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.

The Relationship of Serum Leptin and Ghrelin Levels with Craving and Withdrawal in Opioid Use Disorder.

Objective: This study aims to investigate plasma levels of leptin, acyl ghrelin, and unacylated ghrelin during heroin withdrawal in patients with opioid use disorder (OUD) with regard to the relationship of these levels with craving and their changes over time. Methods: This study included 28 male patients diagnosed with OUD according to DSM-5 diagnostic criteria who received inpatient rehabilitation. The control group included 28 healthy male volunteers with characteristics similar to the patient group. Plasma leptin, acyl ghrelin, and unacylated ghrelin levels of the patients were measured 3 times throughout the study by collecting blood on the first day, the seventh day at the end of the detox, and the twenty-first day. Blood was collected only once from the control group to determine their plasma leptin, acyl ghrelin, and unacylated ghrelin levels. Results: Our study did not determine any statistically significant differences between patients with OUD and healthy controls with regard to plasma leptin, acyl ghrelin, and unacylated ghrelin levels on the first, seventh, and twenty-first days of withdrawal. Plasma levels of leptin, acyl ghrelin, and unacylated ghrelin did not significantly correlate with craving scores. Conclusion: This study does not support the hypothesis that plasma leptin, acyl ghrelin, and unacylated ghrelin levels are markers in those with OUD. Further research, particularly in humans, is recommended to replicate and expand on the findings of the current literature.

Levels of TNF alpha, Soluble TNF Receptors (sTNF-R1, sTNF-R2) in Bipolar Disorder.

INTRODUCTION: Current evidence suggests that pro-inflammatory cytokines, particularly tumor necrosis factor alpha (TNF-α) may play an important role in the pathophysiology of bipolar disorder (BD). Our study aims to compare BD patients and controls in terms of serum TNF-α, soluble tumor necrosis factor receptor 1 and soluble tumor necrosis factor receptor 2 (sTNF-R1, sTNF-R2) levels in different phases of BD. METHODS: Eighty-three patients with BD type 1 (27 manic, 22 depressive and 34 euthymic) and twenty-nine healthy controls were included in the study. Serum levels of TNF-α, sTNF-R1, sTNF-R2 levels were evaluated with ELISA kit. RESULTS: Levels of sTNF-R1 were showed a statistically significant difference between groups. Levels of sTNF-R1 were higher in depression or mania patients than euthymia patients and control subjects. A statistically significant difference in the serum level of sTNF-R1 between patients in acute episode (mania and depression) group and stabile (patients in euthymic episode and controls) group was found in logistic regression analysis. The probability of having acute episode increased threefold for each unit increase in serum level of sTNF-R1. There was no statistically significant difference between the mean serum values of TNF-α and sTNF-R2 between the groups. CONCLUSIONS: sTNF-R1 production was different between acute episode patients and controls or stable BD patients. The result of this study confirms that TNF-R1 may be a state marker representing disease activity for BD.

Orthostatic proteinuria: an overestimated phenomenon?

BACKGROUND: Although orthostatic proteinuria (OP) is the most common cause of childhood proteinuria, excluding transient proteinuria, data regarding prevalence and long-term prognosis are limited. We aimed to determine prevalence of OP in healthy schoolchildren evaluating relationships with age, gender and body mass index, and determine follow-up. METHODS: A total of 1701 healthy children aged 6-15 years were selected using a population-based, stratified, cluster-sampling method; and random urine samples were taken. For proteinuria ≥ 1+ in first urine samples, second and third random samples were taken at least 2 weeks apart to exclude transient proteinuria. For continuing proteinuria after third samples, first morning urine samples were collected. Cases where proteinuria was not detected in first morning urine samples were diagnosed as OP. RESULTS: Sixty-four of 1701 children (3.7%) had proteinuria on first random urine samples. After second and third urine samples, proteinuria persisted in only 16 (0.94%). OP was detected in 11 (0.65%). Prevalence of OP tended to decrease with increasing BMI, though not statistically significant. All 7 cases with OP who were re-evaluated later, had no proteinuria 3 years after diagnosis. CONCLUSIONS: Prevalence of OP in our study was lower than the literature. At least three random urine samples should be taken to exclude transient proteinuria in an asymptomatic child/adolescent before making a diagnosis of OP using first morning urine samples. OP is a benign condition and resolves spontaneously in most cases. Underweight children had a tendency for OP compared with overweight and obese children; however, further studies with larger number of patients are needed.

Tacrolimus Variability: A Cause of Donor-Specific Anti-HLA Antibody Formation in Children.

