Search

© 2023 Pan-Arab Association of GastroenterologyBackground and study aims: Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for chronic kidney disease (CKD). Previous studies argued that leptin levels increase significantly with the progression of CKD. But the association between leptin and CKD has not been investigated in patients with NAFLD. Therefore, we conducted this study to establish whether increased leptin level is associated with CKD in NAFLD patients. Patients and methods: In our prospective study with a follow up period of six months thirty-five teetotaller biopsy-proven NAFLD patients were divided as groups with mild, versus advanced, fibrosis. Liver fibrosis was also assessed with Fibroscan. Serum leptin levels were measured by radioimmunoassay. For insulin resistance we used the homeostasis model assessment method (HOMA-IR). For the kidney function, we used the abbreviated formula Modification of Diet in Renal Disease (MDRD) formula, which estimates GFR. For statistical analysis, Student\"s-t test, Mann-Whitney test, linear regression-binary logistic regression analyses and the ROC curve analysis were used. Results: Advanced fibrosis and increased HOMA-IR were risk factors for decreased eGFR. Leptin correlated inversely with advanced fibrosis (p: 0.03) and low leptin was a risk factor for CKD (p: 0.02). In ROC curve analysis, advanced fibrosis and low leptin were risk factors for decreased eGFR (p: 0.007 and 0.004, respectively). Low leptin level was dependently associated with decreased eGFR. Conclusion: Advanced fibrosis in NAFLD patients is a risk factor for CKD. Leptin correlated inversely with advanced fibrosis. Unlike the previous studies, which were not performed in NAFLD patients, we found decreased leptin in NAFLD patients with decreased eGFR. Low leptin level was found to be a dependent predictor for differentiating NAFLD patients with high risk for CKD.

Gastrointestinal bleeding remains the leading cause of morbidity and mortality for patients who need hemodialysis treatment. Our aim was to evaluate patients who needed hemodialysis and presented with bleeding during their hospital stay (uremic bleeding patients). Factors that increased the risk of bleeding and death were evaluated. Additionally, uremic bleeding patients were compared to non-uremic bleeding patients regarding gastrointestinal findings. Fifty-one uremic bleeding patients were compared to two control groups which included uremic (hemodialysis dependent and non-bleeding) and non-uremic (no renal insufficiency and bleeding) patients. NSAIDs and anti-ulcer drug usage were more common in uremic bleeding and in uremic non-bleeding groups, respectively. Dialysis vintage was longer in uremic bleeding group. Comparison of uremic bleeding and non-bleeding uremic patients regarding the usage of ACEI or ARB drugs yielded non-significant results. Acute kidney injury, lower plasma albumin level and high CRP level were significantly increased the risk of mortality in uremic bleeding patients. Hospital stay more than 1 week was the only strong factor for mortality when multivariate analysis was performed. Gastroduodenal and duodenal ulcers were significantly detected in uremic bleeding and non-uremic bleeding patients; respectively. Hemodialysis patients presenting with gastrointestinal bleeding should be evaluated regarding use of prescriptions and efforts should be done in order to shorten their hospital stay and decrease their mortality. Effect of ACEI or ARB drugs should also be evaluated in future studies.

Cytotoxic flow cytometric crossmatch (cFCXM), identified by detecting complement-mediated cytotoxic cell death in addition to the capability of showing the alloantibodies binding onto lymphocytes at the same time, can reduce the necessary time and workload in evaluating alloantibodies. More data from clinical samples are needed for cFCXM to be accepted by tissue typing laboratories. In this study, we compared cFCXM with complement-dependent lymphocytotoxicity and standard flow cytometric crossmatch in 41 renal pretransplant patients. A comparison of the obtained data was performed using Spearman's correlation test. We found that cFCXM showed no statistically significant differences with complement-dependent lymphocytotoxicity and flow cytometric crossmatch. We believe that cFCXM can be used in clinical laboratories in the near future following intra-laboratory validation.

Brown tumors are focal bone lesions, encountered in patients with uncontrolled hyperparathyroidism. They can be located in any part of the skeleton. Clinically significant lesions in the craniofacial bones are rare. Craniofacial involvement may cause facial disfiguration and compromise social ease of the patient and normal functions, such as chewing, talking, and breathing. In this case report, we present a patient with a brown tumor of the craniofacial bones provoked by secondary hyperparathyroidism and review the last 10 years of craniofacial brown tumors associated with secondary hyperparathyroidism in the English literature.

