Evaluation of Overall Survival and Disease-Free Survival in Patients Receiving Liver Transplantation for Hepatocellular Carcinoma and Comparison of Living Versus Deceased Donor Liver Transplants: Results of 15 Years of Experience.

OBJECTIVE: Research comparing patients who received liver transplantation (LT) for hepatocellular carcinoma (HCC) has produced varying outcomes regarding survival and disease-free survival. The objective of this study is to determine the factors that influence the disease-free and overall survivals of those who have undergone LT for HCC and to compare the outcomes of living versus deceased donor liver transplants. MATERIALS AND METHODS: We retrospectively analyzed data on patients aged 18 and above who received LT for HCC from 2006 to 2022. Patients with a follow-up period of less than 6 months and who did not meet the University of California San Francisco criteria were excluded. The data from 58 patients were analyzed. We split the patients into living donor liver transplantation (LDLT) (group 1) and deceased donor liver transplantation (DDLT) (group 2). RESULTS: The mean age was 56 ± 8.1 years. There were 49 males and 9 females. The median of the alphafetoprotein (AFP) level and model for end-stage liver disease score was 10.1 ng/mL and 11, respectively. The 1-, 3-, 5-, and 10-year disease-free survival rates were 86%, 76.5%, 76.5%, and 76.5%, respectively. The survival rates for the same periods were 94.8%, 74.9%, 70.6%, and 67.4%. The receiver operating characteristic analysis revealed that AFP > 31.8 ng/mL and a total tumor size >3.85 cm raise the likelihood of HCC recurrence post-LT. CONCLUSION: Based on the current literature, the overall survival and disease-free survival rates are influenced by factors such as AFP value, total tumor number, and total tumor diameter. In our study, the AFP value and total tumor size had an impact on the recurrence of HCC, and the survival rates were comparable on LDLT and DDLT.

Predictive Factors of BK Virus Development in Kidney Transplant Recipients and the Effect of Low-Dose Tacrolimus Plus Everolimus on Clinical Outcomes.

OBJECTIVES: This study aimed to determine the predictive factors of BK virus viremia/nephropathy in kidney transplant recipients and to evaluate the effects of low-dose tacrolimus plus everolimus. MATERIALS AND METHODS: This study included 3654 kidney transplant recipients. The patients were divided into 2 groups: group 1 were BK virus negative (n = 3525, 96.5%) and group 2 were BK virus positive (n = 129, viremia 3.5%, nephropathy 1%). Predictive factors were determined by receiver operating characteristic curve analysis and logistic regression models.We also divided and analyzed patients with BK virus viremia/nephropathy into 2 groups according to immunosuppressive changes. Group 2a had been switched to low-dose tacrolimus plus everolimus (n = 54, 41.9%), and group 2b had been switched to other immunosuppressive protocols (n = 75, 58.1%). RESULTS: We found that use of anti-T-cell lymphocyte globulin and tacrolimus, deceased donor transplant, and rejection were predictive factors for BK virus viremia/nephropathy. In addition, patients who had low-dose calcineurin inhibitor plus mammalian target of rapamycin inhibitor regimens showed a low rate of BK virus development(only 6.2% of all cases). In Group 2a, both the BK polyomavirus-associated nephropathy rate (n = 23 [42.6%] vs n = 12 [16%] in group 2b; P = .001) and viral load (DNA > 104 copies/mL) (n = 49 [90.7%] vs n = 27 [36%] in group 2b; P = .001) were increased versus group 2b. Graft function, graft survival, viral clearance, and rejection rate were similar between the groups after protocol change. CONCLUSIONS: BK virus viremia/nephropathy rate was lower in patients who received low-dose calcineurin inhibitor plus mammalian target of rapamycin inhibitor protocols; the low-dose tacrolimus plus everolimus switch protocol after BK virus was more effective and safe than other protocols.

Evaluation of the relationship between de-novo DSA development and CXCR5+PD-1+CD8+ T cells and PD-1/PD-L1 mRNA expression in kidney transplant recipients.

