Başkent Üniversitesi Makaleler
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Item Cyclosporine Therapeutic Monitoring With Cmax in Kidney Transplant Recipients: Does it Fit for All Populations?(Başkent Üniversitesi, 2008-12) El-Agroudy, Amgad E.; Ghoneim, Mohamed A.; Nassar, Mohamed; Ismail, Amani M.Background: We sought to assess whether the single cyclosporine concentration taken 2 hours after administration (C2) is a good parameter to predict a drug’s maximal concentration (Cmax) value in Egyptian kidney transplant recipients Materials and Methods: Fifty stable Egyptian kidney transplant recipients with a previously diagnosed schistosomal infection were compared with 50 Egyptian kidney transplant recipients without a schistosomal infection regarding cyclosporine concentrations at time 0 (trough), and then at 1.5, 2, 2.5, 3, and 3.5 hours after a dose of cyclosporine. We used a linear regression analysis to assess any statistically significant differences between the different cyclosporine time concentrations and drug dosages Results: Patients in the schistosomal group had significantly lower C2 levels (511 ± 118 nmol/L) compared with those in the nonschistosomal (control) group (669 ± 213 nmol/L) (P < .05), whereas the C2.5 level was significantly higher (730 ± 215 and 527 ± 129 nmol/L, respectively; P < .05). A significant linear regression relation was determined for only C2.5 in the schistosomal group with both morning cyclosporine dose and cyclosporine dose expressed as mg/kg/d (P = .0123, r = .573018). Conclusions: Egyptian patients have special characteristics with regard to drug absorption and metabolism, mostly owing to schistosomal infection, and they may need the use of C2.5 to monitor cyclosporine. If confirmed by subsequent, larger studies, our findings may have a significant effect on our understanding and management of cyclosporine immunosuppression in clinical renal transplants with persons of different ethnicities.Item Prevalence of Cryoglobulinemia and Autoimmune Markers in Liver Transplant Patients(Başkent Üniversitesi, 2008-09) Garrouste, Cyril; Rostaing, Lionel; Blancher, Antoine; Durand, Dominique; Lavayssière, Laurence; Esposito, Laure; Boulestin, Anne; Kamar, NassimObjectives: To examine the prevalence of cryoglobulinemia and autoimmune markers in stable liver transplant recipients and to determine risk factors and clinical impact. Materials and Methods: Ninety-two liver transplant recipients were tested for cryoglobulinemia, hepatitis B and C, complement C3, complement C4, CH50, antinuclear antibodies, anticytoplasmic neutrophil antibodies, anticardiolipid antibodies, rheumatoid factors, and lymphocyte subpopulations. Liver, renal, and hematology tests were done. Immunosuppressive regimens were based on calcineurin inhibitors in 94.6% of the patients. Results: Cryoglobulinemia was present in 18 patients (19.5%) with characteristics of type II in 27.7%, type III in 61.3%, and indeterminate in 11%. Cryoglobulinemia was present in 55.5% of patients with positive hepatitis C virus serology compared with 35.86% of patients with negative hepatitis C virus serology (P = .06). Among those with hepatitis C virus markers, cryoglobulinemia was present in 30%. Anticytoplasmic neutrophil antibodies were positive in 23% of the patients with cryoglobulinemia, but in only 5.4% of the patients without cryoglobulinemia (P = .006). Albuminemia was significantly lower in patients with cryoglobulinemia (38 ± 4.2 g/L) than it was in patients without cryoglobulinemia (40.2 ± 3.4; P = .05). Cryoglobulinemia was symptomatic in 4 patients (22.2% of all patients). Independent factors associated with cryoglobulinemia were presence of anticytoplasmic neutrophil antibodies, more than 4 HLA incompatibilities, alanine aminotransferase level of 0.68 µkat/L or more, and an albuminemia level greater than 38 g/L. Conclusions: Cryoglobulinemia is frequent after liver transplant and is symptomatic in approximately 20% of all patients.Item Impact of Sirolimus Treatment in Kidney Allograft Recipients With Prolonged Cold Ischemia Times: 5-Year Outcomes(Başkent Üniversitesi, 2008-03) Boratyńska, Maria; Klinger, Marian; Patrzałek, Dariusz; Banasik, MirosławObjectives: Sirolimus, an effective and nonnephrotoxic immunosuppressant, may have an antiproliferative effect on renal tubular cells and increase their apoptosis, thus hindering the recovery of an injured kidney. The aim of this study was to evaluate the impact of combined sirolimus and cyclosporine therapy on the incidence and duration of delayed graft function and long-term graft function. Materials and Methods: The study group consisted