Başkent Üniversitesi Makaleler
Permanent URI for this collectionhttps://hdl.handle.net/11727/13096
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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 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.