BACKGROUND AND AIMS: The relationship between the Follicular Cytotoxic T cell subgroup and expression levels of PD1/PD-L1 genes and the development of donor specific antibody (DSA) is unknown. In this study, we aimed to examine CD8+CXCR5+PD-1+ follicular cytotoxic T cell levels and expression levels of PD1/PD-L1 genes in peripheral blood lymphocytes in de-novo DSA positive and negative kidney transplant recipients (KTR). METHODS: In our study, expression of PD-1/ PD-L1 genes by Real-Time Quantitative PCR method and CD8+CXCR5+PD-1+ T cell expression levels by flow cytometric method were obtained from peripheral blood samples. 63 participants were included in the study (de-novo DSA positive recipients (n = 22, group 1), de-novo DSA negative recipients (n = 20, group 2) and healthy control (n = 21, group 3). All patients had negative PRA before kidney transplantation. Expression (%) levels of target cells were evaluated by flow cytometry method. IBM SPSS Statistics for Windows Version 22 and R.3.3.2 software were used to evaluate the data. RESULTS: The demographic data of the groups were similar. PD-1 mRNA expression was higher in de-novo DSA positive KTR than negative (respectively, 1.03 ± .29/.82 ± .15, p: .001). CD8+CXCR5+PD-1+ T cell expression levels were found to be higher in the de-novo DSA positive group than in the negative group and similar to the healthy group (respectively, 3.06 ± 1.98/.52 ± .40, p:.001, 3.06 ± 1.98/2.78 ± .59, p:.62). The percentage of CD8+CXCR5+PD-1+ expressing T cells was significantly lower in the HLA-Class II+ group than other groups (HLA CI/II/ I+II, respectively, 3.63 ± 2.72/1.65 ± .50/3.68 ± 1.67, p: .04). CONCLUSIONS: In our study, a significant relationship was found between DSA formation and PD-1 mRNA level and CD8+CXCR5+PD-1+ follicular cytotoxic T cell in KTR.

The Factors Affecting Mortality After Pediatric Liver Transplantation and Long-Term Survival Outcomes: A Single Center Experience.

BACKGROUND: Liver transplantation (LT) is a treatment modality in the pediatric population for several diseases like biliary atresia, metabolic liver disease, hepatoblastoma, and so on. According to the Organ Procurement and Transplantation Network, 5-year survival was reported as 85.4% to 93.5% by age after pediatric liver transplantation (PLT). This study aimed to evaluate our single-center experience of PLT by analyzing long-term results, comparing the outcomes with the literature, and identifying predictors of patient survival. METHODS: The data of 40 patients who underwent LT at <18 years of age between June 2015 and June 2021 were studied retrospectively. Recipient characteristics such as age, sex, etiology of liver disease follow-up time, postoperative vascular and biliary complications, and donor characteristics were evaluated. RESULTS: There were 20 (50%) girls and 20 (50%) boys, and the median age was 42 (IQR = 9-117) months. The most common indications of LT were biliary disorders (45%). A whole liver graft was used in 7 (17%), a right lobe graft in 9 (23%), a left lobe graft in 4 (10%), and a left lateral lobe graft in 20 (50%) of the recipients. The 1-, 3-, 5-, and 7-year survival rates were 85%, 82.1%, 82.1%, and 82.1%, respectively. The multivariate survival analysis revealed that the pediatric end-stage liver disease score, hepatic artery thrombosis, and portal vein thrombosis are associated with overall mortality. CONCLUSION: In conclusion, our long-term survival is similar to the literature, with satisfactory results. However, reducing the vascular complication rates can provide superior results on PLT.

Regulatory B Cells Profile in Kidney Transplant Recipients With Chronic-Active Antibody-Mediated Rejection.

