Urinary CXCL9 and CXCL10 Levels and Acute Renal Graft Rejection.

BACKGROUND: Monitoring of chemokines, CXCL9 and CXCL10, in serum may present a non-invasive detection method for rejection. OBJECTIVE: To investigate the relationship between urinary levels of CXCL9 and CXCL10 and graft function following renal transplantation. METHODS: 75 living-related donor renal transplant recipients were studied. Urinary levels of chemokines were collected pre-operatively, on post-operative 1st day, 7th day, 1st month, 3rd month, and at the time of rejection. Chemokines levels were assayed using and enzyme-linked immunosorbent assay. RESULTS: Clinical variables were monitored. 10 (15%) patients had biopsy-proven rejection during the follow-up period. The urinary CXCL9 level in those with rejection was significantly higher than that in those with non-rejection group at the 1st day (p<0.001), 7th day (p<0.001), and at the time of rejection (p=0.002). The urinary CXCL10 level was also significantly higher in those with rejection compared with non-rejection group at 1st day (p<0.001), 7th day (p<0.001), and at the time of rejection (p=0.001). Serum creatinine level was strongly correlated with the urinary CXCL9 and CXCL10 levels at the time of rejection (r=0.615, p=0.002; and r=0.519, p=0.022, respectively). Among those with T cell-mediated rejections the mean urinary CXCL10 level increased to as high as 258.12 ng/mL. CONCLUSION: Urinary CXCL9 and CXCL10 levels might have a predictive value for T cell-mediated rejection in early post-transplantation period. Measurement of urinary CXCL9 and CXCL10 levels could provide an additional tool for the diagnosis of rejection.

Predictive Value of Interleukin 2 and Interleukin 8 on Early Rejection in Living Related Kidney Transplant Recipients.

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.

Effects of Rituximab on Atherosclerotic Biomarkers in Kidney Transplant Recipients.

INTRODUCTION: Cardiovascular disease is the leading cause of mortality in kidney transplant recipients. Rituximab is widely used in kidney transplantation for a variety of situations, and rituximab may inhibit some cytokines and antibodies that may play an active role in the atherosclerotic process. The aim of the study was to evaluate the efficacy of rituximab on atherosclerosis biomarkers in kidney transplant recipients. METHODS: All patients, 18 years of age and older, who underwent kidney transplantation and received at least 1 dose of 375 mg/m2 rituximab were considered for participation in this study. The primary study endpoint was the development of cardiovascular diseases after rituximab therapy. The secondary endpoint was the onset of cytomegalovirus (CMV) disease or biopsy-confirmed BK virus nephropathy. In addition, comparison of atherosclerosis biomarkers was performed between study and control groups. RESULTS: There were no cardiovascular events observed during follow up. Only 8 patients in the study group suffered from CMV disease during follow up. Serum interleukin 10 levels were significantly higher in the rituximab group compared with the control group, although anti-oxidized low-density lipoprotein levels were lower in the rituximab group compared with the control group, though this did not achieve statistical significance. DISCUSSION: Rituximab treatment may increase the risk of CMV reactivation and decrease lymphocyte counts and interleukin 10 levels; however, significant decreases in all atherosclerotic-related biomarkers have not been shown in our study.

Panel Reactive Antibody Responses Against Influenza Vaccination in Kidney Transplant Recipients.

