Materials and Methods: After receiving liver transplants, 25 patients with calcineurin inhibitor-induced complications (22 renal dysfunction and 3 new-onset diabetes mellitus) were converted from sirolimus to tacrolimus. The serum creatinine, sirolimus trough level, liver function, acute rejection episodes, and drug-related adverse effects were monitored. Results: The patients were followed for 12 to 50 months (median, 25 months). The renal function of the 22 patients with renal dysfunction improved after sirolimus conversion. The serum creatinine levels were significantly lower at 3 months after conversion versus before conversion (113.2 ± 21.8 µmol/L vs 163.2 ± 45.3 µmol/L; P < .05). At the end of the follow-up, the average serum creatinine level was 101.9 ± 23.4 µmol/L among the 20 living recipients. Diabetes also was under control in 3 diabetic recipients after the conversion. Four patients experienced episodes of acute rejection, and intravenous steroid bolus therapy was administered in 2 of them. No graft was lost because of acute rejection. The adverse effects of sirolimus included hyperlipidemia (7/25), anemia (8/25), and mouth ulcers (9/25). All these adverse effects were relieved after a short-term symptomatic therapy, and no patient was withdrawn from the conversion trial. Conclusions: Sirolimus monotherapy is effective and safe in liver transplant recipients. Conversion to sirolimus was associated with a sustained improvement in renal function and diabetes mellitus without an increased incidence of acute rejection episodes.Item Kaposi Sarcoma of the Ureter After Liver Transplant: Case Report and Literature Review(Başkent Üniversitesi, 2012-02) Chen, Yu; He, Xiao-shun; Qiu, Shao-peng; Zhao, LiangKaposi sarcoma after an organ transplant is rare and infrequently involves internal organs. There are 2 reported cases in the English literature of Kaposi sarcoma originating from the transplant ureter after kidney transplant. We report a case of Kaposi sarcoma that occurred in the native ureter of the liver transplant recipient. Initially, the patient refused any further investigation and management and 2 years subsequent, had to undergo a left radical nephroureterectomy owing to the loss of renal function and distending pain. He recovered very well and no recurrence was detected at 47 months’ follow-up. To our knowledge, it is the first report in English. We review the literature on this topic and explore the therapeutic principles and histologic features of this sarcoma.Item Neurologic Complications After Renal Transplant(Başkent Üniversitesi, 2008-09) Yardimci, Nilgul; Haberal, Mehmet; Zileli, Turgut; Benli, Sibel; Sevmis, Sinasi; Colak, TuranObjectives: Neurologic complications are a significant cause of morbidity and mortality in patients who undergo transplants. We sought to evaluate the nature and incidence of neurologic complications in patients undergoing a renal transplant. Patients and Methods: Between January 2005 and December 2007, 132 adults (35 women, 97 men; mean age, 34.32 ± 0.90 years) underwent a renal transplant at our institution. Associated comorbid medical conditions, presenting neurologic symptoms, and type of immunosuppression were obtained from patients' medical records. Results: Major indications for renal transplant were hypertensive nephropathy (14.4%), vesicoureteral reflux (11.4%), and idiopathic causes (21.2%). Mean follow-up was 17.26 ± 0.89 months (range, 2 weeks to 40 months). Twenty neurologic complications were found in 18 patients (6 women, 12 men; mean age, 33.83 ± 2.37 years). Presenting symptoms included posterior leukoencephalopathy syndrome, 1 (5.6%); cephalgia, 10 (55.6%); cerebral infarcts, 2 (11.1%); seizure, 3 (16.7%); tremor, 2 (11.1%); encephalopathy, 1 (5.6%); and sinus thrombosis, 1 (5.6%). Immunosuppressive agents were the primary cause of 16 of the 20 neurologic complications. Effectiveness and complications of cyclosporine were screened for a total of 1858.50 months, tacrolimus for 853.50 months, and sirolimus for 620 months; 50.2% of the neurologic complications appeared during the first 3 months after transplant; the blood level of immunosuppressive medications did not need to be higher than normal in every case. Discussion: In addition to cyclosporine and tacrolimus, we suggest (for the first time) sirolimus