BACKGROUND AND OBJECTIVES: The most important determinant of long-term graft survival in renal transplantation is adequate immunosuppression. Inadequate immunosuppression may lead to graft loss due to the presence of anti-HLA antibody. The aim of this study was to investigate the effect of variability in tacrolimus blood concentration on anti-HLA antibody development in pediatric recipients of living-donor renal transplants. METHODS: Pediatric recipients of living-donor renal transplants were retrospectively evaluated. Patients with a minimum of two years of follow-up who were administered tacrolimus were included in the study. Patients who had pretransplant anti-HLA antibody were excluded. Variability in tacrolimus blood concentration was assessed using the coefficient of variation ("tacrolimus CV") method. Tacrolimus CV was calculated separately for the first 6 months post-transplant, between 6 and 12 months post-transplant, and from the end of the first year post-transplant to the last follow-up. We constructed receiver operating characteristic (ROC) curves of the tacrolimus CV for each group to find the best cutoff value. RESULTS: A total of 67 patients (including 48 males; 72%) with a mean age of 15.16 ± 4.43 years were included in the study. Anti-HLA antibody positivity was detected in 12 patients (18%). More than three HLA mismatches and the presence of acute cellular rejection correlated with the development of anti-HLA antibody (p = 0.056, 0.009). Tacrolimus CVs for the three periods were 0.37 ± 0.11, 0.31 ± 0.18, and 0.35 ± 0.12, respectively. The cutoff value of tacrolimus CV for anti-HLA antibody development was calculated as 0.32 with a sensitivity of 90.91% and specificity of 50.94% [AUC (area under the curve) 0.713, p = 0.023]. During the second 6-month period and after a  year post-transplant, the percentage of patients with tacrolimus CV > 0.32 was significantly higher in the anti-HLA antibody positive group than in the antibody negative group (67% vs 31%, p = 0.027; 83% vs 47%, p = 0.033). The eGFR (estimated glomerular filtration rate) was similar for the anti-HLA antibody negative and positive groups (78.72 ± 2.86 vs 77.45 ± 8.08, p > 0.05). CONCLUSION: High tacrolimus concentration variability appears to be associated with anti-HLA antibody formation in pediatric recipients of living-donor renal transplants.

Prealbumin and Retinol Binding Proteins Are Not Usable for Nutrition Follow-Up in Pediatric Intensive Care Units.

PURPOSE: Feeding children is a problem in pediatric intensive care units (PICU) and it is difficult to know the correct amount. The purpose of this study is to evaluate if prealbumin or retinol binding proteins (RBP) are effective relative to daily enteral nutrition, without being affected by severity of diseases or infections and can be used to follow up nutritional amount. METHODS: This is a prospective observational study that includes 81 patients admitted to PICU in Akdeniz University with estimated duration >72 hours, age between 1 month and 8 years. Daily calorie and protein intake were calculated and prealbumin, RBP and C-reactive protein (CRP) levels were measured on the first, third, fifth and seventh mornings. RESULTS: We find moderate correlation between daily calorie intake and prealbumin levels (r=0.432, p<0.001), RBP levels and daily protein intake (r=0.330, p<0.001). When we investigated the relationship between changes of prealbumin, RBP, CRP, calorie and protein intake during intensive care stay, we found that increase of Prealbumin and RBP levels are explained by decrease of CRP levels (r=-0.546 and -0.645, p<0.001) and not with increase of nourishment. CONCLUSION: Even adjusted for PRISM3, age and CRP, prealbumin and RBP are correlated with last 24 hours' diet. However, it is not convenient to use as a follow up biomarker because increase of their levels is related with decrease of CRP levels.

Mass spectrometric quantification of urinary human liver fatty acid binding protein in renal transplant recipients.

RATIONALE: Urinary liver fatty acid binding protein (L-FABP) has been evaluated as a promising early biomarker of renal ischemia in human kidney transplant patients. The use of L-FABP in clinical practice requires that this biomarker be associated with an analytical method that combines specificity, accuracy and robustness. This study aimed to evaluate an optimized multiple reaction monitoring (MRM) method using ultrafast liquid chromatography coupled with tandem mass spectrometry to measure urinary L-FABP levels in renal transplant recipients. METHODS: Purified recombinant human L-FABP tryptic standard was analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS/MS) and liquid chromatography (LC)/MS/MS to select for peptides that provided specificity and adequate response in developing an MRM method for urinary L-FABP quantification. Human urine samples collected from kidney transplant recipients were isolated, concentrated, precipitated and trypsin digested before mass spectrometric analysis of L-FABP. L-FABP levels were also measured in urine samples by enzyme immunoassay. RESULTS: The tryptic peptide ion MH(+) of (50) FTITAGSK(57) (m/z 824) provided an adequate signal and was used for quantification of L-FABP under conditions employed for LC/MS/MS analysis. MALDI-TOF-MS/MS spectra obtained by collision-induced dissociation of the parent MH(+) ion (50) FTITAGSK(57) resulted in a y3 product ion that was used for quantitative analysis by the MRM method. Urinary L-FABP content measured by both ELISA and LC/MS/MS after transplantation was significantly higher compared to before transplantation levels. The Spearman correlation coefficient between the two methods was statistically significant. Intra-day and inter-day coefficients of variation provided good repeatability and reproducibility for validation of LC/MS/MS analysis. CONCLUSIONS: LC/MS/MS quantification of L-FABP may provide a new reference method to determine changes in this potential biomarker in human kidney transplant patients.

