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Allogeneic stem cell transplantation (SCT) offers a potential cure for some hematological malignancies. For those patients without a family donor, unrelated donor (MUD) registries serve for identifying the best donor. In the present study, we aimed to give a cross-sectional report of our registry's activity and experience as the first established national MUD registry in the country. The study is retrospective and covers the period of 2016 to 2019. A total of 1855 donor searches were performed, and 642 were included in the study. All data were electronically obtained from the institutional database system. All SCTs were either 10/10 or 9/10 HLA matched and originated from an international registry. The most preferred stem cell source was peripheral blood (70.2%). A quarter of transplants were performed using bone marrow, and cord blood was used with a rate of 1.4%. The pandemic-related problems were similar for the other two national registries. During the pandemic, 71 of 432 patients who were searched for donors underwent stem cell transplant(SCT). The low number was related mostly with postponing of SCTs and/also difficulties in continuing of volunteering and in achievement of stem cells from international registry. During the Covid19 pandemic, the SCT activity of centers decreased according to the national, and international guidelines. The study revealed an organized, and multidirectional capacity of the registry and also the adaptation to unpredicted conditions such as pandemic. On the other hand, there is a need for more effective strategies for donor recruitment and retention programme.

Background: Current knowledge on the ideal local anesthetic concentration for the ultrasound-guided transversus abdominis plane block (TAPB) in pediatrics is scarce. The purpose of this study is to compare the efficacy of US-guided TAPB at two different concentrations of bupivacaine in pediatrics undergoing unilateral inguinal hernia repair. Methods: After random allocation, 74 children aged 1-8 were randomized to receive US-guided TAPB by using 1 mg.kg-1 bupivacaine as either 0,25% (0,4 ml.kg-1) (Group 1) or 0,125% (0,8 ml.kg-1) (Group 2) concentration. All blocks were performed under general anesthesia, immediately after the induction, unilaterally with an intercostoiliac approach. All subjects received intravenous 15 mg/kg paracetamol 0.15 mg/kg dexamethasone and 0.1 mg/kg ondansetron intraoperatively. The primary outcome was the efficacy and is assessed by postoperative FLACC behavioral pain assessment score at 15’, 30’, 45’, 1h, 2h, 6h, and 24h. The secondary outcomes were to assess the total dose of rescue analgesic consumption, length of hospital stay, the incidence of side effects, complications and satisfaction levels of the patients’ parents and the surgeons. Results: Sixty-four children were recruited for the study. Postoperative pain scores were equal between the two groups. There was no need for a rescue analgesic in any group after the postoperative 6thhour. No local or systemic complication or side effect related to anesthesia or surgery was reported. Conclusion: TAPB using 1 mg.kg-1 bupivacaine administered as either high volume/low concentration or low volume/high concentration was providing both adequate analgesia and no side effects. TAPB is an effective analgesic technique for children undergoing inguinal hernia repair.

Objective: HLA class I and II alleles are shown to be associated with certain diseases. A restricted numbers of alleles were found to be related to alloimmunisation in thalassemia population. The role of human leucocyte antigens in thalassemia is trend topic. In this study, the aim was to evaluate the differences in HLA frequencies of beta thalassemia patients comparing with healthy controls. Methodology: The data were collected of 100 patients who were diagnosed with beta thalassemia and 100 healthy controls were included in the study. The low resolution HLA-A, -B, -DRB1, tissue group data were performed Istanbul University, Faculty of Medicine, Medical Biology Department HLA typing laboratory. All data were analyzed retrospectively and their HLA allele frequencies were analyzed by SPSS (v22) program. Results: We found an increased frequency of HLA-B*14 (8% versus 2%) and HLA-B*52 (17% versus 2%) compared to the control group (p=0.05, OR=4.26; p

Introduction Early diagnosis of rejection in kidney transplant (KTx) recipients is of paramount importance for long-term graft survival. Cytokines play an important role in rejection via activating T cells. Neutrophil accumulation in the graft indicates cell-mediated rejection. Cellular infiltration is mediated through chemoattractant factors. The aim of this study was to investigate the relationship between graft function and serum levels of interleukin 2 (IL-2) and interleukin 8 (IL-8) in KTx. Method Sixty-five patients undergoing KTx were enrolled in the study. Serum samples of IL-2 and IL-8 were collected the day before the operation, on postoperative days 1 and 7 day, and during the first and third month after the onset of rejection. The enzyme-linked immunosorbent assay method was used to determine the IL-2 and IL-8 values. Results A total of 9 (13.8%) patients had rejection documented on biopsy samples. Fifty-six patients had stable graft function (SGF). IL-2 and IL-8 values before KTx of both the rejected and SGF patients were not statistically different. Univariate analysis revealed that IL-2 and IL-8 were correlated with rejection (P = .046, P = .015). IL-8 levels were higher in the rejection group compared to the SGF group on the seventh day and first month postoperatively (P = .023, P = .038). The rejection group maintained higher levels of IL-8 for 11 days (range: 7–30) compared to the SGF group (P = .002) and the IL-8 levels correlated with serum creatinine levels (r = 0.621, P = .001). IL-2 levels were higher in the rejection group on days 1 and 7 compared to the SGF group (P = .042, P = .031). IL-2 and IL-8 levels were correlated with low eGFR in the third month in the rejection group (r = 0.421, P = .037; r = 0.518, P = .008). Conclusion Determining the cytokine levels in the early post-KTx period may be helpful in tailoring immunosuppressive regimens in patients with a risk of rejection.