of 23 renal transplant recipients treated with a sirolimus-cyclosporine-prednisone regimen (sirolimus group). The reference group was composed of 23 patients treated with azathioprine-cyclosporine-prednisone. Because of a long cold ischemia time, all the patients were at high risk of developing delayed graft function. Results: There was an equal frequency of delayed graft function in the sirolimus group compared with the reference group (39% vs 34.8%). The duration of delayed graft function was longer in sirolimus group compared with the reference group (21.2 ± 12.2 days vs 6.8 ± 2.5 days) (P < .004). The serum creatinine level at the 12th month was higher in patients with delayed graft function than it was in the remaining patients, independent of the immunosuppression protocol. One and 5-year graft survival rates were 100% and 87% in the sirolimus group, and 95% and 74% in the reference group. The 5-year patient survival rate was 100% in both groups. Conclusions: Sirolimus significantly retards the recovery from posttransplant renal failure, but it does not increase the incidence of delayed graft function. Sirolimus therapy should be initiated after recovery from posttransplant renal failure. Sirolimus treatment is beneficial for long-term graft survival.Item Prevalence and Risk Factors of Renal Dysfunction After Liver Transplant: A Single-Center Experience(Başkent Üniversitesi, 2008-03) Dehghani, Seyed Mohsen; Malek-Hosseini, Seyed Ali; Jalaeian, Hamed; Gholami, Siavash; Taghavi, Seyed Ali Reza; Derakhshan, AliObjectives: Renal dysfunction is one of the most significant complications after liver transplant. It is attributed mainly to nephrotoxicity caused by calcineurin inhibitors. We evaluated the renal functioning in liver transplant recipients alive for at least 6 months after liver transplant. Materials and Methods: One hundred seventy patients (108 male [63.5%], 62 female [36.5%]; mean age, 31.4 ± 13.3 years; age range, 13-61 years) were included in this study. Patients who had undergone a liver transplant between 1994 and 2006 at the Organ Transplantation Center of the Shiraz University of Medical Sciences in Shiraz, Iran, and had been alive for at least 6 months after surgery were included. Data were collected regarding age, sex, body mass index, underlying liver disease, graft type, immunosuppressive medications, serum creatinine levels, and glomerular filtration rate before, 1, and 6 months after liver transplant. Renal dysfunction was defined as a serum creatinine level above 132.6 µmol/L or a glomerular filtration rate less than 60 mL/min/1.73 m2, based on our reference range. Glomerular filtration rate was calculated using the Schwartz formula (glomerular filtration rate mL/min/1.73 m2 = K × Ht (cm) / Cr mg/dL). Data were analyzed with SPSS software. Results: The mean follow-up was 25.9 ± 23.5 months (range, 6-156 months). The main indications for liver transplant were cryptogenic cirrhosis (n=42), hepatitis B infection (n=34), autoimmune cirrhosis (n=30), Wilson’s disease (n=21), and primary sclerosing cholangitis (n=18). The mean pretransplant glomerular filtration rate was 93.7 ± 35.6 mL/min/1.73 m2. The mean glomerular filtration rates in the first and sixth months after liver transplant were 81.6 ± 29.3 mL/min/1.73 m2 and 83.6 ± 32.9 mL/min/1.73 m2. Sex, body mass index, type of immunosuppressive medication, and underlying liver disease were not predictors of renal dysfunction (P > .05). Posttransplant renal dysfunction was significantly more common in older patients (ie, those aged 38.8 years and older) (P = .0001) and those with a family history of renal disease (P < .05). Conclusions: Renal dysfunction may be a significant problem for patients after liver transplant, and early detection of renal dysfunction in patients after liver transplant is important. Of all the risk factors studied here, only older age and family history of renal disease were correlated with development of renal dysfunction after liver transplant.Item The Cairo Kidney Center Protocol for Rapamycin-based Sequential Immunosuppression in Kidney Transplant Recipients: 2-Year Outcomes(Başkent Üniversitesi, 2007-12) Barsoum S. , Rashad; Morsy, A. Ahmed; Iskander, Irene R.; Morgan, Manal M.; Fayad, Tarek M. F.; Atalla, Nasr T.; Wafik, Hani; Grace, Renne A.; Adel, Noha; Khalil, Soha S.Objective: This study examines the outcomes of de novo kidney transplants treated by a sequential protocol, designed to target the succession of immunologic events following engraftment. Subjects: A total of 113 sequential live-donor recipients were randomized into 2 arms. Patients in arm A received