Vural Taner Yilmaz

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

Abstract 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.

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

ABSTRACT 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.

Outcomes of Renal Transplantation in Patients With Alport Syndrome.

AIM We evaluated the outcomes of patients who underwent renal transplantation (Rtx) due to end-stage renal disease (ESRD) related to Alport syndrome in our study. MATERIALS AND METHODS Twenty-five patients (female/male: 9 [36%]/16 [64%]) who underwent Rtx at our center between 2002 and 2014 were enrolled in the study. Mean ages of patients and donors (cadaveric/living: 8 [32%]/17 [68%]) were 28.2 ± 11.6 and 42.3 ± 15.8 years, respectively. As immunosuppressive therapy, tacrolimus plus mycophenolic acid were used for 17 (68%) patients and cyclosporin plus mycophenolic acid were used for 8 (32%) patients where induction therapy was basiliximab 20 mg (day 0 and 4) for 11 (44%) patients and anti-thymocyte globulin for 8 (32%) patients. Acute rejection was diagnosed using biopsy and evaluated with Banff classification. Analyses were performed by using SPSS 20.0 software with outcomes of mean 75.4 ± 31.4 months follow-up. Patient and graft survival were measured by using Kaplan-Meier survival curve and compared by using log-rank test. RESULTS Graft survival rate was 89%, patient survival rate was 92.9%, and acute rejection rate was 12% (3 cases; 1 was cellular and 2 were antibody-mediated). Delayed graft function was observed in 4 (16%) cases, 1 patient (4%) had BK virus nephropathy and 2 (8%) patients required hemodialysis and had cytomegalovirus infection. At the last follow-up, mean serum creatinine level was 1.57 ± 1.23 mg/dL, spot urine protein creatinine ratio was 0.13 (0.04-1.84), and glomerular filtration rate was 71.7 ± 34.9 mL/min. CONCLUSION Rtx is an effective and successful treatment modality for ESRD cases related to Alport syndrome.

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.

Quantitative analysis of BKV-specific CD4+ T cells before and after kidney transplantation.

BACKGROUND BK virus (BKV) is the main infectious cause of renal allograft dysfunction. Although recent studies showed an inverse correlation between BKV-specific T-cell responses and viral load after transplantation, the importance of pre-transplant response in the process of virus reactivation has only been studied once. In this study, we aimed to determine whether pre-transplant CD4+ T-cell response can be used for prediction of BKV reactivation and BKV nephropathy (BKVN), by a method that can practically be used in routine patient monitoring. METHODS BKV-specific CD4+ T-cell responses of 31 kidney recipients (all from live donors) were measured by an IFN-γ-enzyme-linked-immunospot (ELISPOT) method using mixture of peptides, at day 0 and +1, +3, and +6 months posttransplant. Additionally, seven other reactivation patients as another group were also analyzed. BKV viral loads in plasma were measured by real-time polymerase chain reaction (PCR). Responses of 10 healthy people were also included as controls in the analysis. RESULTS All but one patient and all of the controls had detectable CD4+ T-cell responses. Reactivation occurred in 8 out of 31 patients. There was no significant association between pretransplant BKV-specific CD4+ T-cell responses and BKV reactivation and between BKV DNA levels and CD4+ T-cell responses. In the additional group consisting of reactivation patients, four patients who had BKVN showed negative correlation between BKV-DNA levels and BKV-specific CD4+ T-cell responses (p<0.05). One patient who developed BKVN, however, was not able to mount a similar CD4+ T-cell response to viral reactivation despite immunosuppressive reduction. CONCLUSION Even though our cohort is small, our results may suggest that pre-transplant measurement of BKV specific CD4+ T-cell response may not be necessary, and that post-transplant monitoring, particularly during reactivation, may be more helpful in the management of the infection.

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.

New-Onset Diabetes Mellitus Associated with Sirolimus Use in Renal Transplant Recipients.

New-onset diabetes after transplantation and impaired glucose tolerance are very common in renal transplant patients. New-onset diabetes after transplantation (NODAT) is associated with increased cardiovascular morbidity and mortality, reduced graft and patient survival. Several risk factors for NODAT have been identified: age, obesity, family history of diabetes mellitus and HCV infection. In addition, steroid and calcineurin inhibitors also contribute to the development of NODAT. Sirolimus causes immunosuppressive effects by inhibiting mammalian target of rapamycin (mTOR), and has well known side effects. The effects of sirolimus on glucose metabolism and contribution to NODAT development are not clearly known. In this report, we presented five RTX patients who developed NODAT under the treatment of sirolimus.