Objective: Hematopoietic stem cell transplantation (HSCT) is an important therapy for hematological diseases. One of the most significant complications of HSCT is graft versus host disease (GVHD), and major histocompatibility complex (MHC) is well known to affect GVHD and graft rejection. This study aimed to examine the effect of human leukocyte antigens (HLA) on the incidence of GVHD development in patients with leukemia. Methods: The association between HLA and GVHD formation was evaluated in 57 patients with HSCT with HLA-identical sibling donors, of whom 37 were boys and 20 were girls with a mean age of 10.11 years. All patients were diagnosed with leukemia; acute myeloid leukemia (n=33), acute lymphoblastic leukemia (n=15), and chronic myeloid leukemia (n=9). Transplantation pairs were worked for HLA-A, -B, -C, and -DRB1 alleles. Class I HLA antigens were investigated using Terasaki microlymphocytotoxicity, whereas class II HLA alleles with polymerase chain reaction - sequence-specific amplification method. Results: The frequency of developing GVHD in patients with HSCT was found to be 17.5% (n=10). HLA-DRB1∗04 allelic frequency [p=0.024, odds ratio (OR): 4.87] was found to be higher in patients who developed GVHD. However, the HLA-DRB1∗11 allelic frequency (p=0.031, OR: 0.12) was lower in patients who developed GVHD compared to patients who did not develop GVHD. Furthermore, HLA-B38 (p=0.002) and HLA-B41 (p=0.002) antigens were found only in patients who developed GVHD. The frequencies of the HLA-A26 allele (p=0.12) and the HLADRB1∗11 allele (p=0.037, OR: 4.0) were higher in patients with relapse after HSCT; however, the frequencies of the HLA-A2 allele (p=0.033, OR: 0.19) was lower in patients who relapsed after HSCT. Conclusion: This study assessed the relationship of HLA class with GVHD, relapse, and survival in children after HSCT in pediatric patients with leukemia. Amaç: Hematopoetik kök hücre nakli (HKHN), hematolojik hastalıklar için önemli bir tedavidir. HKHN’nin en önemli komplikasyonlarından biri, graft-versus-host hastalığıdır (GVHH) ve büyük doku uyumluluk kompleksinin (major histocompatibility complex-MHC) GVHH ve greft reddini etkilediği iyi bilinmektedir. İnsan lökosit antijenleri (human leukocyte antigen - HLA) tipinin lösemili hastalarda GVHH insidansı üzerindeki etkisini incelemeyi amaçladık. Gereç ve Yöntem: HLA uyumlu kardeş donörleri ile HKHN olan 57 hastada HLA ve akut, kronik GVHH oluşumu arasındaki ilişki değerlendirildi. Çalışmaya yaş ortalaması 10,11 olan 37 erkek ve 20 kız dahil edildi. Tüm hastaların tanıları; Akut myeloid lösemi (n=33), akut lenfoblastik lösemi (n=15), kronik myeloid lösemi (n=9) idi. Tüm nakil kardeş çiftleri HLA-A, -B, -C, -DRB1 allelleri için tiplendirildi. Sınıf I HLA antijenleri Terasaki mikrolenfositotoksisite kullanılarak saptandı ve sınıf II HLA allelleri polimeraz zincir reaksiyonu-diziye özgü primerler (polymerase chain reaction with specific primer sequence) yöntemi ile analiz edildi. Bulgular: HKHN uygulanan hastalar arasında GVHH insidansı %17,5 (n=10) olarak bulundu. HLA-DRB1*04 allelik frekansı [p=0,024, risk oranı (OR): 4,87] GVHH gelişen hastalarda daha yüksekti. Bununla birlikte, HLA-DRB1*11 allelik frekansı (p=0,031, OR: 0,12), GVHH gelişen hastalarda, GVHH geliştirmeyen hastalara göre daha düşüktü. Ayrıca, HLA-B38 (p=0,002) ve HLA-B41 (p=0,002) antijenleri sadece GVHH gelişen hastalarda bulundu. HLA-A26 alelinin (p=0,12) ve HLA-DRB1*11 alelinin (p=0,037, OR: 4,0) frekansları daha yüksekken, HLA-A2 allelinin frekansları (p=0,033, OR: 0,19) HKHN sonrası nükseden hastalarda daha düşük olarak saptandı. Sonuç: Bu çalışma, lösemili pediatrik hastalarda HKHN sonrası çocuklarda HLA sınıfının GVHH, relaps ve sağkalım ile ilişkisini değerlendiren çalışmadır.

INTRODUCTION AND OBJECTIVE:Kidney transplantation (KTx) has been established as the optimal renal replacement therapy for end-stage renal disease, with a longer life expectancy, better quality of l...

Objective Surgical stress combined with general anaesthesia (GA) suppresses the immune system and leads to cancer cell growth and premature metastasis in major oncological interventions. Epidural analgesia decreases the need for inhalation agents and opioids during surgery by suppressing sympathetic and neuroendocrine responses in the postoperative period. This study aimed to compare the effects of combined general/epidural anaesthesia (GEA)+patient-controlled epidural analgesia (PCEA) and GA+IV patient-controlled analgesia (PCA) on serum tumour necrosis factor-alpha TNF-α), interleukin-1 beta (IL-1β) and interferon-gamma (IFN-γ) levels in patients undergoing radical cystectomy. Methods Sixty-five patients were enrolled in this prospective study. Patients were randomly enrolled to the GEA group, i.e., combined GEA+ PCEA (0.1% bupivacaine+1 μg mL-1 fentanyl), and the GA group, namely combined GA+IV PCA (0.03 mg mL-1 morphine). To evaluate the cytokine response, blood samples were collected at preoperative, postoperative 1st and 24th hours. Results There was no statistically significant difference in serum TNF-α, IL-1β and IFN-γ levels between groups GA and GEA at preoperative and postoperative 1st hour and 24th hour. Total remifentanil consumption was significantly lower and length of hospital stay was significantly shorter in the GEA group than in the GA group (p Conclusion There is no difference between two anaesthesia methods in terms of serum cytokine levels; however, combined GEA+PCEA technique appeared to be superior to GA+IV PCA because of lower intraoperative narcotic analgesic consumption and shorter hospital stay.

Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression. Clinically relevant drug-drug interactions have been described between immunosuppressive drugs. In the present study, we investigated the drug interaction between MPA and lansoparazole or rabeprazole and the impact of CYP2C19 polymorphisms on these drug interactions after renal transplantation.A total of 125 renal transplant patients taking MPA derivatives between 2012 and 2016 were included in this study. The 125 patients were divided into 6 groups: MMF/tacrolimus/steroid together with lansoprazole or rabeprazole; MYF/tacrolimus/steroid together with lansoprazole or rabeprazole and without PPI. The single nucleotide polymorphisms of CYP2C19 were determined by the polymerase chain reaction-restriction fragment length polymorphism. Plasma concentrations of MPA were measured by cloned enzyme donor immunoassay. Clinical parameters such as incidence of delayed graft function and acute rejection, the rate of change of serum creatinine, toxicity, and gastrointestinal adverse effects were analyzed retrospectively.The mean concentrations of MPA in the MYF group were higher than those in the MMF group. The mean dose-adjusted blood concentration of MPA coadministered with lansoprazole was lower than that of MPA with rabeprazole or without PPI in MMF and MYF groups (P .05). In patients with the CYP2C19*2/*2 genotype, the mean concentrations of MMF with lansoprazole were significantly lower than those with rabeprazole with MMF or without PPI (P .05). Gastrointestinal side effects were significantly higher in MMF with lansoprazole group than in MYF with lansoprazole group (P .05). However, no differences were found according to genotype distribution in all groups (P.05).Polymorphisms in CYP2C19 are related to the metabolic oxidation of drugs to varying degrees. Both genetic and clinical factors in pharmacokinetics may help to make further progress toward individualized therapy to yield maximum efficacy with minimal side effects.

Human leukocyte antigen (HLA) allo-immunization is caused by various events such as blood transfusions, pregnancies, or organ transplantations, which can lead to sensitization. In this retrospective study, we evaluated different sensitization models and their effects on panel-reactive antibody (PRA) profiles of renal transplantation candidates.Anti-HLA class I/II antibody screening tests were performed in 906 renal transplantation candidates with the use of a microbead-based assay (Luminex).Two hundred ninety-seven (32.8%) of the patients were determined as positive in terms of PRA, and 609 (67.2%) were negative. Sensitized and non-sensitized patients were compared separately in terms of each sensitization type. The anti-HLA class I, II, and I+II positivity rates in patients sensitized only by blood transfusion were 13.1%, 6.3%, and 14.1%, the rates with pregnancy sensitization were 35.5%, 29%, and 45.2%, and rates with previous transplantation sensitization were 15.6%, 34.4%, and 38.9%, respectively. Prevalence of PRA positivity was significantly higher in patients with previous pregnancy than with transplantation and transfusion (odds ratio, 1.003; 95% confidence interval, 0.441-2.281; P = .031). The risk of developing HLA class I antibodies was higher in pregnancies (P .001), and the risk of developing anti-HLA class II antibodies was higher in patients who had undergone a previous transplantation (P .001). The rate of developing HLA-B antibodies in patients sensitized by pregnancy were significantly higher compared with sensitization after transfusion (P = .015), as was the rate of developing HLA-DQ antibodies in patients sensitized by previous transplantation compared with sensitization through pregnancy (P = .042).In patients who are waiting for kidney transplantation, sensitization by pregnancy and transplantation have a significant impact on development of HLA class I and class II antibodies.

Istanbul Medical Faculty, Department of Medical Biology, as the first EFI-accredited HLA laboratory in Turkey since 1999 has been organizing both national and international quality control tests for HLA typing under the banner of the "Balkan external proficiency testing (BEPT)" encompassing countries from EFI regions 8. The first round of BEPT in 2004 was organized for low-resolution HLA-A,-B typing by molecular methods and 12 centres participated in the exercise. In 2005, low-resolution HLA-DR typing was added, and in 2007, low-resolution HLA-C and DQ typing were added to the exercise and 28 centres participated. In 2015, high-resolution (four digits or higher typing) HLA-A,-B,-C,-DR and -DQ typing added to the exercise and 40 centres participated. In the last 2 years, 2017 and 2018, the number of participating centres increased to 48 and 52, respectively. When the distribution of low-resolution typing methods applied in the exercises were investigated, it was found that 82% of the centres in the first round of BEPT in 2004 used PCR-SSP, whereas in the last round in 2018, 26% of the centres preferred SSP, while the rest used SSO (50%) or SSP and SSO (24%) methods. Methods for high-resolution typing were SBT (41%), NGS (18%), SSO (18%), SSP (6%), SBT + NGS (6%) and SBT + SSP (11%). In 15th trial for BEPT, nomenclature mistake rate was 12%, and erroneous result rate was 6% for HLA samples. The most common mistakes in the exercises were nomenclature mistakes. The EFI Standards Version 7.0 is stated "HLA type can be reported using a hyphen if homozygosity is not proven by family studies." In order to provide standard results among HLA laboratories and since accurate HLA typing leads to significant increase of graft and patient survival, quality control exercises should be performed in all HLA-based tests periodically.

Background In patients with hepatitis C virus (HCV) infection, the activation of the immune system by the virus or viral proteins leads to the production of numerous autoantibodies and clinical manifestations. The objectives of this study were to investigate the relationship between HCV and anti-HLA antibodies, as well as the effect of viremia on the antibody response and of direct-acting antivirals (DAAs) on anti-HLA antibody persistence in patients on the waiting list for a cadaveric kidney transplant. Methods A total of 395 patients from the cadaveric renal transplant waiting list were included in the study. The patients were grouped according to the presence of HCV infection, and patients with HCV positivity were further divided into a spontaneous clearance group and a persistent group. Anti-HLA antibodies were examined before and after treatment of the patients in the persistent group. The One Lambda Luminex method (Thermo Fisher Scientific, Waltham, MA, United States) was used to assess both HLA class I and II alleles and the anti-HLA antibody profile. Results Anti-HLA class I and II antibodies were detected in 48.2% and 55.1%, respectively, of the patients infected with HCV and in 21.8% and 20.4%, respectively, of the patients who were not infected. The level of anti-HLA A3, A11, B72, B52, Cw6, Cw16, DR3, and DQ4 antibodies was significantly higher in the patients infected with HCV. There was no statistically significant difference in class I and II antibody titration between the HCV-infected spontaneous clearance group and the persistent group (class I mean fluorescence intensity [MFI] ± SD: 13,583 ± 6224, 13,450 ± 9540, P = .808; Class II MFI ± SD: 13,000 ± 8673, 8440 ± 8302, P = .317, respectively). There was no significant difference in the class I and class II anti-HLA antibody profile and titration in the persistent group after treatment with DAAs (P > .05). Conclusions The results of this study demonstrated that hepatitis C DAA treatment did not change the anti-HLA antibody profile and titration.