INTRODUCTION: Seasonal influenza is an important cause of morbidity and mortality in the post-transplant period; therefore, the influenza vaccination has been recommended for all kidney transplant recipients before the influenza season. However, at least theoretically, the introduction of antigens via vaccines may trigger rejection attacks by causing an antibody response. In this study, we examined the development of de novo panel reactive antibody (PRA) development against the influenza vaccine in kidney transplant recipients. MATERIALS AND METHODS: Overall, 41 kidney transplant recipients who received the influenza vaccination and 50 kidney transplant recipients (study group) who refused to receive the influenza vaccination (control group) were enrolled in the study. Following basal biochemistry examination, the inactivated trivalent influenza vaccine was administered intramuscularly. Panel reactive antibodies were screened in all patients before and after vaccination on days 30 and 180. The primary outcome variable was development of de novo panel reactive antibodies. RESULTS: One patient in the study group developed de novo class I and II PRA at 6 months after vaccination (P > .05), while no antibody development was noted in the control group. Graft dysfunction or biopsy-confirmed rejection was not observed during the follow-up period in both groups. CONCLUSION: The influenza vaccination is generally effective and safe in solid organ transplant recipients. The vaccination procedure has the potential to trigger antibody development and occurrence of rejection. Therefore, vaccinated kidney transplant recipients should be monitored more carefully with regard to PRA; if the graft deteriorates, a rapid transplant biopsy should be performed.

Deceased Donor Kidney Transplantation in a Human Immunodeficiency Virus-Infected Recipient: A Case Report.

Human immunodeficiency virus (HIV) infection has traditionally been considered an absolute contraindication for transplantation because immunosuppression will accelerate the disease progression and increase mortality. New antiretroviral agents have given rise to new perspectives and transplantation practices. Now renal transplantation is the gold standard treatment for end-stage renal disease in HIV-infected patients, but increased rejection and toxicity rates and compliance with treatment are important issues. Therefore, patient selection and follow-up should be done carefully in this patient group. Here we present a 51-year-old, male, HIV-infected patient who was diagnosed with HIV at his routine serologic investigation at 2015. Highly active antiretroviral therapy was initiated. One haplotype-matched kidney transplantation from a deceased donor was performed on October 19, 2016. Induction therapy was not administered, and the immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisolone. After 26 months, serum creatinine was 1.1 mg/dL and proteinuria 0.1 g/day. There was no development of donor-specific antibodies. The patient's current HIV viral load remains undetectable (and had been the entire time post-transplantation) while his CD4+ T-cell count currently is 543/mm3.

Influence of uridine diphosphate-glucuronosyltransferases (1A9) polymorphisms on mycophenolic acid pharmacokinetics in patients with renal transplant.

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.

Association Between HLA Antibodies and Different Sensitization Events in Renal Transplant Candidates.

BACKGROUND: 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. METHODS: Anti-HLA class I/II antibody screening tests were performed in 906 renal transplantation candidates with the use of a microbead-based assay (Luminex). RESULTS: 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). CONCLUSIONS: 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.

Prevalence of Human Herpesvirus-8 and BK Polyoma Virus Infections in End-stage Renal Disease and the Influence of Renal Transplantation.

Viral infections lead to significant morbidity and mortality in kidney transplant recipients. We evaluated 49 kidney transplant recipients for human herpesvirus 8 (HHV-8) and BK polyomavirus infections in conjunction with data obtained from 43 donors. The seroprevalence of HHV-8 was 6.9% in donors and 12.2% in recipients. HHV-8 DNA was detected below the limit of quantification (<5000 copies/mL) in a recipient with HHV-8 seropositivity at the pretransplant period and was undetectable at month 3 after transplantation. Transient viruria with BK polyomavirus was recorded in 10.2% of recipients without viremia. Multiple factors contribute to viral reactivation, particularly immunosuppressive treatment. Reduction in maintenance immunosuppression seems beneficial in terms of viral reactivation. At our center, routine use of valganciclovir for antiviral prophylaxis may be effective for the prevention of HHV-8 reactivation.

Corrected Panel-Reactive Antibody Positivity Rates for Hypersensitized Patients in Turkish Population With Calculated Panel-Reactive Antibody Software.

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.

Comparison of Two Different Inhalation Anesthetics on Grafted Kidney Function in Patients Undergoing Renal Transplantation Surgery: Desflurane or Sevoflurane?