This study aims to reveal the relationship between regulatory B cell (Breg) subsets and chronic-active antibody-mediated rejection (c-aABMR) in renal transplant recipients. Our study involved 3 groups of participants: renal transplant recipients with biopsy-proven c-aABMR as the chronic rejection group (c-aABMR, n = 23), recipients with stable graft functions as the patient control group (PC; n = 11), and healthy volunteers (HV; n = 11). Breg subsets, immature/transitional B cells, plasmablastic cells, B10 cells, and BR1 cells were isolated from venous blood samples by flow cytometry. The median values of Breg frequencies in the total lymphocyte population were analyzed. There were no significant differences between the study groups for immature and/or transitional B cell frequencies. Plasmablastic cell frequencies of the c-aABMR group (7.80 [2.10-27.40]) and the PC group (6.00 [1.80-55.50]) were similar, but both of these values were significantly higher than the HVs' (3.40 [1.20-8.50]), (respectively, P = .005 and P = .039). B10 cell frequencies were also similar, comparing the c-aABMR (4.20 [0.10-7.40]) and the PC groups (4.10 [0.10-5.90]), whereas the HVs (5.90 [2.90-8.50]) had the highest B10 cell frequency with an only statistical significance against the PC group (respectively, P = .09 and P = .028). The c-aABMR and the PC groups were similar regarding BR1 cell frequencies. However, the HV group significantly had the highest frequency of BR1 cells (5.50 [2.80-10.80]) than the other groups (P < .001 for both). We demonstrated that frequencies of B10 and BR1 cells were higher in HVs than in transplant recipients, regardless of rejection state. However, there was no significant relation between Breg frequencies and the c-aABMR state.

Impact of older age on the long-term survival in living-donor liver transplantation: A propensity score matching analysis.

BACKGROUND: Prevalence of the end-stage liver disease in the elderly patients indicating a liver transplantation (LT) has been increasing. There is no universally accepted upper age limit for LT candidates but the functional status of older patients is important in pre-LT evaluation. This study aimed to examine the impact of older age on survival after living donor liver transplantation (LDLT). METHOD: A total of 171 LDLT recipients were assessed in two groups: age ≥65 and < 65. To eliminate selection bias propensity score matching (PSM) was performed, and 56 of 171 recipients were included in this study. RESULTS: There were 20 recipients in the older group and 36 in the younger. The 1-, 3-, and 5-year survival rates were 65.0%, 60.0%, and 60.0% in group 1; 88.9%, 84.7%, and 71.4% in group 2, respectively. The 1-year survival was significantly lower in the older recipients; however, overall survival rates were similar between the groups. Of the 56 recipients, 15 (27%) deaths were observed in overall, and 11 (20%) in 1-year follow-up. The univariate regression analysis after PSM revealed that MELD score affected 1- year survival and the multivariate analysis revealed that age ≥65 years and MELD score were the predictors of 1-year survival. CONCLUSION: At first sight, before PSM, survival appeared to be worse for older recipients. However, we have shown that there were confounding effects of clinical variables in the preliminary evaluation. After the elimination of this bias with PSM, This study highlights that older recipients have similar outcomes as youngers in LDLT for long-term survival.

A UFLC-MS/MS Method for the Simultaneous Analysis of Urinary Podocin and Podocalyxin in Patients with Nephrotic Syndrome.

OBJECTIVE: To create an efficient and robust mass spectrometric method for the simultaneous quantitation of podocin and podocalyxin in urine samples and to evaluate urinary podocin and podocalyxin levels in patients with nephrotic syndrome (NS). METHODS: A mass spectrometric method was generated for the measurement of tryptic peptides in urine sediment. Separation of peptides was achieved via liquid chromatography, and mass spectrometric analyses were conducted by electrospray ionization triple-quadrupole mass spectrometry in the multiple reaction monitoring mode. RESULTS: Intra- and interassay precision values were below 12% and accuracies ranged from 87% to 111% for both of peptides. The validated method was successfully applied to detect these peptides in patients with NS. Urine podocin and podocalyxin levels were significantly higher in patients with NS compared to healthy controls. CONCLUSIONS: This proposed mass spectrometric method provides technological evidence that will benefit the clinical field in the early diagnosis and follow-up of NS.