Objectives Renal transplant is the treatment of choice for patients with end-stage renal disease. Ischemiareperfusion damage is a major cause of early renal dysfunction during the perioperative period. Ischemic hypoxic damage increases local inflammation, leading to secretion of cytokines and chemokines. Anesthetic conditioning is a widely described strategy to attenuate ischemia-reperfusion injury. Here, we compared the effects of desflurane and sevoflurane on serum proinflammatory cytokines and urine chemokines in living-donor kidney transplant recipients. Materials and methods Eighty donor-recipient couples were included in this randomized study. Anesthesia maintenance was provided by desflurane or sevoflurane. Patient demographic characteristics, immunologic data, clinical data, and hemodynamic parameters were recorded. Tumor necrosis factor α, interleukins 2 and 8, chemokines 9 and 10, and serum creatinine levels were studied from pretransplant, posttransplant days 1 and 7, and posttransplant months 1 and 3 sample results. Estimated glomerular filtration rates were calculated. Acute rejection episodes and graft loss within 6 months posttransplant were recorded. Results Seventy donor-recipient couples completed the study. There were no significant differences in demographic, immunologic, and clinical data between desflurane and sevoflurane groups (P > .05). Tumor necrosis factor α, interleukin 2, chemokine 9, and chemokine 10 levels were similar preoperatively and on postoperative days 1 and 7 and months 1 and 3 (P > .05). Serum interleukin 8 levels were significantly higher in patients who received sevoflurane on postoperative days 1 (P = .045) and 7 (P = .037). No significant differences were detected in serum creatinine and estimated glomerular filtration rate between groups (P > .05). No graft loss occurred within 6 months posttransplant. Conclusions Although sevoflurane seemed to produce higher interleukin 8 levels posttransplant, both desflurane and sevoflurane had similar effects on posttransplant kidney function. We suggest that both agents have protective effects on ischemic-reperfusion damage in living-donor kidney transplant recipients.

Objectives Schizophrenia (Sch) is a severe and chronic mental illness. Smoking prevalence is higher in patients with Sch than general population. We aimed to investigate the effects of MAOB gene A644G variant on nicotine dependence (ND) and Sch+ND risk in Turkish population and to evaluate by bioinformatic analysis. Methods Present study included 161 individuals with ND, 223 patients with Sch+ND, and 96 non-smoker controls. MAOB A644G variant was analyzed using PCR-RFLP method. As the MAOB gene is located on the X chromosome, each gender was analysed separately. Results The total distributions of AA, AG and GG genotypes of MAOB gene A644G were 44.7%, 22.4% and 32.9% in the ND group, 45.3%, 25.1% and 29.6% in the Sch+ND group and, 44.8, 22.9% and 32.3% in non-smoker controls. No significant differences were observed between groups for the MAOB A644G genotype and allele frequencies when female group compared to male group (p > 0.05). Examination of disease associations of SNPs from each miRNA gene region in GWAS databases yielded results for aging, bipolar disorder, autoimmune, and neurological diseases. Discussion Our results indicate that the MAOB gene A644G variant is not associated with ND and/or Sch susceptibility in the Turkish population. © 2019, Universidade de Sao Paulo. All rights reserved. 2414-50695 This study was supported by Istanbul University BAP (BEK: 2017-25175 and TYL: 2414-50695) program. 2-s2.0-85064121037

Objective: Schizophrenia (Sch) and bipolar disorder (BD) are debilitating chronic psychiatric disorders that are both etiologically and clinically heterogeneous. According to the gathered evidence, multiple mental disorders are accompanied by inflammation. Interferon-γ (IFN-γ), as a regulatory cytokine, is involved in the immune response as a proinflammatory mediator. Several critical physiological functions are regulated and governed by nitric oxide (NO) in the central nervous system. This study aimed to investigate the association between IFN-γ +874T/A and eNOS 894G/T variants and Sch or BD susceptibility. Methods: Blood samples were collected from patients and healthy subjects. IFN-γ +874T/A and eNOS 894G/T variants were genotyped with the PCR-RFLP. We evaluated the patients with some clinical parameters (the duration of the disorder, age of onset, number of hospitalizations, family history, tobacco smoking or drug, alcohol usage). Statistical analyses were performed using the SPSS version. Results: When the genotype distributions and allele frequencies of the IFN-γ +874T/A and eNOS 894G/T in the patients diagnosed with Sch or BD were compared with the control group, there were not found to be significant differences between the groups. When comparing IFN-γ +874T/A and eNOS 894G/T genotype distributions and allele frequencies of Sch or BD patients due to clinical parameters, the genotype distribution of IFN-γ +874T/A in BD patients was significantly different between the groups due to the presence of tobacco smoking (OR: 0.217, 95%Cl: 0.054–0.878; p = 0.032). Conclusion: To the best of our knowledge, this is the first study that examines the association between the IFN-γ and eNOS gene variants and Sch or BD in a Turkish population. Although IFN-γ +874T/A and eNOS 894G/T variants are not considered as candidate genes for Sch or BD, the results indicated that the BD patients carrying IFN-γ +874T/A AA genotype were less susceptible to tobacco smoking in a Turkish population.