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.

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.

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

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 m(2) (Group 1, n = 103) and > 60 mL/min/1.73 m(2) (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.

Comparison of Cystatin C and ß-Trace Protein Versus 99mTc-DTPA Plasma Sampling in Determining Glomerular Filtration Rate in Chronic Renal Disease.

UNLABELLED: Glomerular filtration rate (GFR) is the best indicator of renal function. The gold standard for GFR measurement is inulin clearance. However, its measurement is inconvenient, time-consuming, and costly. Thus, in both scientific studies and routine clinical practice nuclear medicine methods ((99m)Tc-diethylenetriaminepentaacetic acid [(99m)Tc-DTPA] and (51)Cr-ethylenediaminetetraacetic acid [(51)Cr-EDTA]) are preferred, and they correlate strongly with inulin clearance. In addition, cystatin C and ß-trace protein have also recently been used for this purpose. In the literature, however, data are limited about the clinical value of cystatin C and ß-trace protein in GFR measurement in chronic renal disease (CRD), and the results have been inconclusive. In this study, we aimed to determine the efficiency of cystatin C and ß-trace protein in the determination of GFR in CRD patients. METHODS: Eighty-four patients with CRD were included in the study (59 men and 25 women; age range, 21-88 y; mean age, 61 y). GFR was calculated using the gold-standard (99m)Tc-DTPA 2-sample plasma sampling method (TPSM) and 2 alternative methods: a formula using cystatin C and a formula using ß-trace protein. The correlation between TPSM and the cystatin C and ß-trace protein methods was assessed, and Bland-Altman analysis was used to graph scatterplots of the differences at a confidence interval of 95% (mean difference ± 1.96 SDs). RESULTS: GFRs calculated using both alternative methods correlated strongly with those calculated using the gold standard. However, the correlation was stronger for the cystatin C method than for the ß-trace protein method, and neither method produced reliably consistent GFRs. CONCLUSION: This study demonstrated that cystatin C and ß-trace protein do not reflect GFR with sufficient accuracy.

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.

Prevalence of metabolic syndrome in women with rheumatoid arthritis and effective factors.

PURPOSE: Metabolic syndrome (MS), which is framed by cardiovascular risk factors such as hypertension, obesity, glucose intolerance and dyslipidemia, is thought to be associated with the rheumatic diseases. The aim of this study is to examine the frequency of metabolic syndrome (MS) and insulin resistance in patients with rheumatoid arthritis (RA) and to examine the effect of the inflammation symptoms, disease activity and drugs used in treating RA on insulin resistance and presence MS. METHOD: One hundred women patients diagnosed with RA according to the American College of Rheumatology (ACR) diagnosis criteria and 100 healthy women were included in the study as controls. Insulin resistance were evaluated using the homeostasis model assessment for insulin resistance (HOMA-IR) method and MS was diagnosed according to two Metabolic Syndrome definitions (National Cholesterol Education Programme 2004, International Diabetes Federation). The disease activity of RA was evaluated by the disease activity score including 28 joints (DAS28). RESULTS: In total, 27% and 33% of the RA patients and 28% and 44% of the control group patients according to the diagnostic criteria used were also MS patients. There was no significant difference between the RA and control groups in MS frequency and insulin resistance according to two diagnostic criteria used. The DAS28, erythrocyte sedimentation speed (ESS) and serum uric acid levels in the RA patients with MS were significantly higher than those of the RA patients without MS. The prevalence of MS In patients with RA using methotrexate (MTX) was significantly lower than without RA. Other drugs used in treatment of RA had no effect on the prevalence of MS in patients with RA. CONCLUSION: Controlling inflammation and disease activity can reduce the MS frequency of RA patients and MTX treatment also may be a protective factor against MS.

A multicenter nationwide reference intervals study for common biochemical analytes in Turkey using Abbott analyzers.

