Başkent Üniversitesi Makaleler
Permanent URI for this collectionhttps://hdl.handle.net/11727/13096
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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 Clinicoepidemiologic Study of Posttransplant Diabetes After Living-Donor Renal Transplant(Başkent Üniversitesi, 2008-03) Elmagd, Mogahid M Abu; Wahab, Ahmad M abd El; AMetwally, Abdel Hameed; Bakr, Mohammed A.Objectives: We sought to evaluate posttransplant diabetes mellitus with regard to its incidence, risk factors for occurrence, complications, impact on graft function, and impact on patient and graft survival rates. Materials and Methods: A total of 1580 patients received living-donor renal allografts at Mansoura University, Egypt, between March 1976 and November 2004. Of these, 286 recipients developed diabetes after transplant (diabetic group). These patients were matched with 316 kidney transplant recipients who did not develop diabetes after transplant (control group). A complete clinical history was obtained and a clinical examination was done. Laboratory analyses including urine analysis, complete blood count, total serum cholesterol, fasting and 2-hour postprandial plasma glucose, Hb A1c, serum creatinine, and creatinine clearance were obtained in all patients. In each patient, presence of hepatitis B and C was determined with polymerase chain reaction, and a graft biopsy was obtained to diagnose renal allograft rejection. Results: The onset of diabetes mellitus among our recipients occurred primarily during the first 6 months after transplant (in 52.4% of the patients). Significant correlations were found between posttransplant diabetes mellitus and the recipients’ age (P = .0001), obesity (P = .001), positive family history of diabetes mellitus (P = .001), hepatitis C virus infection (P = .039), cumulative dose of steroids in the first 3 months (P = .047), and calcineurin inhibitor-based immunosuppressive therapy (P = .001). Moreover, posttransplant diabetes mellitus significantly affected rates of coronary heart disease (P = .001), hypertension (P = .02), and hypercholesterolemia (P = .001). Graft survival was similar in both groups until 15-year follow-up, at which time graft survival began to decrease in patients with diabetes mellitus compared with those without diabetes mellitus (43.5% vs 53.6%, P = .013). Similarly, patient survival was similar until 8-year follow-up, at which time survival rates began to decline in patients with diabetes as compared with patients without diabetes (79.9% vs 86.1%, P = .001); this trend continued to the 15-year follow-up (60.6% vs 77.8%, P = .001). Conclusions: Posttransplant diabetes mellitus is a major problem that endangers patient and graft survival. In our population, the incidence of posttransplant diabetes mellitus was 18.2%. Further studies are recommended to screen for patients with impaired fasting glucose and impaired glucose tolerance for prediction, early detection, and better management of posttransplant diabetes mellitus.Item Successful Pulmonary Thromboendarterectomy for Right Atrial Thrombosis in a Heart Transplant Recipient: A Case Report(Başkent Üniversitesi, 2007-06) Bigdeli, A. K.; Beiras-Fernandez, A.; Kaczmarek, I.; Sadoni, S.; Brenner, P.; Schmoeckel, M.; Nikolaou, K.; Reichart, B.Acute massive or submassive pulmonary embolism is a life-threatening condition with a poor prognosis. It causes sudden hemodynamic deterioration and warrants immediate surgery. We report the case of a 41-year-old male heart transplant recipient who had not been treated prophylactically for thrombosis, who was referred to our center because of exertional dyspnea after immobilization owing to an injury in one of his legs. Transesophageal echocardiography revealed a large, mobile, right atrial mass originating from a pacemaker lead. Furthermore, contrast-enhanced computed tomography scanning of the chest revealed multiple pulmonary emboli resulting in subtotal occlusion of both pulmonary arteries. Although typically reserved for patients with chronic thromboembolic pulmonary hypertension, surgical thromboendarterectomy was successfully performed. Six months after discharge, the patient is well and