BACKGROUND: Anesthetic management of patients during renal transplantation is vitally important for ensuring proper functioning of kidneys that have undergone ischemia-reperfusion damage. The goal of this prospective study was to compare the effects of 2 different inhalation agents (sevoflurane and desflurane) on grafted kidney function in renal transplantation surgery. METHODS: Sixty-five patients who were scheduled for living donor renal transplantation were enrolled in the study. General anesthesia was performed on all patients. Thirty-five pairs of recipients and donors were anesthetized with sevoflurane (group S) and 30 pairs of recipients and donors were anesthetized with desflurane (group D). Each patient's demographic characteristics, immunologic and clinical data, and hemodynamic parameters were recorded. The estimated glomerular filtration rate was calculated in the preoperative period and on postoperative days 1 and 7. The blood samples were collected before the operation and on postoperative days 1 and 7 for measurement of serum creatinine, neutrophil gelatinase-associated lipocalin, and interleukin 18. RESULTS: There were no significant differences in demographic characteristics or immunologic data between group D and group S. Intraoperative heart rate and mean arterial blood pressure were the same between groups. Creatinine, estimated glomerular filtration rate, neutrophil gelatinase-associated lipocalin, and interleukin 18 values did not differ between groups (P > .05) in the preoperative period and postoperative days 1 and 7. CONCLUSIONS: Sevoflurane and desflurane had no adverse effects on grafted kidney functions according to short-term graft outcomes in patients undergoing living donor renal transplantation.

Tac-MMF Versus CsA-MMF/CsA-AZA-Based Regimens in Development of De Novo Complement-Binding Anti-HLA Antibodies After Kidney Transplantation.

BACKGROUND: Immunosuppressive regimens with tacrolimus or cyclosporine A (CsA) were compared for graft-related outcomes in conjunction with complement-binding de novo donor-specific antibodies (DSAs). METHODS: Non-sensitized adult patients without rejection episodes within 3 months after transplantation were screened for the presence of de novo DSAs and C1q binding. Clinical and biopsy data were retrospectively obtained. RESULTS: The analysis included 118 patients (68 tacrolimus, 50 CsA), with mean age and follow-up of 36.1 ± 11.4 and 7.2 ± 4.8 years, respectively. As compared with tacrolimus, the CsA group had higher rates of both class II DSAs and C1q-binding DSAs (20% vs 4.4%, P = .008, and 18% vs 0%, P = .003, respectively). Rates of chronic antibody-mediated rejection (cAMR), proteinuria >500 mg/g, and levels of creatinine both at last visits were also higher in the CsA group (20% vs 0%, P = .002, 30% vs 5.9%, P = .005, 1.67 ± 1.31 vs 1.18 ± 0.45 mg/dL, P = .019, respectively).Class II DSAs and C1q-binding class II DSAs were significantly correlated with the clinical outcomes (creatinine levels, proteinuria, and cAMR). CONCLUSIONS: Compared with tacrolimus, CsA appears to pose a higher risk for the development of de novo anti-HLA antibodies with C1q-binding properties and, consequently, adverse graft-related outcomes.

Evaluation of TH17 and TH1 Immune Response Profile in Patients After Renal Transplant.

BACKGROUND: Renal transplantation (RT) is the best treatment option for patients with end-stage renal disease (ESRD) because it improves both quality of life and survival. However, allograft rejection remains the most important barrier to successful transplantation. Underlying immunologic mechanisms should be understood to develop appropriate treatment strategies. METHODS: In this prospective study, we followed renal transplant recipients for 6 months. The study population comprised 50 recipients of renal transplants, and these were divided into 2 groups: 44 patients with stable graft function (SGF) and 6 patients with rejection (RX). Peripheral blood samples were drawn from patients on the pre-RT day, at post-RT day 7, month 1, and month 6, and on the day of rejection for analysis of the percentages of cytokines interleukin (IL) 17 and interferon (IFN) γ with the use of flow cytometry and enzyme-linked immunosorbent assay. RESULTS: The percentages of intracellular IFN-γ were not significant in the group with RX compared with SGF. Levels of intracellular IL-17 obtained at the 6th month after RT were significantly higher in the RX group than in the SGF group. Plasma levels of pre-RT IL-17 were also higher in the RX group; therefore, it may be a predictive biomarker of acute rejection of renal transplants. CONCLUSIONS: The present study provides information about pre-RT and post-RT cytokine profiles of Turkish patients with ESRD. We consider cytokine analysis to be a valuable biomarker panel in the prevention of rejection and in assisting with new treatment strategies for patients undergoing renal transplant.