BACKGROUND Sensitization is one of the most important barriers against transplantation. Our aim was to evaluate the sensitization status of our patients awaiting cadaveric transplantation and to identify factors causing sensitization. MATERIAL AND METHODS A total of 140 patients on the cadaveric waiting list during January 2014 were included in this retrospective cross-sectional study. The parametric t-test and the non-parametric chi-square test were used to detect differences between PRA-positive and -negative patients. Multivariate analysis was used to identify factors associated with PRA positivity. One-way analysis of variance was used to compare PRA-negative and -positive results. RESULTS Anti-HCV positivity (p=0.040), history of transfusion (p=0.041), and mean number of blood product transfused (p=0.047) were significantly related to class 1 PRA positivity. History of transfusion (p=0.038) and mean number of blood product transfused (p=0.044) were related to class 2 PRA positivity. The multivariate analysis indicated that transfusion and more than 5 units of blood product transfused were related to either class 1 or class 2 PRA positivity. No associations were found between PRA positivity and pregnancy, transplantation, age, sex, infection, abortion, cardiovascular disease, diabetes mellitus, hepatitis B, or time spent on dialysis and being on the transplantation waiting list. CONCLUSIONS Anti-HCV positivity and transfusion are risk factors for sensitization. Particular emphasis should be given to sensitization and its prevention to reduce waiting time for transplantation.

Aim Patients displaying flow cytometric crossmatch results within the grey zone of positivity are hard to evaluate, especially if they are undergoing their first transplantation. For these patients assays of donor-specific anti-HLA (human leukocyte antigen) antibodies with complement-fixing properties to cause cell lysis are important for antibody-mediated rejection and graft failure. The aim of this study was to detect the relevance of serum C1q-binding antibodies detected in renal recipients with grey zone crossmatch reactivity who were considered to show low levels of sensitization against their potential donors. Method This study includes 114 patients who were admitted for their first renal transplantation between September 2009 and August 2011, including 33 subjects considered by flow cytometric cross-match to be the sensitized group, whereas the remaining 81 recipients had negative results. We analyzed the accumulation of serum the immunoglobulin (Ig)G bound C1q on HLA-coated flowcytometric panel reactive antibody (FlowPRA) beads. The serum samples were retrospectively analyzed with [C1q]FlowPRA (HLA class I and II), which were collected during the pretransplantation period every 6 months and every week posttransplantation within the first month and every 3 months thereafter. All serum samples were analyzed for the presence of anti-FlowPRA IgG alloantibody. We compared the C1q FlowPRA-positive and-negative groups for the number of posttransplantation days that the serum creatinine level was below Results With a mean follow-up of 492 ± 84 days, there was a significant difference between flow cytometric crossmatch results and creatinine decrease rate ( P = .02). The serum creatinine decrease rates of the 9 C1q-positive versus the 15 C1q-negative subjects showed significant difference ( P Conclusion C1q-binding antibody analysis shows the presence of serum antibodies capable of complement binding and antibody-mediated rejection, which could be useful to assess rejection risk among the “grey zone” of renal recipients with low levels of sensitization against their donors.

Objective. Rapid loss of vertebral or hip mineral density after renal transplantation is a major complication which occurs within 6―12 months. The aim of this study was to evaluate risk factors contributing to bone disease in the early stage after renal transplantation and the effect of vitamin D receptor (VDR) gene polymorphisms. Methods. We prospectively followed for up to 12 months 44 patients (29 men and 15 women) with end-stage renal disease who underwent kidney transplantation. All patients received prednisone with either cyclosporine (CsA)/mycophenolate mofetil (MMF) or tacrolimus (Tac)/MMF therapy. Spine, hip, and whole body bone mineral density (BMD) was measured at 12 months after transplantation. According to World Health Organization recommendations, our patients were categorized as normal, osteopenic, or osteoporotic BMD levels. VDR alleles were genotyped as BB, Bb, or bb by polymerase chain reactions based on polymorphism at the Bsm I restriction site. Results. Forty-six percent of patients were normal, 43% osteopenic, and 11% osteoporotic. Significant risk factors for osteoporosis among renal transplant recipients were younger age and pretransplant high intact parathyroid hormone (iPTH) levels. (P values .045 and .027, respectively). According to polymorphic group categorization, posttransplant serum Ca was significantly higher in patients with BB or Bb genotype than in those with bb genotype (P = .012). Although there was no statistical significance regarding iPTH levels, it was higher among Bb+BB than the bb genotype group. Also, first-year BMD analysis after transplantation according to Bsm I polymorphism showed significant differences in femur BMD levels according to the dual classification of polymorphism (P < .05). The BMD levels in the bb group was higher than in the Bb+BB group. Conclusions. Although high pretransplant iPTH levels and younger age enhanced posttransplant bone loss, functionally different alleles of the VDR gene may modulate bone turnover during the first year after renal transplantation.