Background: Laparoscopic partial nephrectomy, which minimizes renal function loss due to its nephron sparing nature, has become a standard technique among many experienced centers worldwide for surgical treatment of localized kidney tumors. Although partial nephrectomy will remain the gold standard, we need to improve perioperative management and surgical method to prevent postoperative acute kidney injury. Aims: To demonstrate the frequency of the development of postoperative acute kidney injury following laparoscopic partial nephrectomy in patients with healthy contralateral kidney and determine the early predictive effects of serum neutrophil gelatinase-associated lipocalin on ischemia-reperfusion injury and its association with warm ischemia time. Study Design: Cross-sectional study. Methods: Eighty patients were included. We analyzed tumor size, operating time, duration of anesthesia, and warm ischemia time. Serum samples were obtained for measurement of serum creatinine, estimated glomerular filtration rate, and neutrophil gelatinase-associated lipocalin level preoperatively, at the postoperative 2nd hour, and on postoperative days 1 and 2. We used receiver operating characteristic curve for determining the cut-off point of neutrophil gelatinase-associated lipocalin to detect postoperative acute kidney injury. Correlation analysis was performed using Spearman’s test. Results: Twenty-seven patients developed acute kidney injury on postoperative day 2, and the neutrophil gelatinase-associated lipocalin level increased significantly at the postoperative 2nd hour in the acute kidney injury group (p=0.048). For a cut-off of 129.375 ng/mL neutrophil gelatinase-associated lipocalin, the test showed 70.0% sensitivity and 68.3% specificity for the detection of acute kidney injury at the postoperative 2nd hour. For a cut-off of 184.300 ng/mL neutrophil gelatinase-associated lipocalin, the test exhibited 73.3% sensitivity and 63.3% specificity for the detection of acute kidney injury on postoperative day 1. A significant correlation was found between warm ischemia time and neutrophil gelatinase-associated lipocalin level at the postoperative 2nd hour (r=0.398, p=0.003). The creatinine values were significantly higher and the estimated glomerular filtration rates were significantly lower on postoperative days 1 and 2 in the acute kidney injury group compared with those in the non-acute kidney injury group (p

Background: There are differences in pharmacokinetic of mycophenolic acid among individuals. The UGT1A9 enzyme is of special interest since it is the main enzyme involved in the glucuronidation of MPA. Single nucleotide polymorphisms in the UGT1A9 gene may be responsible for individual differences in the pharmacokinetics of MPA. The aim of this study was to explain MPA pharmacokinetics in UGT1A9 1399 C > T polymorphisms in Turkish renal transplant patients. Patients and methods: One hundred and twenty-five living-donor transplant recipients and 100 healthy control subjects underwent UGT1A9 1399 C > T genotyping using polymerase chain reaction–restriction fragment length polymorphism. Concentrations of MPA were determined with Cloned Enzyme Donor Immunoassay (CEDIA). Besides that, all the patients were monitored for acute rejection and graft function during the study period. Results: The UGT1A9 1399 C > T CC, CT, and TT genotype frequencies among patients were, respectively, 68.0%, 23.2%, and 8.8%. The CC, CT, and TT genotype frequencies among controls were, respectively, 63.0%, 23.0%, and 14.0%. There was no significant difference between patients and controls (p = .480, p = .999, p = .286, respectively). At first month, respectively, through blood concentrations of MPA were significantly higher in UGT1A9 1399 C > T TT carriers than in CT and CC carriers (p = .046). The doses for these patients were lower at first month (p = .021). Acute rejection episodes were not associated with the CC vs CT or TT genotypes (p = .064). Conclusions: Our results demonstrated a correlation between the UGT1A9 1399 C > T polymorphism and MPA pharmacokinetics among renal transplant patients. Determination of UGT1A9 polymorphism may help to achieve target of MPA blood concentrations.

Introduction High rates of panel-reactive antibody (PRA) may decrease the chance of kidney transplantation and may result in long waiting periods before transplantation. The calculated PRA (cPRA) is performed based on unacceptable HLA antigens. These antigens are identified by a program that was created based on the antibodies that developed against the HLA antigens circulating in serum and on the risk of binding of these antibodies to antigens. The antigen profile of the population and antigen frequencies can be measured, and more realistic cPRA positivity rates may be obtained using this method. Materials and Methods We developed a program based on the HLA antigens of 494 blood donors in 2 European Federation for Immunogenetics–accredited Tissue Typing Laboratories in Turkey. Next-generation sequencing–based tissue typing (HLA-A, -B, -C, -DR, -DQ, 4 digits) of the samples was performed. The PRA screening test was performed on 380 patients who were waiting for organ transplant from a cadaver in Istanbul Faculty of Medicine. The single antigen bead assay testing was performed to identify the antibody profiles on 48 hypersensitized patients. Results The PRA testing results using the current methods were 44.6% ± 18.5%, and the cPRA rate was 86.2% ± 5.1%. The mean PRA positivity of the sensitized patients using the current methods was 44.6%; however, the rate was 86.2% using the cPRA. Discussion cPRA shows the rate of the rejected donors according to all unacceptable antigens. The need for a list of unacceptable antigens in place of the PRA positivity rate is a real change in the sensitization-dependent calculation as cPRA positivity rate. Conclusion In principal, implementation of cPRA will encourage many centers and laboratories to adopt a standard measurement of sensitization in Turkey. It will increase the chances of better donor match, particularly for hypersensitized patients, by the creation of an unacceptable mismatch program using cPRA software.