BACKGROUND: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality. METHODS: Blood samples were collected nationwide in 28 laboratories from the seven regions (≥400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA). RESULTS: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and γ-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI. CONCLUSIONS: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.

Cerebrospinal fluid cystatin C levels following treatment for aneurysmal subarachnoid hemorrhage.

AIM: To investigate the changes of cerebrospinal fluid (CSF) cystatin C (CC) levels associated with the postoperative ischemic conditions and prognostic outcome in patients with aneurysmal subarachnoid hemorrhage (SAH). MATERIAL AND METHODS: The study group consisted of 40 patients with microsurgically clipped intracranial aneurysms (IA's) and 22 control CSF samples. In patients, CSF samples were taken from the lumbar intrathecal catheter for CC measurement, at the beginning of operation, immediately after the operation (early postoperative), and the first postoperative day (late postoperative). RESULTS: CC levels in three periods were significantly higher in patients with Hunt-Hess scores of 4, 5 than 1, 2, 3. There was a significant difference between the CC concentrations on the first postoperative day and controls. In patients who developed focal cerebral ischemia, CC levels at early and late postoperative periods were significantly higher than the group without ischemia. In addition, patients with poor prognostic outcome (GOS score of 1, 2, 3) had significantly higher levels of CC in all three periods than that of patients with good outcome (GOS score of 4, 5). CONCLUSION: The raised CSF CC concentrations appear to be associated with the severity of bleeding, intraoperative ischemic events and poor prognostic outcome in patients with aneurysmal SAH.

Magnesium excretion and hypomagnesemia in pediatric renal transplant recipients.

BACKGROUND: We investigated magnesium excretion and rate of hypomagnesemia in pediatric renal transplant recipients. METHOD: The medical records of 114 pediatric renal transplant recipients were retrospectively evaluated. After exclusion of 23 patients, 91 patients were included in the study. We recorded serum magnesium levels at the time of measurement of urine magnesium wasting. RESULTS: Mean serum magnesium levels were 1.73 ± 0.22 mg/dL and 38 of the patients (41%) had hypomagnesemia. There was a negative correlation between serum magnesium levels and estimated glomerular filtration rate and serum tacrolimus trough level (r=-0.215, p=0.040 and r=-0.409, p=0.000, respectively). Also, there was a statistically significant positive correlation between serum magnesium levels and transplantation duration (r=0.249, p=0.017). Mean fractional magnesium excretion was 5.9 ± 3.7% and 59 patients (65%) had high magnesium excretion. There was a significant negative correlation between fractional magnesium excretion and estimated glomerular filtration rate (r=-0.432, p=0.001). There was a significant positive correlation between fractional magnesium excretion and serum creatinine (r=0.379 p=0.003). CONCLUSION: Patients with higher tacrolimus trough blood levels, lower glomerular filtration rate and at early posttransplant period had risk of hypomagnesemia.

Clinical value of cystatin C and beta-trace protein in glomerular filtration rate in renal transplant cases with stable renal graft functions: comparison by the 99mTc-DTPA plasma sample method.

AIM: The aim of this study was to investigate the value of cystatin C and beta-trace protein (BTP) levels in determination of the glomerular filtration rate (GFR) by accepting the technetium-99m diethylenetriamine pentaacetic acid (Tc-DTPA) method as the gold standard for GFR measurement in renal transplant patients with stable renal functions and to investigate the value of cystatin C and BTP levels in the determination of GFR in cases with or without renal tubular injury. METHODS: A total of 89 (60 men and 29 women) renal transplant patients aged 19-67 years (mean 38.15 years) with stable graft functions were included in the study. GFR was calculated using three different methods: (a) the Tc-DTPA two plasma sample method; (b) eight different formulas containing cystatin C; and (c) three different formulas containing BTP. In addition, the cases were divided into two groups on the basis of N-acetyl-ß-D-glucosaminidase and ß2 microglobulin levels showing tubular damage. RESULTS: GFR values obtained with cystatin C had a better correlation with the gold standard method compared with those obtained with BTP, and the GFR value obtained with cystatin C had the most reliable consistency. We found that cystatin C provided more accurate results in GFR follow-up in renal transplant patients with no tubular injury compared with those with tubular injury. CONCLUSION: Cystatin C is a good marker of GFR in renal transplant patients, especially in those with no tubular injury; however, BTP is not as good as cystatin C in that regard.