Safety and Threshold Analysis of Preoperative Platelets in Right Lobe Living Donors for Liver Transplantation.

BACKGROUND: Low perioperative platelet count is a powerful independent risk factor for posthepatectomy liver failure. Usually, categorical effect of thrombocytopenia was taken into account; upper thresholds were not studied in depth, exclusively in living liver donors. METHODS: Living liver donors who underwent right hepatectomy were included. Preoperative characteristics of donors were identified and examined to predict posthepatectomy liver failure. To eliminate selection bias, one-to-one propensity score matching was performed. RESULTS: There were a total of 139 living donors and 40 (29%) donors developed posthepatectomy liver failure in the aftermath of the operation. Remnant liver volume ratio and preoperative platelet count were identified as adjustable independent risk factors (OR: 0.89 and 0.99, 95% CI: 0.79-0.99 and 0.98-0.99, respectively). After propensity score matching, odds ratio of preoperative platelet count was 0.99 (95% CI: 0.98-1.00). CONCLUSIONS: Preoperative platelet count, in addition to remnant liver volume ratio, can be used as a surrogate marker to predict the risk of posthepatectomy liver failure in living liver right lobe donors. Probability curves figured out from logistic regression analysis, in this regard, provided an explicit perspective of platelets having a decisive role on liver donor safety. Thus, remaining in safer remnant liver volume ratio limits with respect to preoperative platelet count should be addressed in safe donor selection strategies.

Association Between Graft Function and Urine CXCL10 and Acylcarnitines Levels in Kidney Transplant Recipients.

OBJECTIVE: To evaluate post-transplantation graft functions noninvasively by using urine C-X-C motif chemokine 10 (CXCL10) and metabolome analysis. METHODS: The 65 living-donor kidney-transplant recipients in our cohort underwent renal biopsy to investigate possible graft dysfunction. The patients were divided into 2 groups, according to pathology reports: chronic allograft dysfunction (CAD; n = 18) and antibody-mediated/humoral allograft rejection (AMR; n = 16). The control group was composed of renal transplant recipients with stable health (n = 33). We performed serum creatinine, blood urea nitrogen (BUN), cystatin C, urine protein, CXCL10, and metabolome analyses on specimens from the patients. RESULTS: BUN, creatinine, cystatin C, urine protein, leucine + isoleucine, citrulline, and free/acetyl/propionyl carnitine levels were significantly higher in patients with CAD and AMR, compared with the control individuals. CXCL10 levels were significantly elevated in patients with AMR, compared with patients with CAD and controls. CXCL10 (AUC = 0.771) and cystatin C (AUC = 0.746) were significantly higher in the AMR group, compared with the CAD group (P<.02). CONCLUSIONS: CXCL10 and metabolome analyzes are useful for evaluation of graft functions. Also, CXCL10 might be useful as a supplementary noninvasive screening test for diagnosis of allograft rejection.

The use of anti-interleukin-1 agents and tumor necrosis factor-alpha inhibitors in renal transplant recipients.