Relevance of Flow Cytometric Auto-Crossmatch to the Post-transplant Course of Kidney Transplant Recipients.

INTRODUCTION: The crossmatch test is essential prior to kidney transplantation (tx) to confirm compatibility between the donor and the recipient. However, its results can be misleading due to "undetectable antibodies" in the recipient's serum. To establish if undetectable autoantibodies are responsible for a positive result, an auto-crossmatch test can be performed. In this study, we aim to determine the long-term prognostic value of auto-flow cytometric auto-crossmatch (FCXM) test on kidney survival in kidney tx recipients. MATERIALS AND METHODS: The primary outcome variable was reduced renal function. Secondary endpoints were incidence of biopsy-confirmed chronic antibody-mediated rejection (CAMR) and recurrent glomerulonephritis (GN). RESULTS: There were no differences regarding initial serum creatinine levels between the study and control groups (P = .441). Patients who had positive auto-B FCXM had a significantly reduced renal function compared with the control group (P = .016). Four patients developed biopsy-confirmed CAMR in the study group and 1 patient in the control group (P = .047). Five patients had biopsy-confirmed recurrent GN in the GN study group, and only 1 patient had recurrent GN in the GN control group (P = .026). DISCUSSION: Kidney transplant recipients with positive auto-FCXM test had significantly reduced renal function and a higher incidence of recurrent GN and CAMR compared with the control group. The findings of this study suggest a potential role of auto-antibody causing positive auto-FCXM test result, meanwhile increasing the risk of CAMR, recurrent GN, and new-onset diabetes after tx.

Influence of Proton Pump Inhibitors on Mycophenolic Acid Pharmacokinetics in Patients With Renal Transplantation and the Relationship With Cytochrome 2C19 Gene Polymorphism.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

A Novel Biomarker for Post-Transplant Recurrent IgA Nephropathy.

BACKGROUND: The serum levels of galactose-deficient immunoglobulin (Ig)A1 (Gd-IgA1) represent the most promising candidate biomarker for IgA nephropathy (IgAN). The aim of this study was to evaluate the serum levels of Gd-IgA1 as a novel noninvasive biomarker for post-transplant IgAN recurrence. METHODS: Serum Gd-IgA1 levels of 18 patients with recurrent IgAN were compared with control renal transplant recipients (n = 23) with non-recurrent IgAN and control non-transplant IgAN patients (n = 44) and healthy relatives (n = 11). Serum Gd-IgA1 levels of patients were measured with the use of KM55 enzyme-linked immunosorbent assay (ELISA). The effects of serum Gd-IgA1 concentrations on IgAN recurrence, post-transplant events, and graft survival were evaluated. RESULTS: All recurrent IgAN patients presented with renal dysfunction (mean serum creatinine, 1.62 ± 0.39 mg/dL) and detectable proteinuria at the time of diagnosis. Serum Gd-IgA1 levels of recurrent IgAN patients (8735 ± 10854 ng/mL [log10: 3.71 ± 0.45]) were significantly higher than those of non-recurrent IgAN patients (4790 ± 6089 ng/µL [log10: 3.31 ± 0.64]) (P = .027). Serum Gd-IgA1 levels of non-transplant IgAN patients were significantly higher (8791 ± 8700 ng/µL [log10: 3.79 ± 0.36]) than those of non-recurrent IgAN patients (4790 ± 6089 ng/µL [log10: 3.31 ± 0.64]) and healthy relatives (2615 ± 1611 ng/µL [log10: 3.34 ± 0.27]) (P < .001 and P = .021, respectively). Receiver-operating characteristic curve analysis revealed that the area under the curve for recurrence of IgAN was 0.69 (0.53-0.85) for serum Gd-IgA1 (P = .038). Biopsy-confirmed allograft rejection rates were similar in the recurrent IgAN group [3 (17%)] compared with the non-recurrent IgAN [6 (26%)] group (P = .47). Graft failure rate was not also significantly different in the recurrent IgAN group [4 (22.2%)] compared with the non-recurrent IgAN group [2 (8.7%)] (P = .224). CONCLUSIONS: This novel lectin-independent Gd-IgA1 ELISA that can detect serum Gd-IgA1 in patients with recurrent IgAN can be used as a biomarker for diagnosis and activity assessment of post-transplant recurrent IgAN.