[Investigation of hepatitis B and hepatitis C virus infections by serological and molecular methods in hemodialysis patients]. / Hemodiyaliz hastalarinda hepatit B ve hepatit C virus enfeksiyonlarinin serolojik ve moleküler yöntemlerle arastirilmasi

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are significant causes of morbidity and mortality in hemodialysis patients, since those patients are highly susceptible to infections due to immune suppression. The aims of this study were to investigate the presence of HBV and HCV infections in chronic hemodialysis patients by serological and molecular methods, and to determine the rate of occult HBV infection and the viral genotypes. A total of 201 patients who were under hemodialysis due to end-stage renal disease, were retrospectively evaluated. The study involved the patients at three different centers in Antalya, Turkey during 2006. HBV and HCV markers in the patients' sera were screened by ELISA method, viral nucleic acids were investigated by real-time polymerase chain reaction (PCR) in patients' plasma and viral genotypes were determined by DNA sequence analysis. Detection of at least one of the HBV markers HBsAg, anti-HBc total, and HBV DNA, was accepted as HBV infection, and detection of anti-HCV and/or HCV RNA was accepted as HCV infection. HBsAg positive patients with negative HBV DNA were considered as occult HBV infection. Of the patients 80 (40%) were female, 121 (60%) were male and the mean age was 51.16 ± 16.28 (range 17-93) years. In our study, sole anti-HBs positivity due to HBV vaccination, was detected in 89 (44.3%) patients. One hundred (50%) patients were found positive in terms of HBV infection and 40 (20%) were positive for HCV infection, while 24 (12%) patients had HBV and HCV co-infections. Eighty-five (42.3%) patients had no HBV and HCV infection. Among the 5 (2.5%) patients who were HBsAg positive, four were also HBV DNA positive. Occult HBV infection was detected in 1 (0.5%) patient. Anti-HCV and HCV RNA were found positive in 37 (18.4%) and in 24 (12%) patients, respectively. Among the HCV-RNA positive patients, 3 (12.5%) were anti-HCV negative. ALT and AST levels were found normal in all of the HBV DNA positive patients, and 62.5% (15/24) of HCV RNA positive patients. All of the HBV isolates were identified as genotype D and HCV isolates as genotype 1b. No statistically significant correlation was detected between the HBV infection and patients' age, duration of hemodialysis and elevation of serum transaminase levels (p> 0.05). On the other hand, HCV infection was seen to increase with age (p= 0.047). HCV infection showed a statistically significant increase with the duration of hemodialysis. HCV infection risk was increased in patients who were under hemodialysis for ≥ 25 months (p< 0.001, OR: 0224, 95% CI= 0089-0562). There was also a statistically significant correlation between the presence of HCV infection (anti-HCV and/or HCV RNA positive) and high levels of serum transaminases (p< 0.001). However, in two of the three cases who were anti-HCV negative and HCV RNA positive, serum transaminase levels were normal while the viral loads were high. Therefore to follow-up HCV infection in the hemodialysis patients, anti-HCV and serum transaminase levels may not be sufficient alone and these patients should be evaluated periodically for HCV RNA. In addition, the detection of occult HBV infection in one of the study patients, indicated that HBV DNA should also be investigated at regular intervals in the hemodialysis patients.

Association between vitamin D deficiency and disease activity in juvenile idiopathic arthritis.

Vitamin D has been shown to have immunomodulatory and anti-inflammatory properties in addition to its well-established role in the maintenance of mineral homeostasis and bone health. The aims of this study were to evaluate vitamin D status in patients with juvenile idiopathic arthritis (JIA), and also to examine whether there is an association between serum levels of 25-hydroxyvitamin D [25(OH)D] and disease activity in JIA. Children with JIA who had an outpatient visit between March and April 2011 were evaluated retrospectively. Clinical and laboratory findings and vitamin D levels were evaluated. Disease activity was calculated using JADAS-27. Serum vitamin D levels were measured using high-performance liquid chromatography (HPLC). A total of 47 patients, 29 (61.7%) of them girls, with a mean age of 9.3±3.9 years and a median follow-up period of 28 months, were included in the study. The mean serum vitamin D level of all patients was 17.7±11.6 ng/ml. Vitamin D insufficiency (serum vitamin D: 15-20 ng/ml) and deficiency (serum vitamin D level <15 ng/ml) were found in 9 (19.1%) and 25 patients (53.2%), respectively. The vitamin D level was <20 ng/ml in 72.3% of the children. Only 13 patients (27.7%) were found to have adequate vitamin D levels (>20 ng/ml). There was a significant negative correlation between vitamin D levels and disease activity (p=0.01, r=-0,37). The mean JADAS-27 score was significantly higher in patients with 25(OH)D levels <15 ng/ml than in patients with 25(OH)D levels >15 ng/ml (p = 0.003). We suggest that vitamin D deficiency may be a possible modifiable risk factor affecting disease activity in JIA.