Background Tacrolimus, a calcineurin inhibitor, is prescribed to prevent allograft rejection in renal transplantation. Tacrolimus not only has a narrow therapeutic index, but also shows significant interindividual differences. The absorption and metabolism of this drug are affected by multidrug resistance (MDR) 1 gene polymorphisms that correlated with single-nucleotide polymorphisms (SNPs) affecting in vivo P-glycoprotein activity. This study investigated associations of MDR1 gene C3435T polymorphism with tacrolimus blood concentrations and dose requirements as well as acute rejection episodes among Turkish renal transplant patients. Methods One hundred living-donor transplant recipients and 150 healthy control subjects underwent C3435T genotyping using polymerase chain reaction–restriction fragment length polymorphism. Blood concentrations of tacrolimus were determined with the cloned enzyme donor immunoassay. Results The CC, CT, and TT genotype frequencies among patients were, respectively, 44.0%, 33.0%, and 23.0% versus 36.7%, 43.3%, and 20.0% among control subjects. There was no significant difference between ( P = .061; P = .102; P = .211; respectively). The ratio of blood concentration to dose of tacrolimus for patients with mutant homozygous 3435 TT genotype was higher than that of wild-type 3435 CC genotype homozygous individuals. The doses for these patients were lower at 1, 3, and 12 months ( P = .048; P = .03; P = .041, respectively). There were no significant differences between the groups regarding coprescription of drugs that affect tacrolimus concentrations, such as diltiazem. Acute rejection episodes were not associated with the CC vs CT or TT genotypes: odds ratio (OR), 0.517 (95% confidence interval [CI], 0.190–1.407; P = .192); OR 1.558 (95% CI, 0.587–4.136; P = .372); OR 1.346; (95% CI, 0.456–3.968; P = .590), respectively. Conclusions Determination of MDR1 polymorphism may help to achieve target of tacrolimus blood concentrations.

Mixed lymphocyte culture (MLC) is one of the routine tests performed prior to hematopoietic stem cell transplantation (HSCT) as a predictive assay for assessing the quality of donor matching and graft-versus-host disease (GVHD). The stimulation index is one of the formulas of the MLC test, and it is used for evaluation of matching between donor and recipient. Modified MLC (mMLC) test is produced by adding various cytokines to the MLC test, and increased sensitivity has been reported with this modification.The importance of the stimulation index values in MLC and mMLC tests was evaluated in 59 patients who received HSCs from human leukocyte antigen-identical sibling donors. In the mMLC test, cytokines were added as interleukin (IL)-2, IL-2 + IL-4 and IL-2 + interferon (IFN)-gamma + tumor necrosis factor (TNF)-alpha. Stimulation index values in mMLC test were compared with stimulation index values in MLC test.Twenty-three (39%) patients developed GVHD. When evaluated in terms of stimulation index1 patients, in MLC, 55% of the patients developed GVHD (p=0.229), whereas these values were 75% in the IL-2 added mMLC test (p=0.035), 100% in the IL-2 + IL-4 added mMLC test (p=0.076) and 85.7% in the IL-2 + IFN-gamma + TNF-alpha added mMLC test (p=0.015).mMLC increased the sensitivity of the test. The relation between the positive results and evidence of GVHD after transplantation was found significant.AMAÇ: Mikst lenfosit kültür testi hematopoetic kök hücre naklinden önce, donör uyumunu ve graft versus host hastalığını önceden belirlemek amacı ile yapılan bir testtir. Stimülasyon indeksi mikst lenfosit kültür testinde kullanılan formüllerden biridir ve alıcı ile verici arasındaki uyumu belirlemek için yapılır. Modifiye mikst lenfosit kültür testi ise mikst lenfosit kültür testine çeşitli sitokinlerin ilave edilmesiyle yapılır ve yapılan bu değişiklikle duyarlılıkta artış olduğu saptanmıştır. YÖNTEMLER: HLA uyumlu donörden hematopoetik kök hücre nakli yapılacak 59 hastada Mikst Lenfosit Kültür ve Modifiye Mikst Lenfosit Kültürdeki stimülasyon indeksi değerlerine bakılmıştır. Modifiye mikst lenfosit kültür testinde sitokinler interlökin-2, interlökin-2 + interlökin-4 ve interlökin-2 + interferon-gama + tümör nekrozis faktör-alfa şeklinde eklenmiş ve modifiye mikst lenfosit kültüründeki stimülasyon indeksi değerleri, mikst lenfosit kültüründeki stimülasyon indeksi değerleriyle karşılaştırılmıştır.Yirmi üç hastada (%39) graft versus host hastalığı oluşmuştur. Mikst lenfosit kültürde stimülasyon indeksi1olan hastalara bakıldığında hastaların %55'inde graft versus host hastalığı görülmüştür (p: 0,229). Bunun yanı sıra interlökin-2 ilavesi ile yapılan modifiye mikst lenfosit kültür testinde stimülasyon indeksi1 olan hastaların %75'inde (p=0,035); interlökin-2 + interlökin-4 ilavesi ile yapılan modifiye mixt lenfosit kültür testinde stimülasyon indeksi1 olan hastaların %100’ünde (p=0,076) ve interlökin-2 + interferon-gama + tümör nekrozis faktör-alfa ilavesi ile yapılan modifiye mixt lenfosit kültür testinde stimülasyon indeksi1 olan hastaların %85,7’sinde (p=0,015) graft versus host hastalığı görülmüştür. SONUÇ: Modifiye mikst lenfosit kültür, testin duyarlılığını arttırmıştır ve pozitif sonuçlar ile transplantasyondan sonra graft versus host hastalığının gelişmesi arasındaki ilişki anlamlı bulunmuştur.