Acquired Acrodermatitis Enteropathica Syndrome in a Kidney Transplant Receipt: A Case Report.

Acrodermatitis enteropathica syndrome (AE) is a clinical entity that results in severe zinc deficiency. It can be genetic or acquired. Acquired AE has been reported in patients with chronic liver disease, malabsorption syndrome, sickle cell anemia, and chronic renal failure. We present a kidney transplant recipient with skin rash and watery diarrhea. The patient had low serum zinc levels, which quickly resolved after zinc supplementation. Skin biopsy showed cytoplasmic pallor and vacuolization and ballooning degeneration of keratinocytes within the superficial epidermis, which may have led to confluent necrosis of keratinocytes. Large amounts of keratinosome-derived lamellae were found in the intercellular spaces in the keratinized area, probably related to disturbance of keratinosome metabolism due to zinc deficiency.

Comparative Analysis of Outcomes of Kidney Transplantation in Patients With AA Amyloidosis and Chronic Glomerulonephritis.

BACKGROUND: Amyloid A (AA) amyloidosis is a multisystemic, progressive, and severe disease. Renal involvement is a prominent feature of the disease, and the outcome of patients on dialysis is poor. We aimed to analyze the outcomes of kidney transplantation in patients with AA amyloidosis in comparison with chronic glomerulonephritis (CGN). METHODS: Charts of patients who underwent kidney transplantation between 1988 and 2012 were reviewed; 41 patients with AA amyloidosis were identified, and 41 age- and sex-matched control patients with chronic CGN were included. Baseline characteristics, immunosuppressive regimens, and transplantation-related outcomes were retrieved using a standardized form. RESULTS: The mean follow-up period was 70.9 ± 44.9 months. The 10-year patient survival was found to be significantly worse in the AA amyloidosis group (62.5%) compared to CGN group (100%) (P = .008). During the follow-up period, three of the 41 patients (9.7%) died of sepsis and one patient died of cardiac complications in the amyloidosis group, whereas there was no patients were lost in the CGN group. The first-year, fifth-year, and tenth-year mean graft survival rates, acute and chronic rejections, and mean creatinine levels at last visits were not significantly different between the groups. Proteinuria >1 g/d, cytomegalovirus and tuberculosis infections, and rhabdomyolysis were recorded at a significantly higher rate in patients with amyloidosis. CONCLUSION: As compared to patients with CGN, patients with AA amyloidosis had a lower patient survival; equal graft survival and rejection rates; and higher risks of developing proteinuria, cytomegalovirus and tuberculosis infections, and rhabdomyolysis.

Effects of diclofenac sodium on the hippocampus of rats with acute subdural hematoma: histological, stereological, and molecular approach.