has a New York Heart Association class 1 rating. This is the first report of a successful pulmonary thromboendarterectomy in a heart transplant recipient.Item Severe Tacrolimus Toxicity in Rabbits(Başkent Üniversitesi, 2007-06) Giessler, Goetz A.; Gades, Naomi M.; Friedrich, Patricia F.; Bishop, Allen T.Objectives: Tacrolimus is an effective immunosuppressant, safely administered in clinical practice by monitoring blood levels. In experimental transplants, many dosage regimens have been reported, often without such determinations. Anorexia and organ toxicity commonly occur. We report the toxic effects of tacrolimus in rabbits receiving intramuscular injections (1 mg/kg/d) and the subsequent dosage modifications that resulted in improved animal survival without toxic effects. Materials and Methods: To obtain nontoxic drug concentrations in the blood, 3 dosage regimens were required. Drug concentrations were targeted using therapeutic human values as a guide (range, 5-20 ng/mL). First, a group of 12 Dutch Belted rabbits received vascularized femoral allografts and were treated with intramuscular dosages of tacrolimus (1 mg/kg/d) for 14 days. Subsequently, dosage reductions in 10 more rabbits, to 0.2 mg/kg/d for 14 days, were necessary. Finally, another group of 20 rabbits was treated with 0.08 mg/kg for 3 days, and then every other day thereafter. Weight loss > 30%, cardiopulmonary failure, and/or creatinine levels > 221 µmol/L were the criteria approved by our local Institutional Animal Care and Use Committee for euthanizing the animals. Treated animals were compared with 20 nonimmunosuppressed controls that underwent the same operation. Results: At an intramuscular dosage of 1 mg/kg/d, the mean tacrolimus blood level was 90.7 ng/mL. Ten of the 12 animals in the original group died or required euthanasia. At necropsy, renal failure, cardiac abnormalities, and pulmonary edema were found. The tacrolimus dosage of 0.2 mg/kg/d produced a mean tacrolimus blood level of 17.6 ng/mL; however, 8 of the subsequent 10 rabbits died when given this dosage. Ultimately, the 0.08 mg/kg regimen in 20 rabbits permitted survival of 18 animals with a mean tacrolimus blood level of 6.8 ng/mL. None of 20 nonimmunosuppressed controls died after surgery. Conclusions: For successful immunosuppression, Dutch-Belted rabbits require intramuscular tacrolimus dosages lower those required in other rabbit breeds. This has not been reported previously. The 0.08 mg/kg/d dosage combined with intermittent drug level monitoring permits survival without significant complications.Item Cytomegalovirus Disease with Atypical Presentation in a Renal Transplant Patient: Case Report(Başkent Üniversitesi, 2006-06) Khosravi, Masoud; Nobakht, Ali; Nikokar, Abdolah R.Infection is a major problem after kidney transplantation. Cytomegalovirus (CMV) is the most common viral infection affecting transplant patients. This report presents a rare clinical manifestation of CMV in the form of a hemorrhoid in a 58-year-old woman. One week after undergoing an external hemorrhoidectomy, the patient presented with fever, leukopenia, and thrombocytopenia. Pathological analysis showed CMV in the hemorrhoidal tissue, which was confirmed via a positive PP65 antigenemia assay. Therapy with ganciclovir (250 mg IV b.i.d. for 2 weeks) was started. The patient’s response to treatment was good, and she has been doing well since that time. Her plasma creatinine level 2 years later was 79.2 µmol/L (normal range, 53-106 µmol/L). Physicians must always be aware of the hazards of CMV in immunocompromised patients with typical, and even with atypical, presentations. Taking into consideration the statement, “prophylaxis precedes treatment,” nephrologists must try to detect CMV in their patients (especially during the first 6 months after transplantation) prior to the appearance of any clinical manifestations. If CMV is detected, pre-emptive therapy with ganciclovir should be started.Item Ischemic Training and Immunosuppressive Agents Reduce the Intensity of Ischemic Reperfusion Injury after Kidney Transplantation(Başkent Üniversitesi, 2006-06) Treska, Vladislav; Molacek, Jiri; Kobr, Jiri; Racek, Jaroslav; Trefil, Ladislav; Hes, OndrejObjectives: Ischemia-reperfusion injury affects posttransplant renal function, directly increases the probability of acute rejection, and is associated with chronic rejection and impaired long-term function. Animal studies suggest that ischemic preconditioning enhances resistance to ischemia and may be augmented by treating donors using immunosuppressant agents. This study sought to confirm the hypothesis that a combination of ischemic training and immunosuppression prior to renal harvest would maximize a transplanted kidney’s resistance to ischemia-reperfusion injury. Materials and Methods: Landrace pigs underwent either preharvest immunosuppression plus left kidney ischemic training (group 1, n = 6) or ischemic training alone (group 2, n = 6). Immunosuppression was composed of mycophenolate mofetil (20 mg/kg) and tacrolimus (0.1 mg/kg) administered intravenously 30 minutes before training. Training comprised 2 cycles of left renal pedicle occlusion for 5 minutes followed by release (reperfusion) for 10 minutes. Warm renal ischemia was then induced by clamping the left renal pedicle for 30 minutes, followed by heterotopic left kidney transplantation. Blood from the transplanted kidney renal vein was sampled directly at 0, 10, 20, 40, and 60 minutes posttransplantation for malondialdehyde (a reactive oxygen species marker), tumor necrosis factor-alpha (TNFα), interleukins 6 and 8 (inflammatory cytokines), and erythrocyte-reduced glutathione (an antioxidant). Renal histology was graded on a 3-point scale. Results: Reperfusion levels of malondialdehyde, TNFα, and interleukin 6 were significantly lower in group 1 at both 40 and 60 minutes. None of the animals in group 1 (0/6) that received preharvest immunosuppression showed severe interstitial inflammation, compared with 4 of 6 animals in group 2 that did (P < .03). Conclusions: Preharvest immunosuppression with mycophenolate mofetil and tacrolimus significantly decreases immediate posttransplant reactive oxygen species and inflammatory cytokine production, enhances the protective effect of ischemic training, and should not only reduce ischemia-reperfusion injury in transplanted kidneys but also should enhance immediate and long-term graft function while preventing acute rejection.Item Immunosuppressive Strategies in Organ Transplantation in the Light of Innate Immunity(Başkent Üniversitesi, 2006-06) Land, Walter GottliebEvidence has accumulated to support the notion that injury-induced activation of the donor’s and the recipient’s innate immune system largely determines the outcome of organ transplantation. Future potential therapeutic strategies to suppress events of both innate immune systems, as well as approaches to mitigate allograft injury, are discussed with regard to inhibiting both complement activation and dendritic cell maturation, and to blocking innate effector functions. Applications of pharmacological drug therapy as well as gene-specific manipulations are theoretical tools to reach these goals. A variety of encouraging experimental data in this research field are already available and promise further discoveries that ultimately will lead to the design of appropriate clinical trials.Item Cyclosporine Lymphocyte Maximum Level Monitoring in De Novo Kidney Transplant Patients: A Prospective Study(Başkent Üniversitesi, 2006-06) Barbari, AG; Masri, MA; Stephan, AG; Ghoul, B El; Rizk, S; Mourad, N; Kamel, GS; Kilani, HE; Karam, ASObjectives: To determine prospectively the temporal variations of cyclosporine-A lymphocyte maximum level, whole blood maximum concentration, and total lymphocyte count in patients with de novo kidney transplantation. Materials and Methods: Lymphocyte maximum level, whole blood maximum concentration, and total lymphocyte count were prospectively measured in 35 patients at 1, 2, and 3 months after kidney transplantation. Two groups—a biopsy-proven acute rejection group (REJ+) and a rejection-free group (REJ-)—were compared. Results: Both groups had similar lymphocyte maximum levels, whole blood maximum concentrations, and total lymphocyte counts at the first month after transplantation. REJ+ patients had significantly lower lymphocyte maximum levels at 2 and 3 