OBJECTIVES: The aim of this study was to investigate the efficacy and safety of anti-interleukin-1 (anti-IL-1) agents and tumor necrosis factor-alpha (TNF-α) inhibitors in renal transplant patients. PATIENTS AND METHODS: Between February 2014 and February 2020, data of 12 renal transplant recipients (9 males, 3 females; median age: 51 years; range, 19 to 70 years) who received anti-IL-1 agents or TNF-α inhibitors for inflammatory diseases in the post-transplant time period and were followed in a single transplant center (n=12) were retrospectively analyzed. A total of 46 cases were reported in the literature, before the data were collected. The overall outcomes of all cases were analyzed in this study. RESULTS: Thirty-seven patients received anti-IL-1 agents in the post-transplant period. The main indications for anti-IL-1 agents were familial Mediterranean fever (FMF) and amyloidosis (75.7%). The continuation rate of colchicine treatment in patients with FMF was 85.7%. Anti-IL-1 agents prevented attacks completely in 89.3% of FMF patients. The number of cases used TNF-α inhibitors among renal transplant patients was lower (n=21). The TNF-α inhibitors were used mainly for inflammatory bowel diseases (57.1%) and ankylosing spondylitis (33.3%) and suppressed the disease activity in most of the patients with inflammatory diseases (72.7%). Death (n=3) and malignancies (n=3) were reported in patients who received TNF-α inhibitors, but not in patients who received anti-IL-1. The renal outcomes and graft survival rates were satisfactory in patients who received both anti-IL-1 agents and TNF-α inhibitors. CONCLUSION: Our results support that anti-IL-1 agents can be used effectively and safely in renal transplant patients.

Serum Levels of S100ß, Neuron-Specific Enolase, Glial Fibrillary Acidic Protein in Kidney Transplant Recipients and Donors: A Prospective Cohort Study.

BACKGROUND: The aim of this study was to evaluate changes in serum levels of S100ß, neuron-specific enolase, glial fibrillary acidic protein in living donors and recipients after kidney transplantation. METHODS: We enrolled 56 patients into the study. Of these, 27 underwent donor nephrectomy (group D), and the remaining 29 underwent kidney transplantation (recipient, group R). Neuromarkers were measured in samples obtained before the procedure, on postoperative day 7, and at 1 month postoperatively. RESULTS: Postoperative kidney functions were impaired in patients who underwent living donor nephrectomy compared with their preoperative levels (P < .001), although no significant difference was observed in their neuromarkers. The postoperative delirium rating scale was also impaired after living donor nephrectomy compared with preoperative levels (P < .05). Postoperative kidney functions were improved (P < .001), and a progressive decrease in neuromarker levels (P < .05) was observed in kidney transplant recipients compared with their preoperative levels. Linear regression analysis showed a significant correlation between neuron-specific enolase, glial fibrillary acidic protein levels and kidney functions in recipients. CONCLUSION: The present study demonstrated that neuron-specific enolase and glial fibrillary acidic protein levels decrease in kidney transplant recipients and do not change in donors. This result indicated that there is no evidence of neurotoxicity in either recipients and donors in kidney transplantation.

A Single-Center Experience in Portal Flow Augmentation in Liver Transplantation With Prior Large Spontaneous Splenorenal Shunt.

Large portosystemic shunts may cause portal steal syndrome in liver transplantation (LT). Because of the possible devastating consequences of the syndrome, the authors recommend perioperative management of these large shunts. Fourteen adult recipients who underwent portal flow augmentation, including left renal vein ligation (LRVL), renoportal anastomosis (RPA), shunt ligation (SL), and splenic vein ligation (SVL) for large spontaneous splenorenal shunt (SSRS), are included in this study, and the results were analyzed. A total of 13 patients had a large SSRS, and in 1 patient, the large shunt was placed between the superior mesenteric vein and the right renal vein. LDLT was performed in 13 patients. LRVL (n = 5), SVL (n = 6), RPA (n = 2), SL (n = 1) were performed to the patients as graft inflow augmentation. The graft-recipient weight ratios (GRWR) were less than 0.8% in 5 patients (35.7%): 2 had LRVL, and 3 had SVL. Small-for-size syndrome (SFSS) occurred only in these 2 patients with LRVL (GRWR ≤0.8%) and, splenic artery ligation was performed for graft inflow modulation. No mortality or serious complications were reported during follow-up. We consider that in patients with large SSRS and small-for-size grafts, SVL can be performed safely and with satisfactory outcomes.