This study was aimed at evaluating the potential effects of acute subdural hematoma (ASDH) and diclofenac sodium (DS) therapy following ASDH on the rat hippocampus. Twenty-four male Sprague Dawley rats were used and divided into four groups. 0.1 ml of non-heparinized autologous blood from the tail vein of the animals in the non-treatment group (NTG) and treatment group (TG) was injected into the subdural space. The TG received intramuscular diclofenac sodium at a 15 mg/kg dose daily from the postoperative second hour to the seventh day after the operation. The control group (CG) and sham group (SG) were used for control and sham operations, respectively. On the postoperative eighth day, all animals were sacrificed, and the hippocampi of all animals were stereologically and histologically evaluated. Also blood samples of the animals were biochemically analyzed. As a result of the study, the mean number of neurons in CA1, CA2, and CA3 regions of the hippocampus and the total number of neurons were decreased in the hippocampus samples of the NTG and especially the TG subjects. When comparing the second blood samples, there was no difference between the levels of adrenaline and serotonin among the groups. However, after the operation, noradrenalin levels in the treatment group were found to be higher than those of the sham and control groups (p < 0.05). In the NTG and TG, histopathological findings were observed such as Nissl condensation as well as completely dead and indistinguishable neurons with abnormally shaped, shrunken cytoplasm and nuclei. Also necrotic areas on the specimens of the TG were seen. In immunohistochemical sections, c-FOS positivity was decreased in the NTG and especially the TG. Otherwise, PGC-1 positive cells were increased in the NTG and especially the TG. In this study, it was shown for the first time by means of stereological techniques that using DS after ASDH caused a decrease in the number of hippocampal neurons (CA1, CA2, and CA3 regions).

Effects of prenatal diclofenac sodium exposure on newborn testis: a histomorphometric study.

Diclofenac sodium (DS) is used primarily to treat fever and to alleviate pain and inflammation. We investigated the effects of DS exposure during gestation on the testes of rat pups to investigate the safety of its use during the prenatal period. Pregnant rats were separated into control, saline, low dose, medium dose and high dose groups. DS was given between weeks 15 and 21 of gestation. Total numbers of spermatogonia and Sertoli cells were counted in the testes of 7-day-old male rats using the physical disector method. By the end of the study, the total number of Sertoli cells was decreased significantly in a dose dependent manner in the medium and high dose groups compared to controls. No significant differences were found in the total number of spermatogonia in the control, saline and low dose DS groups. Medium and high dose DS administration reduced the total number of spermatogonia compared to other groups. We suggest that prenatal administration of DS can cause deleterious effects on the testis development, especially in high doses.

Is parturition-timing machinery related to the number of inhibitor CD94/NKG2A positive uterine natural killer cells?

PURPOSE: Prematurity is the most common cause of infant mortality and morbidity. To prevent this, the timing of parturition and its mechanisms should be understood. It is likely that inhibitor CD94/NKG2A positive decidual natural killer cells (uNK) provide for the continuation of pregnancy. Here, we aimed to evaluate whether CD94/NKG2A positive uNK cells are highest in elective cesarian section (C/S) (suggesting ongoing gestation), moderate in normal full-term birth, and lowest in pre-eclamptic parturition. METHODS: Of 48 pregnant women, 21 C/S, 16 normal, and 11 pre-eclamptic deliveries were included in this study. Five placentas in each group were assigned randomly. After staining, the volumetric analysis of the placental villi and villous blood vessels was performed via the Cavalieri principle. The CD94/NKG2A positive uNK cells were counted using the physical disector method. RESULTS: The gestation periods and birth weights of the pre-eclamptic deliveries were lower than those of the other two groups. Additionally, the villi and villous vascular volumes were lowest in the pre-eclamptic placentas. As proposed in our hypothesis, the inhibitor CD94/NKG2A positive uNK cells were the highest in the C/S, moderate in the normal, and lowest in the pre-eclamptic placentas. CONCLUSIONS: These data suggest that CD94/NKG2A positive uNK cells are related with the continuation of pregnancy, and that our human model could be used to search for parturition-timing machinery. We believe that CD94/NKG2A positive uNK cells are also related to the timing of birth.