prednisolone, cyclosporine, and sirolimus for 3 months (phase 1), followed by replacement of cyclosporine with mycophenolate mofetil (phase 2). Those in arm B (controls) received prednisolone/cyclosporine/mycophenolate mofetil throughout the study. The primary endpoints were patient and graft survival rates at 2 years. Secondary endpoints included biopsy-proven acute rejection, early and late graft function, hypertension, and adverse reactions. Results: The 2-year intent-to-treat patient and graft survival rates (95.8% vs 91.4% and 94.6% vs 90.2%) were numerically but not significantly higher in arm A. The overall incidence of biopsy-proven acute rejection was numerically lower (13.5% vs 18.9%), yet it occurred exclusively with cyclosporine C2 levels below 770 ng/mL (P = .28). Mean time for serum creatinine to reach 132 µmol/L was significantly longer in arm A (7.3 vs 2.9 days). Graft function at 2 years (eGFR, 70.2 vs 55.9 mL/min) and number of drugs needed to control blood pressure (mean 1.7 vs 2.25) were significantly more favorable in group A. Significant adverse effects for patients in arm A included proteinuria (36.8% vs 18.6%), hyperlipidemia (peak cholesterol > 7.75 mmol/L in 32.9% vs 23.7% of patients) and thrombocytopenia (platelet count < 100 × 109/L in 32.9% vs 13.5 % of patients). Conclusions: The described protocol reduced the incidence of biopsy-proven acute rejection in patients after kidney transplant, particularly in those with adequate cyclosporine blood levels. Despite the significantly higher incidence of certain adverse effects (ie, delayed graft function, proteinuria, hyperlipidemia, and transient thrombocytopenia), patient and graft survival rates at 2 years were numerically, though not statistically, improved in patients in arm A. At 2-year analysis, compared with patients in the control arm (arm B), graft function significantly improved in patients in arm A, and the number of drugs needed to control blood pressure was significantly lower.Item Treatment of Cyclosporine-Induced Gingival Overgrowth with Azithromycin-Containing Toothpaste(Başkent Üniversitesi, 2006-06) Argani, Hassan; Pourabbas, Reza; Hassanzadeh, Davood; Masri, Marwan; Rahravi, HoomanObjectives: Gingival overgrowth is a complication of cyclosporine therapy following organ transplantation. Oral azithromycin is frequently used to treat this complication. This study examined the efficacy of local azithromycin, in the form of toothpaste, against cyclosporine-induced gingival overgrowth. Materials and Methods: Twenty stable renal transplanted patients (10 men and 10 women) with gingival hyperplasia were randomly assigned to a test group and a control group. Azithromycin-containing toothpaste had 85 mg azithromycin per gram of toothpaste. Both toothpastes were prescribed b.i.d., each time using 1.5 cm, for 1 month. All participants received scaling, root planing, polishing, and oral hygiene instructions, at least 4 weeks prior to initiation of the study. Gingival overgrowth index, bleeding on probing, blood urea nitrogen, creatinine, and serum cyclosporine levels were measured at baseline, and then again in the second and fourth weeks after tooth brushing. Patient satisfaction with the toothpastes was evaluated by a visual analogue scale. The stability of clinical responses was followed for 3 months after cessation of the toothpastes. Results: Gingival overgrowth index decreased significantly in the azithromycin-containing toothpaste group (from 1.1 ± 0.56 to 0.51 ± 0.47, P < .001); however, in the control group, this decrease was not significant (P = .22). Bleeding on probing also decreased significantly in patients in the azithromycin-containing toothpaste group compared with controls (P = .001). When compared with baseline levels, trough levels of cyclosporine, blood urea nitrogen, and creatinine did not change in either of the groups. Patients in the control group were more satisfied with the toothpaste than were patients in the test group (53 vs 38). Conclusions: Azithromycin-containing toothpaste is an effective, simple, and noninvasive treatment for cyclosporine-induced gingival overgrowth.Item Causes of Acute Thrombotic Microangiopathy in Patients Receiving Kidney Transplantation(Başkent Üniversitesi, 2004-12) Jumani, Abdul; Hala, Kfoury; Tahir, Saadi; Al-Ghamdi, Ghormullah; Al-Flaiw, Ahmed; Hejaili, Fayez; Qureshi, Junaid; Raza, Hammad; Ghalib, Muhammed; Al-Khader, AbdullahObjectives: Thrombotic microangiopathy is a well-known problem in patients following renal transplantation. In postrenal transplantation, thrombotic microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to determine the