Fabry Disease Prevalence in Renal Replacement Therapy in Turkey.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from lack of alpha-galactosidase A (AGALA) activity in lysosomes. OBJECTIVE: In this multicenter study, we aimed to evaluate the prevalence of FD in renal transplant (Tx) recipients in Turkey. We also screened dialysis patients as a control group. METHODS: All Tx and dialysis patients were screened regardless of the presence of a primary disease. We measured the AGALA activity in all male patients as initial analysis. Mutation analysis was performed in male patients with decreased AGALA activity and in female patients as the initial diagnostic assay. RESULTS: We screened 5,657 patients. A total of 17 mutations were identified. No significant difference was observed between the groups regarding the prevalence of patients with mutation. We found FD even in patients with presumed primary kidney diseases. Seventy-one relatives were analyzed and mutation was detected in 43 of them. We detected a patient with a new, unknown mutation (p.Cys223) in the GLA gene. CONCLUSIONS: There are important implications of the screening. First, detection of the undiagnosed patients leads to starting appropriate therapies for these patients. Second, the transmission of the disease to future generations may be prevented by prenatal screening after appropriate genetic counseling. In conclusion, we suggest screening of kidney Tx candidates for FD, regardless of etiologies of chronic kidney disease.

Consideration of difficulties and exit strategies in a case of face allotransplantation resulting in failure.

We describe the first rescue procedure in a case of total face allotransplantation. The recipient was a 54-year-old man with severe disfigurement of the entire face following an accidental gunshot injury 5 years previously. The large defect included the maxilla, mandible, and mid-face. Full face procurement was performed from a multiorgan cadaveric donor and was allotransplanted to the recipient. The post-transplant induction immunosuppressive regimen included ATG combined with tacrolimus, mycophenolate mofetil, and prednisone, while maintenance was provided by the last three of these. Although the early postoperative period was uneventful, squamous cell carcinoma developed in the upper and lower extremities in the fifth postoperative month, and post-transplant lymphoproliferative disorder (PTLD) occurred in the sixth month postoperatively. Malignancies were treated, involving both surgical and medical approaches. The patient developed opportunistic pulmonary and cerebellar aspergillosis. In order to reduce the adverse affects and metabolic and immunological load, the transplanted face was removed and replaced with a free flap. Although the early postoperative period was promising, with the transferred flap surviving totally and all vital signs and general status appearing to be improving, the patient was eventually lost due to complicated infectious and metabolic events. Although this case was unsuccessful, we suggest that the immunological and metabolic load should be reduced as soon as stable medical conditions are established in case of diagnosis of a situation involving a high rate of mortality, such as PTLD and untreatable opportunistic infections. This should include withdrawal of all immunosuppressive drugs and removal of all allotransplanted tissues.

Therapy Modalities for Antibody Mediated Rejection in Renal Transplant Patients.

INTRODUCTION: The aim of our study was to determine the effectiveness of immunoglobulin, rituximab and plasmapheresis in renal transplant patients with antibody mediated rejection (AMR). PATIENTS AND METHODS: Fourteen renal transplant patients with AMR were included in this study. The mean age of the patients was 33.9 ± 10.3 years and 10 (71.4%) of them were male. Lymphocyte cross match was negative for all patients and 10 (71.4%) of them were living donor transplants. Six patients were administered tacrolimus, three patients cyclosporine, two patients everolimus, and three patients sirolimus for immunosuppression. The patients with AMR were administered IVIG, rituximab and plasmapheresis. RESULTS: Patient survival rate was 100%, graft survival rate after AMR was 50% in the first year and 33% in the 2nd and third years. AMR developed 31.9 ± 25.9 months after transplantation. Seven (50%) patients lost their grafts. Delayed graft function was observed in 28.6%, chronic allograft dysfunction in 78.5%, diabetes after transplantation in 14.3%, and cytomegalovirus infection in 7.1% of the patients. At the last follow-up, the mean blood creatinine was 3.1 ± 1.4, the mean proteinuria was 2300 (1300-3300) mg/day and the mean GFR was 34.5 ± 17.6 ml/min. C4d was positive in peritubullar capillaries in all patients, while neutrophil accumulation in peritubular and glomerular capillaries was observed in 8 patients. Chronic allograft vasculopathy was observed in 12 patients. CONCLUSION: AMR leads to progressive loss of renal function and has low graft survival. More effective treatment alternatives are needed for this clinical issue.

