Başkent Üniversitesi Makaleler
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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 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 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 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%).