The calcineurin inhibitors (CNIs) [cyclosporin A (CsA) and tacrolimus (Tac)] are currently the most widely prescribed drugs for maintenance of immunosuppression after renal transplantation. These immunosuppressants are associated with side effects such as hyperlipidemia. We evaluated the differential effects of different CNIs on serum lipid parameters in renal transplant patients. Moreover, the aim of this study is to investigate the relationships between doses and blood levels of CNIs, and blood levels of CNIs and lipid parameters retrospectively. Two groups of 98 non-diabetic renal transplant patients, each treated with different CNIs, were studied: group A (n = 50, mean age: 31 ± 10 years), CsA, mycophenolate mofetil/azathioprin, steroid; group B (I = 48, mean age: 34 ± 12 years), Tac, mycophenolate mofetil/azathioprin, steroid. In renal transplant patients, CNIs blood levels and doses were examined at 1, 3, 6, 9, and 12 months after transplantation. Biochemical laboratory parameters including plasma lipids [total-cholesterol (CHOL), low-density lipoprotein (LDL)–CHOL, high-density lipoprotein (HDL)–CHOL, and triglycerides (TG)], CNI levels and doses were examined at 1, 3, 6, 9, and 12 months after transplantation. None of the patients received anti-lipidemic drugs during the study period. Blood levels of CNIs were detectable in all whole-blood samples by Cloned- Enzyme-Donor Immunoassay (CEDIA). The relationship between CNIs blood levels and CHOL, (LDL)–CHOL, HDL–CHOL, TG were evaluated. The mean serum CHOL levels and LDL–CHOL levels of patients in group A were found significantly higher than the patients in group B during the 12 month of follow up (p 0.005). In group A the daily dose of CsA was significantly correlated with the mean blood levels of CsA at the 1st and 3rd months (r = 0.387, p = 0.005; r = 0.386, p = 0.006), respectively. In group A, the daily dose of CsA was significantly correlated with the mean serum TG levels during the 12 month of follow up (r = 0.420, p = 0.003). In group B, the daily dose of Tac was significantly correlated with the mean blood level of Tac (r = 0.335, p = 0.020) at the 1st month. No correlation was found between mean Tac blood levels and lipid parameters during the 12-month of follow up (p > 0.05). Significant positive correlation was observed between the CsA blood levels and LDL–CHOL levels (r = 0.338, p = 0.027) at the 3rd month. In the renal transplant patients with well functioning grafts, CsA therapy is associated with increased CHOL and LDL–CHOL ratio which represents an increased atherogenic risk tended to be associated with CsA. Serum LDL–CHOL levels may be effected by blood CsA levels.

Long-term use of Cyclosporin A (CsA) and Tacrolimus is known to yield serious untoward side effects including nephrotoxicity, neurotoxicity, and malignant tumor formation. Sister chromatid exchange (SCE) is used to assess the genotoxic potential of various agents. A total of 37 postrenal transplant patients receiving either CsA (n = 20) or Tacrolimus (n = 17) were included in this study. The genotoxic effects of CsA and Tacrolimus were assessed by determination of SCE frequency. In patients receiving CsA, SCE frequency was increased significantly compared to that in the control group (p = 0.001), whereas Tacrolimus did not yield such a significant change (p = 0.801). SCE frequency was not correlated with drug dosage (p > 0.05). Our results indicate that the use of CsA, but not Tacrolimus 506, is associated with an increased genotoxic effect in postrenal transplant patients.

Graft Versus Host Disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (SCT). The MLC assay has been generally accepted as a standard test for determining HLA-D region compatibility. In this study, the MLC test has been carried out on the related recipient-donor couple who were prepared for allogeneic SCT and were found to be matched for HLA-A, -B, -Cw, DR, DQ but not for -DP. The result of the MLC test was positive. We observed that HLA-DP mismatch was responsible for the increased proliferation values in MLC test. Graft Versus Host Hastalığı (GVHH) allojeneik kök hücre nakli (KHN) seyrinde halen önemli bir morbidite ve mortalite nedenidir. Mikst lenfosit kültür (MLC-Karışık Lenfosit Kültür) testi, genellikle HLA- D bölge uyumunu saptayan standart bir test olarak kabul edilir. Bu çalışmada allojeneik KHN'ne hazırlanan ve HLA-A, -B, -Cw, -DR, -DQ lokusları uyumlu ve -DP lokusu uyumsuz olan akraba hasta -verici çiftine MLC testi yapılmıştır. Test sonucu pozitif olarak saptanmış ve HLA-DP farklılığının MLC testindeki proliferasyon değerlerindeki artışlardan sorumlu olduğu gözlemlenmiştir., Graft Versus Host Hastalığı (GVHH) allojeneik kök hücre nakli (KHN) seyrinde halen önemli bir morbidite ve mortalite nedenidir. Mikst lenfosit kültür (MLC-Karışık Lenfosit Kültür) testi, genellikle HLA- D bölge uyumunu saptayan standart bir test olarak kabul edilir. Bu çalışmada allojeneik KHN'ne hazırlanan ve HLA-A, -B, -Cw, -DR, -DQ lokusları uyumlu ve -DP lokusu uyumsuz olan akraba hasta-verici çiftine MLC testi yapılmıştır. Test sonucu pozitif olarak saptanmış ve HLA-DP farklılığının MLC testindeki proliferasyon değerlerindeki artışlardan sorumlu olduğu gözlemlenmiştir.

Cytokines are essential for the control of the immune response as most of the immunosuppressive drugs target cytokine production or their action. The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are immunosuppressive drugs widely used after renal transplantation to prevent allograft rejection. They are characterized by large interindividual variability in their pharmacokinetics; therefore, monitoring their blood concentrations is important to predict their optimal dosage following transplantation. Calcineurin inhibitors inhibit the phosphatase activity of calcineurin, thereby suppressing the production of other cytokines such as transforming growth factor (TGF-β), tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-2, and IL-4. The aim of this study was to investigate the relationship between polymorphisms of cytokines and blood concentrations of CNIs in renal transplant patients. The study included 53 CsA-treated renal transplant patients and 37 tacrolimus-treated renal transplant patients. Cytokine polymorphisms were analysed using polymerase chain reaction (PCR) sequence-specific primers with the cytokine CTS-PCR-sequence-specific primers Tray Kit; University of Heidelberg. Blood concentrations of CNIs were determined with Cloned Enzyme Donor Immunoassay (CEDIA) method. Patients with TC genotype of TGF-β at codon 10 had lower CsA blood concentrations than the TT and CC genotypes (P = 0.005) at 1 month in CsA treatment group. The ratio of blood concentration/dose of CsA for patients with TGF-β1-codon 10 TC genotype was lower than for patients with TT, CC genotypes, and the dose given to these patients was higher in the first month (P = 0.046). The ratio of blood concentration/dose of CsA for patients with IL-2-330 GG genotype was higher than for patients with GT, TT genotypes, and the dose given to these patients was lower at first month and sixth months (P = 0.043, P = 0.035 respectively). The tacrolimus blood concentrations were significantly higher in patients with the genotype GG of IL-2-330 (P = 0.012) at the third month. Patients who had the TC genotype TGF-β codon 10 had lower CsA blood concentrations and this group had higher acute rejection (P = 0.033). These results suggest that the genotyping for TGF-β-codon 10, IL-2-330 and IL-6-174 polymorphisms may help individualized immunosuppressive dosage regiments.