Association of interleukin 18-607A/C and -137C/G polymorphisms with oxidative stress in renal transplant recipients.

Objectives IL-18 mediates various inflammatory and oxidative responses including renal injury, fibrosis, and graft rejection. It has been reported that the promoter -607 and -137 polymorphisms of IL-18 influence the level of IL-18. This prospective observational study investigated the association between oxidative stress with IL-18-607 and -137 polymorphisms in renal transplant recipients. Patients and methods This study included 75 renal transplant recipients (28 female, 47 male) from living-related donors. Blood samples were collected immediately before and after transplantation at day 7 and month 1. Serum IL-18, creatinine, cystatin C, CRP, and oxidative stress markers (TOS, TAC) were measured. The Oxidative Stress Index (OSI) was calculated. Polymorphisms of the promoter region of the IL-18 gene, IL18-607A/C, and -137C/G were determined by analysis of a "real-time PCR/Melting curve". Results Serum creatinine, cystatin C, CRP, IL-18, TOS, and OSI levels significantly decreased after transplantation. Post-transplant levels of serum TAC and estimated GFR demonstrated consistent significant increases. Serum IL-18 levels were significantly higher in patients with IL-18-137 GG and IL-18-607 CC genotypes before transplantation. Conclusion Our results indicate that the IL-18-137 GG and -607 CC genotypes contribute to higher IL-18 levels; however, the influence of these polymorphisms on oxidative stress has not been observed.

Nebivolol Ameliorates Hepatic Ischemia/Reperfusion Injury on Liver But Not on Distant Organs.

INTRODUCTION: Hepatic ischemia/reperfusion injury may occur after large tumor resection and liver transplantation procedures. Nitric oxide was shown to have protective effects on ischemia/reperfusion injury. Nebivolol is a compound that has been reported to improve nitric oxide release. We evaluated the effects of nebivolol in a rat liver ischemia/reperfusion model. METHODS: A total of 40 rats were randomly divided into four groups (n = 10 each). Group I underwent only laparotomy, Group II was administered nebivolol and then underwent laparotomy, Group III underwent laparotomy and hepatic ischemia/reperfusion, and Group IV was administered nebivolol and then underwent laparotomy and hepatic ischemia/reperfusion. Serum AST, ALT, urea, and creatinine levels, and TAS and TOS levels of liver, lung, and kidney tissues were determined. Histopathological determination was also performed. RESULTS: Nebivolol significantly reduced liver function tests in group IV, but it did not improve renal functions. Oxidative stress and abnormal histopathological findings were found to be reduced in liver tissue in group IV. Although the oxidative stress was increased after hepatic ischemia/reperfusion, nebivolol could not reduce the oxidative stress in kidney tissue. There were no significant differences between group III and group IV in terms of the histopathological changes in kidney tissue. There were no significant differences in lung tissue between the groups. CONCLUSIONS: The results of this study suggest that nebivolol has protective effects on liver but not on distant organs in a hepatic ischemia/reperfusion injury model. These experimental findings indicate that nebivolol may be useful in the treatment of hepatic ischemia/reperfusion injury.

Significant Association between Serum Levels of Von Willebrand Factor (vWF) Antigen with Stages of Cirrhosis.