Background: Liver biopsy is an imperfect gold standard for assessing the disease severity in hemodialysis patients with chronic hepatitis C. Our purpose was to compare the accuracy of the FibroTest (FT) and ActiTest (AT) with liver biopsy and the AST-to-platelet ratio index (APRI) in determining hepatic fibrosis and necroinflammatory activity in hemodialysis patients with hepatitis C virus (HCV). Methods: The FT-AT index combining 6 biochemical markers was assessed in 33 hemodialysis patients with HCV. Liver fibrosis and necroinflammatory activity was staged and graded according to the METAVIR scoring system. Results: The accuracy of FT-AT versus biopsy was 0.46 for significant fibrosis and 0.36 for severe necroinflammatory activity. The FT index had a positive predictive value of 20% for scores greater than 0.6 and a negative predictive value of 45% for scores less than 0.2. Eleven of the 33 patients had scores ≤0.2, 6 had significant fibrosis on biopsy. Four out of 5 patients with FT scores >0.6 had mild fibrosis. APRI correlated well with the biopsy. Conclusion: The FT-AT test does not seem to be a reliable noninvasive marker for the prediction of necroinflammatory activity and fibrosis in hemodialysis patients with HCV and cannot be used as an alternative to either liver biopsy or APRI.

Objective To analyze the dermatologic lesions and possible effects of immunosuppression treatment and p53 gene mutations on dermatologic findings in renal transplant recipients. Materials and Methods The study included 163 renal transplant recipients. After dermatologic examination, cultures, and histopathologic and genetic analyses were performed. A single-strand conformation polymorphism technique was used to analyze p53 gene mutations. Patients were categorized into 3 groups according to time since the transplantation procedure. Results were analyzed using the χ 2 test, using a software program (SPSS version 13.0; SPSS, Inc, Chicago, Illinois). Results Mean (SD) age of the 163 transplant recipients (65 women and 98 men) was 40 (11) years, and posttransplantation follow-up was 65 (55) months. The most frequently observed drug-related lesion was hypertrichosis, in 46 of 150 patients. Of 115 lesions, the most commonly observed were verruca vulgaris (n = 34) from viruses, and pityriasis versicolor (n = 21) from superficial fungal infections. Of the total group, 20 patients (12.2%) were mutation carriers. Compared with the entire cohort, the group with premalignant lesions demonstrated more p53 mutations (11% vs 50%; P = .004). Patients given cyclosporine therapy exhibited more premalignant or malignant cutaneous lesions compared with patients who received other agents ( P = .03). Conclusion Patients carrying p53 mutations developed a malignant lesion in the late posttransplantation period, which suggests the importance of prediction of risk.

Aim: To evaluate the serum alanine aminotransferase (ALT) variabilities in nonalcoholic fatty liver disease (NAFLD) and correlate it with hepatocyte apoptosis and oxidative stress parameters. Methods: 24 patients with NAFLD and normal ALT were compared with 26 subjects with NAFLD and elevated ALT. Liver oxidative stress was estimated on the basis of malondialdehyde, superoxide dismutase and glutathione. Immunohistochemistry was performed for activated caspase 3 and 8, nuclear factor-κB, antiapoptotic Bcl-2 protein and serum TNF receptor levels were measured. Results: The mean caspase 3 and 8 activity scores, oxidative stress parameters, necroinflammatory grade and prevalence of severe fibrosis were comparable across the groups with normal versus elevated ALT. Patients with nonalcoholic steatohepatitis had significantly higher caspase 3 and 8 activity (percentage of cells with positive staining per high power field), and serum malondialdehyde (mmol/l) levels than those with simple steatosis. ALT elevation was not a risk factor for advanced necroinflammatory grade and fibrosis. A receiver operating characteristic curve did not demonstrate sensitivity and specificity for discriminative power of ALT. Conclusion: Apoptosis and oxidative stress are the main processes contributing to disease progression in NAFLD. ALT values do not correlate with the parameters of apoptosis and oxidative stress. The disease severity can only be determined by liver biopsy.