causes of thrombotic microangiopathy in a population of renal transplantation recipients and discuss the literature. Materials and Methods: We investigated the causes of thrombotic microangiopathy during a 1year period, from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh, Saudi Arabia, by reviewing the slides of all transplant biopsies (n = 25) performed during this interval. Pre- and posttransplant crossmatching was done when possible. Results: Five cases of thrombotic microangiopathy were found. Three of these cases were from the 25 transplantations performed at King Fahad National Guard Hospital, while the other 2 transplantations had been performed abroad and were referred to us for follow-up. Three cases were related to cyclosporine, and 1 case was secondary to both cyclosporine and tacrolimus. The fifth case had features of thrombotic microangiopathy related to an antiphospholipid syndrome in a patient with systemic lupus erythematosus. Conclusions: In the literature, the most-frequent cause of hemolytic uremic syndrome in patients following renal transplantation is recurrence of the hemolytic uremic syndrome. Other causes include drug-related (cyclosporine, tacrolimus) toxicity, procoagulant status, and antibody-mediated rejection. We found that the most-frequent cause of thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In the current study, the frequency of thrombotic micro-angiopathy was similar to the percentage reported in the literature (20%).Item Dişeti Büyümesi Olan Böbrek Transplantasyonu Geçirmiş Hastalarda Difleti T Hücre Altgruplarının Karşılaştırılması(Başkent Üniversitesi, 2005-01) N. Özmeriç; S.E. Gültekin; Ö. Ünlü; E. Ayhan; T. Oygür; B. BalAmaç: Dişeti büyümelerinin, siklosporin-A grubu ilaçların yan etkileri olarak ortaya çıktığı bilinmektedir. Siklosporin-A grubu ilaçların immunsupresif etkileri, mitojen veya antijenle indüklenen T hücre proliferasyonunun baskılanmasına dayanmaktadır. Bu çalışmanın amacı, siklosporin kullanan böbrek transplantasyon hastaları ile sistemik sağlıklı erişkin periodontitis hastalarının dişeti T hücre altgrup sayıları ve dağılımlarını karşılaştırmaktır. Materyal ve Metod: Dişeti büyümesi gözlenen 12 böbrek transplantasyon hastasının ve 12 sistemik olarak sağlıklı erişkin periodontitisli hastanın, klinik periodontal ölçümleri yapıldıktan sonra dişeti biyopsileri elde edildi. Her iki gruptan alınan biyopsilere immunohistokimyasal boyama yapıldı ve CD4(+), CD8(+) hücreleri değerlendirildi. Sonuçlar: CD4(+) ve CD8(+) hücre sayıları, böbrek transplantasyonu geçiren hasta grubunda ve erişkin periodontitisli grupta benzer bulundu. Her iki grupta da dominant T hücre immunofenotipi CD8(+)olarak tespit edildi. Yorum: Böbrek transplantasyonu yapılan hastalarda kullanılan immunsupresif ilaçların, periodontal kaynaklı inflamasyonun T hücre aracılı immunopatogenezini değiştirmediği ve dişeti büyümelerinin başlangıcı ve ilerlemesinin primer olarak, T hücreleri ile ilişkili olmadığı düşünülmüştür. Comparison of Gingival T-Cell Subgroups in Renal Transplant Recipients with Gingival Overgrowth: An Immunohistochemical Study Objective: Gingival overgrowth is a reported side effect of cyclosporine A (CsA) administration. The immunosuppressive effect of CsA is mainly due to inhibition of mitogen- or antigen-induced T-cell proliferation. This study was undertaken to determine whether CsA affects the distribution and sizes of gingival T-cell subpopulations in adult renal transplant recipients with periodontitis. Materials and Methods: After performing clinical periodontal measurements, gingival biopsies were obtained from 12 adult renal transplant recipients and 12 systemically healthy adults with periodontitis. Frozen sections of gingival biopsies from both groups were immunohistochemically stained to identify CD4(+) and CD8(+) cells. The cell types were quantified using an ocular grid and taking the epithelial basal membrane as a reference. A total of 96 sections from 24 gingival samples were examined. The numbers of these cells per 1-mm basal membrane length were counted, the means for each group were calculated. Results: The mean numbers of CD4(+) and CD8(+) cells in the two study groups were not significantly different. The dominant T-cell immunophenotype in both groups was CD8(+). Conclusion: The results suggest that use of CsA in adult renal transplant recipients does not significantly alter the immunopathogenesis of periodontal inflammation with respect to T-cell counts in gingival tissues. Quantitative analysis revealed no changes in T-helper and T-suppressor cell counts in the group that was receiving standard CsA immunosuppression.