OBJECTIVE: Von Willebrand factor (vWF) is a mediator that increases endotoxemic medium like in cirrhosis. In this study we evaluated the association of serum VWF antigen (Ag) level with the stage of cirrhosis (according to Child-Pugh classification). MATERIALS AND METHODS: We included 82 cirrhotic patients (Female/Male (F/M): 26/56) and 86 healthy subjects (F/M: 44/42) in the study. Ages of the both groups of patients were not different (P= 0.095). We excluded possible other reasons that may cause VWF level increase. Diagnosis of cirrhosis was made on the basis of biopsy in 7 patients and with clinical and laboratory parameters in 75 patients. VWF Ag level was determined by immunoturbidimetric test. The stage of cirrhosis was defined with Child-Pugh classification. Data were analysed by using Statistical Package for the Social Sciences (SPSS) 10.0 software program. RESULTS: VWF Ag level was significantly higher in cirrhotic patients compared to control group (220±90 and 87±38, P<0.001, respectively). We observed significant increase of VWF Ag level with the increasing stages of cirrhosis according to Child-Pugh score (VWF Ag level for Child A-B-C 156.4±54/215±45/284.8±93, respectively; P values for Child A-B/A-C/B-C; <0.001/<0.001/0.006, respectively). CONCLUSION: Serum VWF Ag level increases in cirrhotic patients and this is more pronounced with higher stages of cirrhosis.

Association between graft function and serum TNF-α, TNFR1 and TNFR2 levels in patients with kidney transplantation.

INTRODUCTION: This prospective observational study aimed to assess the relevance of serial postoperative serum TNF-α, TNFR1 and TNFR2 measurements for predicting graft function and acute rejection episodes (AR) after transplantation. MATERIALS AND METHODS: We studied 50 kidney transplant recipients (31 female, 19 male; mean age: 38.36 ± 12.88). Blood samples were collected immediately before and after surgery at day 7, month 1 and month 3. Serum TNF-α, TNFR1 and TNFR2 levels were measured by ELISA using a commercial kit (Invitrogen ELISA). Serum cystatin-C levels were measured by particle-enhanced immunonephelometric method. Glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease-Epidemiology (CKD-EPI) equation. Patients were assigned to their transplant outcomes in terms of acute rejection [AR(+) and AR(-)] and slow (SGF) or immediate graft function (IGF). RESULTS: Among 50 recipients, six had AR(+) and 44 had AR(-), depending on graft function: 17 had SGF and 33 had IGF. Serum creatinine, cystatin-C, TNF-α, TNFR1 and TNFR2 levels demonstrated consistent significantly decreases after transplantation while GFR values had consistent increases (p = 0.001). Pretransplant levels were not statistically different between AR(+) and AR(-) groups (TNF-α: 30.79 ± 5.96 vs. 27.95 ± 2.43 pg/mL, TNFR1: 55.96 ± 21.6 vs. 40.52 ± 7.41 ng/mL, TNFR2: 58.31 ± 8.06 vs. 50.9 ± 3.34 ng/mL, respectively) (p > 0.05). Serum TNF-α, TNFR1 and TNFR2 levels on day 7 and month 1 were also significantly higher in AR(+) group compared to AR(-) (p = 0.012, p = 0.049 for TNF-α, p = 0.001, p = 0.002 for TNFR1, p = 0.001, p = 0.002 for TNFR2). CONCLUSIONS: Our preliminary findings suggest that serum TNF-α, TNFR1 and TNFR2 levels might be considered useful markers of evaluating graft function after renal transplantation.

Chyluria and delayed graft function in early posttransplant period in a renal transplant patient.

Chyluria mostly occurs because of the leakage of lymphatic fluid into the urinary system from the lymphatic system. The patient reported here with end-stage renal disease caused by the nephrotic syndrome underwent renal transplantation from a living donor. During the early posttransplant period, her daily urine output was 300 to 400 mL, and it was chylous. The only abnormality on physical examination was pretibial edema. On renal biopsy, there was no sign of glomerular disease, acute tubular necrosis, or rejection that could have caused delayed graft function. All factors except surgery were excluded, and a lymphourinary fistula was demonstrated with lymphoscintigraphy. After 15 days, chyluria resolved and she recovered spontaneously. Normal diuresis began, and her creatinine level decreased to less than 1 mg/dL in 3 days. According to our knowledge, this is the first chyluria case secondary to surgery in the posttransplant setting.