Insulin resistance is commonly observed in uremic patients. Glucose-based peritoneal dialysis solutions have long-term metabolic complications like hyperinsulinemia, hyperlipidemia, and obesity. The purpose of this study was to examine the insulin resistance in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with standard glucose and icodextrin containing solutions. The entire non diabetic CAPD patients of our center were studied: forty-four patients in all who were on CAPD treatment for 36.2 +/- 23.7 months. Twenty-seven of them (11 male and 16 female) with a mean age of 46 +/- 16 years were treated with standard glucose solutions (glucose group). The other 17 patients (10 male and 7 female) with a mean age of 49 +/- 16 years were treated with standard glucose solutions during the day and icodextrin dwell during the night, for a median of 12 +/- 6.3 months (icodextrin group). Morning fasting serum insulin levels were 20.59 +/- 17.86 in the glucose group and 10.15 +/- 6.87 in the icodextrin group (p = 0.0001). Homeostasis Model Assessment Method scores of the glucose group were significantly higher (4.8+/-4.1 vs 2.3+/- 1.7; p = 0.025) than the icodextrin group. A significant positive correlation of HOMA score with insulin, fasting plasma glucose, and triglyceride levels were found in HOMA (IR+) patients. Twenty patients of the icodextrin group (74%) and 15 patients of the glucose group (88%) were hypertensive, but there was no statistically significant difference between the two groups (p = 0.13). The groups showed no significant differences for body mass index and serum levels of glucose, total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, triglyceride, intact parathyroid hormone (iPTH), and fibrinogen. In conclusion, the use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.

Introduction There is an increasing gap between organ supply and demand for cadaveric transplantation in our country. Our aim was to evaluate factors affecting selection of patients on waiting list at our hospital. Method Patients who have been waiting on list and who were transplanted were compared in order to find factors, which affected the selection of patients. Non-parametric Mann-Whitney U test was used for comparison and cox regression analysis was used to find the risk factors that decrease the probability of transplantation in this retrospective case-control study. Results Patients in the transplanted group were significantly younger, had relatively lower body mass index than the awaiting group. Cardiovascular diseases were more in the awaiting group than the transplanted group. There was no patient with diabetes in transplanted group, despite fifteen diabetic patients were in the awaiting group. Selected patients had lower immunologic risk with regard to peak panel reactive antibody levels. No significant difference was found for gender, hypertension, hyperlipidemia, viral serology, time spent on dialysis and on waiting list between two groups. With cox regression analysis female gender, older age, diabetes mellitus, high body mass index, positive hepatitis B serology and high levels of peak class 1–2 peak panel reactive antibody positivity were found as risk factors that decrease the probability of transplantation. Conclusion A tendency for selection of low risk patients was found with this study. Time and energy consuming complications and short allograft survival after transplantation in high risk patients and the scarcity of cadaveric pool in our country may contribute to this tendency.

A letter in response to: Yilmaz Y, Kurt R, Kalayci C. Apoptosis in nonalcoholic steatohepatitis with normal aminotransferase values: zooming in on cytokeratin 18 fragments. Biomarkers Med. 4(5), 743–745 (2010).

Aim. The aim of this study was to evaluate the long-term medical risks of living-related donors in our center. Patients and Methods. 185 living-related donors participated in the study. The factors assessed were creatinine clearance rate (CrCl), serum creatinine (SCr), BUN, hematocrit levels, proteinuria, microalbuminuria and hypertension rates, and renal parenchyma thickness and kidney dimensions predonation as well as at the last follow-up. In addition, we examined postoperative complications. A lombotomy incision was the choice for donor nephrectomy procedure routinely. Results. The mean length of hospital stay after donor nephrectomy was 3.2 ± 0.6 days (range, 2-5 days). Seven donors readmitted during the first month after operation with surgical site infection were treated successfully. Four donors were reoperated for incisional hernia repairs and discharged without complication. The mean follow-up period was 61.6 ± 50.4 months (range, 2-180 months). Mean ages of the donors at operation and at the last follow-up were 50.9 ± 12.7 years (range, 20-81 years) and 56.5 ± 11.9 years (range, 29-77 years), respectively. The male-to-female ratio was 0.69. Mean SCr levels and CrCl rates predonation and at the last follow-up were 0.83 ± 0.22 mg/dL versus 1.1 ± 0.2 mg/dL (P