Background Living donor kidneys from spouses and children (from offspring to parents) are currently considered to be important organ sources. However, pregnancy-induced alloimmunization may provoke acute rejection episodes after kidney transplantation. being flow cytometry cross-match (FCXM) we studied donor-specific antibodies (DSAs) in the sera of recipients planned for living kidney transplantation from their spouse or children. When the FCXM was positive, we confirmed the existence of anti-human leukocyte antigen (HLA) antibodies using flow cytometry panel-reactive antibody (flow-PRA). Patients and Methods Between March 2005 and November 2010, we tested 85 pretransplantation sera from renal transplant recipients for DSAs. The recipients included 37 wives (group I) and 48 husbands (group II). FCXM-positive sera were tested using a flow-PRA screening method using HLA class I and class II antigen-coated beads. The mean recipient age was 48.1 ± 9.8 (range, 28–69) years and the mean donor age was 45.1 ± 11.1 (range, 23–69 years). Results Among group I were 18 (48.6%) FCXM-positive cross-matches; for group II, 5 (10.4%) cases ( P = .001). Sensitized patients were 37.9% FCXM-positive, whereas nonsensitized patients were 3.7% positive ( P = .001). FCXM-positive patients were re-evaluated for anti-HLA antibodies using flow-PRA. Seventeen of 18 group I tests (94.4%) were FCXM-positive, whereas 3 of 5 (60%) were positive among group II. Conclusions We concluded that flow cytometry–based cross-match and PRA techniques can be used to detect anti-HLA antibodies using spousal or children donors for kidney transplantation.

Aim. Anti-donor antibodies, denoted as "panel-reactive antibodies" (PRAs), are one of the most important factors influencing graft survival after renal transplantation. PRA is generally analyzed with enzyme-linked immunosorbent assay or flow cytometry (FC), which identify the HLA antigen specific for the preformed antibody. Patients and methods. We tested 66 patients for FC crossmatch (FCXM) when they were called for cadaveric renal transplantation. Thirty of 66 patients were FCXM-positive; 36 were FCXM-negative. Among the FCXM positive crossmatches, 21 were T- and B-cell positive; seven B positive; and two T positive. The HLA antibodies in the sera of FCXM-positive patients were reanalyzed using flow-PRA. Results. We detected HLA antibodies in 28/66 sera with flow PRA. The sera of 16/21 T-/B-, FCXM-positive patients contained both class I and II anti-HLA antibodies, five had only class I anti-HLA antibodies. One out of seven B-cell FCXM-positive patients had class I and class II anti-HLA antibodies, three, class I and 1 class II anti-HLA antibodies; the other two were negative. Class I and class II HLA antibodies were observed in two T-cell FCXM-positive patients. Four of 36 patients who were FCXM-negative were flow PRA positive: one had both class I and class II HLA antibodies and three, only class I HLA antibody. The comparison of FCXM and flow PRA results was significant (P = .001). Conclusion. FCXM results may be confirmed by flow PRA tests, an important method to differentiate HLA versus non-HLA antibodies.

Amac: Mikofenolik asit ’ in (MPA) farmakokinetiginde bireyler arasinda farkliliklar vardir. MPA oncelikle uridin difosfat-glukuronosiltransferazlar (UGT) tarafindan metabolize olur. UGT2B7, MPA glukuronidasyonu icin onemli bir UGT ’ dir. Calismanin amaci, Turk bobrek nakilli hastalarda UGT2B7 His268Tyr (802C>T) polimorfizmlerinde MPA farmakokinetigini incelemektir. Gerec ve Yontem: Calismaya renal transplant yapilmis, 65 hasta dahil edildi. UGT2B7 His268Tyr (802C>T) genotiplemesi PCR-RFLP kullanilarak yapildi. MPA konsantrasyonlari Klonlanmis Enzim Donor Immunoassay (CEDIA) ile belirlendi. Tum hastalar calisma suresi boyunca akut rejeksiyon ve greft fonksiyonu acisindan izlendi. Bulgular: Hastalar arasinda UGT2B7 (802C>T) CC, CT ve TT genotip frekanslari sirasiyla 24 (%36,9), 36 (%55,4) ve 5 (%7,7) idi. Ucuncu ve altinci aylarda MPA duzeyleri UGT2B7 (802C>T) TT tasiyicilarinda CT ve CC tasiyanlara gore sirasiyla istatistiksel olarak anlamli derecede yuksek bulundu (p=0,038, p=0,021). MPA ’ nin doz/kan konsantrasyonu orani nakil sonrasi altinci ayda TT genotipi tasiyanlarda CC ve CT genotipi tasiyanlara gore daha yuksekti (p=0,042). TT genotipi tasiyan bireyler sirasiyla CC ve CT genotiplerine kiyasla ucuncu ve altinci ayda dusuk doz gereksinimleri gostermislerdir (p=0,109, p=0,238). Ayrica UGT2B7 (802C>T) polimorfizmi ile akut rejeksiyon arasinda bir iliski bulunmamistir (p>0,05). Sonuc: Bizim sonuclarimiz, bobrek nakilli hastalarda UGT2B7 (802C>T) polimorfizmi ile MPA farmakokinetigi arasinda bir korelasyon oldugunu gostermistir. UGT2B7 polimorfizminin saptanmasi, en uygun MPA kan konsantrasyonlari hedefi belirlenmesine yardimci olabilir.