The association of serum-free light-chain levels with markers of renal function

Abstract Background: The kidney is often affected in plasma cell dyscrasias, usually due to the effects of nephrotoxic monoclonal-free light chains. Renal failure due to a monoclonal gammopathy may be detected by the highly sensitive serum-free light-chain (sFLC) ratio yet missed by electrophoretic assays. The aim of this study was to assess sFLC levels in relation to markers of renal function. Methods: Five-hundred thirteen patients were included in this study. sFLC levels were measured by Freelite® (The Binding Site Group Ltd, Birmingham, UK) assay using the BNII nephelometer (Siemens Diagnostics, Germany). Kappa/lambda (κ/λ) sFLC ratio was calculated. Serum creatinine levels were analyzed by modified Jaffe method in Cobas 8000 analyser. GFR was estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Patients were assigned to two groups depending on their eGFR values: ≤60 mL/min/1.73 m2 (Group 1, n = 103) and >60 mL/min/1.73 m2 (Group 2, n = 410). Data were expressed as median and min–max. All the statistical analyses were done with SPSS version 20.0 and a significance level of 0.05 was considered. Results: Serum κ-FLC median value was 36.4 (5.62–16,000) mg/L, serum λ-FLC was 21.7 (4.91–8770) mg/L, κ/λ sFLC ratio was 1.33 (0.01–3258) and serum creatinine was 1.56 (0.63–7.21) mg/dL in Group 1. Both λ sFLC and κ/λ sFLC ratios were correlated with eGFR (r = −0.318, r = 0.198, p < 0.05, respectively). We did not find any significant correlation between κ/λ sFLC ratio and eGFR in Group 2. Conclusions: We examined the association between sFLC concentrations and renal function. Our preliminary findings suggest that serum λ-FLC might be considered as a useful marker for predicting renal function. Prospective studies are needed to clarify the usefulness of these parameters for identifying renal failure due to a monoclonal gammopathy.

Assessment of Long-Term Outcomes in Hbs Ag-Negative Renal Transplant Recipients Transplanted from Hbs Ag-Positive Donors

BACKGROUND The aim of this study was to evaluate the long-term outcomes of renal transplantation from Hbs Ag-positive donors to Hbs Ag-negative recipients. MATERIAL AND METHODS A total of 78 patients who underwent renal transplantation in our clinic between January 2006 and May 2014 were included in the study. Patients were divided into 2 groups: Group 1: Donor Hbs Ag (+) (n=26, Hbs Ab (-), Hbe Ag (-), Hbe Ab (+), Hbc Ig total (+) and HBV DNA (+), male/female (M/F): 16 (61.5%)/10 (38.5%), and Group 2: Donor Hbs Ag (-) (n=52, M/F: 41 (78.8%)/11 (21.2%). Hbs Ab levels were similar in recipients in both groups. Data were collected retrospectively. Analyses were performed by using SPSS 20.0 software, and patient and graft survival were measured by using Kaplan-Meier survival curve and compared by using the log-rank test. RESULTS Demographic data were similar in the 2 groups. The rate of acute Hepatitis B infection was significantly higher in Group 1 than in Group 2 [n=3 (11.5%) vs. n=0 (0%), respectively, p=0.012]. Acute hepatitis B attacks were detected in vaccinated patients. Graft survival rates (groups 1 and 2, respectively; at 1st, 3rd, 5th and 8th years: 95% vs. 96%, 95% vs. 94%, 85% vs. 88%, 85% vs. 82%, p=0.970) and patient survival rates (p=0.098), acute rejection rates (p=0.725), delayed graft function, chronic allograft dysfunction, new-onset diabetes after transplantation (NODAT), cytomegalovirus infection, and the need for postoperative dialysis and plasmapheresis were similar between groups. CONCLUSIONS Our study revealed that the risk of developing acute hepatitis B was higher in patients renally transplanted from Hbs Ag (+) donors, but the other clinical outcomes were similar between groups.

Acute renal failure due to uterine prolapse: a case report

Abstract Herein, we present a successfully treated case with acute renal failure due to ureteral obstruction caused by total uterine prolapsed. A 55-year-old female patient presented to our hospital with the complaints of protrusion of the uterus for the last 3 months, pollakiuria, nocturia, decreased urine volume, and swelling of her body for the last week, and as well as impaired general status with shortness of breath for the last several days. Her physical examination revealed a blood pressure of 140/90 mmHg, pulse rate of 80 beats/min, body temperature of 37.8 °C, as well as uterine prolapse with infection and erosion on the surface of the uterus, crepitating rales in the basal segments of both lungs, and pretibial edema. Results of laboratory analyses were as follows: BUN = 70 mg/dL, Cr = 6.5 mg/dL, CRP = 8.7 mg/dL, and leukocyte = 12,000/mm3. Blood gas analysis revealed a pH of 7.35 and bicarbonate level of 14 mmol/L. Data obtained from ultrasonography, DTPA scintigraphy, and abdominal CT, which were performed assuming that the patient had post-renal renal failure due to the compression by uterus, supported this assumption. Bilateral nephrostomy catheters were inserted and appropriate fluid-electrolyte therapy for volume status and antibiotherapy were commenced. Renal functions returned to normal levels on the 4th day of therapy and her complaints disappeared. The patient underwent total abdominal hysterectomy and was monitored in terms of renal functions and diuresis. The present case was presented due to its importance for being a quite rare case who dramatically responded to accurate intervention performed in time.