Alkaptonuria (AKU; McKusick No. 203500), a rare hereditary disorder of the phenylalanine catabolism, was the first disease to be interpreted as an inborn error of metabolism (A. E. Garrod, 1902, Lancet 2: 1616-1620). AKU patients are deficient for homogentisate 1,2-dioxygenase (HGO; EC 1.13.11.5). This enzymatic deficiency causes homogentisic aciduria, ochronosis, and arthritis. Recently we cloned the human HGO gene and showed that AKU patients carry two copies of a loss-of-function HGO allele. Here we describe the complete nucleotide sequence of the human HGO gene and the identification of its promoter region. The human HGO gene spans 54,363 bp and codes for a 1715-nt-long transcript that is split into 14 exons ranging from 35 to 360 bp. The HGO introns, 605 to 17,687 bp in length, contain representatives of the major classes of repetitive elements, including several simple sequence repeats (SSR). Two of these SSRs, a (CT)n repeat in intron 4 and a (CA)n repeat in intron 13, were found to be polymorphic in a Spanish population sample. The HGO transcription start site was determined by primer extension. We report that sequences from -1074 to +89 bp (relative to the HGO transcription start site) are sufficient to promote transcription of a CAT reporter gene in human liver cells and that this fragment contains putative binding sites for liver-enriched transcription factors that might be involved in the regulation of HGO expression in liver.

Although antithymocyte globulin (ATG) has been used for years, its ideal dose and administration period is obscure. Herein, we sought to use the CD3(+) cell count to detect the optimal ATG dosage.Twenty-one patients who underwent cadaveric donor renal transplantation from January 2009 to January 2012 received a 1 mg/kg ATG initial dose at the time of the operation. Patients were randomized into 2 cohorts. Group 1 (n = 11) received ATG according to the clinical and total lymphocyte count and group 2 (n = 10), the dose was tailored according to the CD3(+) cell count. We compared the total and daily ATG dosages, ATG administration period, side effects of ATG, the number of days to a serum creatinine level2 mg/dL, graft function at 3 months, acute rejection episodes, infection rates, costs of CD3(+) analysis, and ATG amounts.Both groups showed similar gender, age, and human leukocyte antigen matching data. There was no difference in presensitizing events or panel-reactive antibody class 1 and 2 levels. The number of days to a serum creatinine level of2 mg/dL was 11 ± 1.5 for group 1 versus 10.4 ± 0.8 for group 2 (P = .45). Between groups 1 and 2, there was a significant difference between the mean total (P = .031) and mean daily ATG dosages (P = .006). We used a total dose of 3800 mg ATG for group 1 and 2200 mg for group 2 and for the group 2 who underwent 43 CD3(+) cell counts. The expenditure per patient was 20% higher among group 1 than group 2.Determination of appropriate ATG dosages by CD3(+) cell counts was useful, reliable, and cost effective.

Purpose Acute and chronic humoral injuries in renal tranplant recipients are the main reasons for graft rejection and failure. Histological and clinical characteristics of humoral rejection and symptoms are variable and not always helpful for differential diagnosis. Clinical monitoring of the allograft, an elevated serum panel-reactive antibody (PRA), and the presence of donor-specific antibody (DSA) during immune monitoring as well as C4d staining of biopsy material can establish the differential diagnosis. Even without a cellular component, humoral rejection reaction is serious because the target tissue is the graft endothelium. Because the kidney graft has a rich vascular structure this attack causes permanent injury to the kidney in the long term. Graft dysfunction in this setting is usually more severe, requiring dialysis therapy, compared with acute cellular reactions. Positive C4d staining of peritubular capillaries in biopsy material represent a hallmark of complement-dependent cytotoxicity, supporting the diagnosis of humoral rejection. We analyzed C4d staining as a hallmark of humoral rejection. Methods From 2009 to 2011, we analyzed the relationship between pathological findings of C4d immunohistochemistry staining and the clinical outcomes of 45 kidney transplant recipients who underwent a kidney biopsy because of graft dysfunction due to possible humoral rejection. Results Biopsy specimens of 15 patients stained C4d positive; the remaining 30 showed negative results. Intravenous steroids, PP + IVIG with or without antithymocyte globulin (ATG), was administered for treatment. Sixty six percent (n = 10) of patients were C4d positive with 16% (n = 5) of those showing C4d-negative biopsy results, losing their grafts, and returning to hemodialysis. Conclusions C4d staining refractory humoral rejection injury was related to poor graft outcomes.