months (59 ± 34 and 33 ± 9 pg/Lc) and higher total lymphocyte counts (0.00204 ± 0.00078 x 109/L and 0.00203 ± 0.00022 x 109/L) when compared with their REJ- counterparts (87 ± 56 and 63 ± 30 pg/Lc, P < .05 and P < .007) and (0.00137 ± 0.00074 x 109/L and 0.0015 ± 0.0006 x 109/L, P < .02 and P < .003) respectively. Whole blood maximum concentrations were significantly higher in patients in the REJ+ group (2050 ± 623 vs 1414 ± 536 ng/mL, P < .02) at 2 months. At 3 months, the 2 groups were comparable (1158 ± 340 vs 1365 ± 525 ng/mL, P = NS). Conclusions: These results suggest that acute rejection is associated with a relatively low cyclosporine-A lymphocyte maximum level and high total lymphocyte count in the early posttransplant period. Cyclosporine-A whole blood maximum concentration failed to correlate with clinical outcome. Cyclosporine-A lymphocyte maximum level seems to offer a more reliable alternative than does whole blood maximum concentration for cyclosporine-A monitoring in patients with kidney transplantation.Item Intravenous Mycophenolate Mofetil with Low-Dose Oral Tacrolimus and Steroid Induction for Live Donor Liver Transplantation(Başkent Üniversitesi, 2005-12) Jain, Ashok; Mohanka, Ravi; Orloff, Mark; Abt, Peter; Kashyap, Randeep; Kelley, Mark; Burlee, Kari; Bozorgzadeh, AdelObjectives: Mycophenolate mofetil (MMF) is used in liver transplantation (LTx) to reduce rejection, nephrotoxicity, neurotoxicity, and the need for steroids. Lower trough concentrations and bioavailability have been reported with oral MMF in first week after LTx. These parameters improve after the first month postoperatively. Previously published studies have used oral formulations of MMF. In this study, we sought to examine survival, rejection, and nephrotoxicity rates using IV MMF in live donor liver transplantation (LDLT). Patients and Methods: Twenty-eight patients (mean age, 50.1 years; 15 men, 13 women) were examined between January 2000 and January 2004 with a mean follow-up of 17 months for survival, rejection, and renal function. Results: Four patients died at 2, 5, 8, and 18 months after LDLT from sepsis (n = 3) and recurrent hepatocellular carcinoma (n = 1). There were no retransplants; hence, patient and graft survival rates were the same (82.4%). Three patients (10.7%) experienced acute cellular rejection requiring treatment. The mean serum creatinine level prior to LDLT was 0.9 ± 0.4 mg/dL, which remained stable throughout the study. One patient required hemodialysis during the perioperative period for 8 days. Conclusions: In the current study, we demonstrate a new strategy of IV MMF administration with low-dose tacrolimus that provides for lower rates of acute rejection, better preservation of renal function, and one that is better tolerated compared with historical treatments after LTx.Item Induction Therapy(Başkent Üniversitesi, 2005-06) Bakr, Mohamed A.Transplantation is a suitable option for patients with end-stage organ failure. Many immunosuppressive agents are available, and this may pose difficulty in choosing an appropriate combination for maintenance therapy, treating episodes of acute rejection of varying severities, and tailoring therapies for specific patients. Induction therapy strategies are accomplished either by relatively high doses of conventional immunosuppressants or by using poly- or monoclonal antibodies. These antibodies are an integral part of transplant medicine today. The rationale for antibody therapy aims at augmenting immunosuppression, ensuring that delayed introduction of calcineurin inhibitors is safe, encouraging steroid withdrawal, and facilitating treatment of patients sensitized to human leukocytic antigens in addition to its crucial role in immunologic conditioning either by tolerance induction or alternatively minimizing the immunosuppressive drugs. Different trends in induction therapy initially consisted of anti-thymocyte globulin, then anti-CD3 Orthoclone, and finally anti-CD20, 25, and 52 agents. Induction therapy is associated with beneficial short- and long-term outcomes when increased risk of adverse effects related to immune system suppression are an issue, especially from cytomegalovirus and lymphomas.