as a cause of neurocomplications after renal transplant.Item A Retrospective Study of Conversion From Tacrolimus-based to Sirolimus-based Immunosuppression in Orthotopic Liver Transplant Recipients(Başkent Üniversitesi, 2008-06) Yu, Si; Huang, Jiefu; Ju, Weiqiang; Zhu,Xiaofeng; Ma, Yi; Yang, Lu; He, XiaoshunObjectives: Calcineurin inhibitors are used widely in liver transplant recipients. Sirolimus is a new, potent immunosuppressant considered to be nonnephrotoxic. There is limited experience with the use of sirolimus in liver transplant recipients. This study aimed to investigate the clinical experience of conversion from tacrolimus-based to sirolimus-based immunosuppression in liver transplant recipients. Patients switched to cyclosporine-based immunosuppression during the same period were enrolled as controls. Materials and Methods: This retrospective study examined liver transplant recipients who had been switched from tacrolimus-based to sirolimus-based or cyclosporine-based immunosuppressive therapy between January 2004 and January 2007 in the first affiliated hospital of Sun Yat-sen University. Patients were divided into 3 groups: those switched to sirolimus-based immunosuppression owing to acute rejection (group SIR-AR; n=11); those switched to sirolimus-based immunosuppression owing to renal insufficiency (group SIR-RI; n=18), and those switched to cyclosporine-based immunosuppression owing to acute rejection (group CsA-AR; n=15) Results: In patients switched owing to acute rejection, the rate of successful conversion was 54.5% in group SIR-AR (6/11) compared with 60% in group CsA-AR (9/15); this difference was not statistically significant (P > .05). After conversion, renal function in patients in group SIR-AR remained normal. Conversely, renal function in patients in group CsA-AR became abnormal 3 months after conversion. In patients who were switched owing to renal insufficiency in group SIR-RI, renal function improved significantly after conversion (P < .05). In the sirolimus groups, some sirolimus-associated adverse effects occurred but were limited and well controlled. Conclusions: Sirolimus can be used safely in liver transplant recipients. In the early stages after liver transplant, sirolimus combination therapy is recommended to prevent acute rejection. For patients with tacrolimus-related adverse effects, a sirolimus-based immunosuppression regimen is a rescue therapy.Item Renal Function and Histology in Kidney Transplant Patients Receiving Tacrolimus and Sirolimus or Mycophenolate Mofetil(Başkent Üniversitesi, 2006-12) Kamar, Nassim; Van, Tuan Tran; Ribes, David; Modesto, Anne; Cointault, Olivier; Lavayssière, Laurence; Ader, Jean Louis; Durand, Dominique; Rostaing, LionelObjective: The aim of this study was to assess the effects of tacrolimus in combination with either sirolimus (n = 10) or mycophenolate mofetil (n = 7) on renal function and renal histopathologic factors 6 and 12 months after kidney transplantation. Materials and Methods: Renal function was assessed by the glomerular filtration rate (as measured by the inulin clearance rate) and by determining renal functional reserve. A renal allograft biopsy was performed at the time of transplantation and 6 and 12 months later. Results: Serum creatinine levels tended to be higher in the sirolimus group 12 months after transplantation. In contrast, inulin clearance and renal functional reserve were similar in both groups 6 and 12 months after transplantation. With respect to histopathologic findings, only mononuclear-cell interstitial inflammation was significantly higher in the sirolimus group than in the mycophenolate mofetil group 12 months after transplantation. However, the progression of tubular atrophy, interstitial fibrosis, and vascular fibrous intimal thickening within the first postoperative year was significantly greater in the sirolimus group. Conclusions: In the long term, the addition of sirolimus to treatment with tacrolimus in de novo renal transplant patients might more adversely affect renal allograft survival than might the addition of mycophenolate mofetil to tacrolimus therapy.Item Mutagenic and Cytotoxic Effects of Immunosuppressive Drugs on Human Lymphocyte Cultures(Başkent Üniversitesi, 2004-12) Oliveira, Vilma Duarte; Zankl, Heinrich; Rath, ThomasObjectives: Immunosuppressive drugs such as cyclosporine A, mycophenolate mofetil, tacrolimus, and the immunosuppressive agent sirolimus are used effectively to prevent immunologic rejection after solid organ transplantation. The most serious complication among patients undergoing immunosuppressive therapy is the risk developing cancer. The question is whether the drugs used have mutagenic properties and so contribute to increased cancer risk. Materials and Methods: We evaluated the mutagenic and cytotoxic effects of the above-mentioned drugs in human lymphocyte cultures with special consideration given to clinically relevant blood-drug concentrations. Mutagenicity was tested by analyzing micronuclei using the well-established cytokinesis-block micronucleus assay with cytochalasin B. To evaluate cytotoxicity, the cytokinesis-block proliferation index was calculated. Concentrations used ranged from 0.1-2 µg/mL for cyclosporine A, 1-20 µg/mL for mycophenolate mofetil, 5-40 ng/mL for tacrolimus, and 2.5-50 ng/mL for sirolimus. We also estimated mutagenicity and cytotoxicity in the blood of kidney transplanted patients using the above-mentioned techniques. Results: Cultures supplemented with mycophenolate mofetil or tacrolimus showed higher amounts of micronuclei when compared with solvent controls in all concentrations tested. Addition of cyclosporine A to cultures also led to a rise in the number of micronuclei at concentrations of 0.2 µg/mL and 0.4 µg/mL. In contrast with the other immunosuppressive drugs, sirolimus induced only weak mutagenic activity in the micronuclei test at its highest concentration (50 ng/mL). Cytotoxic effects were seen only in mycophenolate-mofetil–supplemented cultures at all concentrations tested (P < 0.01). In comparison with healthy persons, those with kidney transplants under immunosuppression displayed a broad reduction in the cytokinesis-block proliferation index (P < 0.001) and a significant increase in the frequency of micronuclei (P < 0.001). Conclusions: Our results indicate that mycophenolate mofetil and tacrolimus display more mutagenic effects in vitro than do cyclosporine A or sirolimus, and that transplanted patients exhibit higher amounts of micronuclei and a noteworthy reduction in the cytokinesis-block proliferation index compared with healthy persons.Item Sirolimus: A Current Perspective(Başkent Üniversitesi, 2003-06) Yakupoğlu, K. Yarkin; D. Kahan, BarrySirolimus, a macrocyclic lactone that displays a novel mechanism of immunosuppressive action, is a critical-dose drug requiring therapeutic drug monitoring for optimal outcomes. The compound was documented in two multicenter, blinded clinical trials to reduce the incidence of acute rejection episodes when used in combination with cyclosporine and steroids vs. azathioprine or placebo comparators. Furthermore, studies utilizing cyclosporine withdrawal documented a long-term benefit on renal function of chronic sirolimus therapy, albeit with a modestly enhanced incidence of acute rejection episodes. Although this application may be useful in selected cases, we believe that minimal initial cyclosporine exposures de novo mitigate the need for eventual withdrawal for chronic nephropathy, while preserving the immunosuppressive synergy during the maintenance phase. Recipients treated de novo with a sirolimuscyclosporine combination tolerate steroid withdrawal at 1 month after living-donor or at 3 to 6 months after cadaveric kidney transplantation with only a 5% risk of acute rejection episodes and 6% incidence of chronic reactions within 3 years. However, sirolimus exacerbates the hypertriglyceridemic and hypercholesterolemic proclivities of transplant recipients, as well as exerts myelosuppressive effects, which are augmented by concomitant therapy with azathioprine or, particularly, with mycophenolate mofetil. Due to its apparent lack of nephrotoxicity, sirolimus has been employed for induction therapy in a calcineurin antag-onist-free regimen in combination with either basiliximab or rabbit antilymphocyte sera for weak or strong immune responders, respectively, followed by introduction of a calcineurin antagonist upon resolution of the ischemia-reperfusion injury. Therefore, sirolimus proffers a potent and unique platform for new immunosuppressive strategies in organ transplantation.