Follistatin as a Potential Biomarker for Identifying Metabolically Healthy and Unhealthy Obesity: A Cross-Sectional Study.

Metabolically healthy obesity (MHO) refers to obese individuals with a favorable metabolic profile, without severe metabolic abnormalities. This study aimed to investigate the potential of follistatin, a regulator of metabolic balance, as a biomarker to distinguish between metabolically healthy and unhealthy obesity. This cross-sectional study included 30 metabolically healthy and 32 metabolically unhealthy individuals with obesity. Blood samples were collected to measure the follistatin levels using an enzyme-linked immunosorbent assay (ELISA). While follistatin did not significantly differentiate between metabolically healthy (median 41.84 [IQR, 37.68 to 80.09]) and unhealthy (median 42.44 [IQR, 39.54 to 82.55]) individuals with obesity (p = 0.642), other biochemical markers, such as HDL cholesterol, triglycerides, C-peptide, and AST, showed significant differences between the two groups. Insulin was the most significant predictor of follistatin levels, with a coefficient of 0.903, followed by C-peptide, which exerted a negative influence at -0.624. Quantile regression analysis revealed nuanced associations between the follistatin levels and metabolic parameters in different quantiles. Although follistatin may not serve as a biomarker for identifying MHO and metabolically unhealthy obesity, understanding the underlying mechanisms that contribute to metabolic dysfunction could provide personalized strategies for managing obesity and preventing associated complications.

A comparative evaluation of low-density lipoprotein cholesterol estimation: Machine learning algorithms versus various equations.

BACKGROUND: Given the critical importance of Low-density lipoprotein cholesterol (LDL-C) levels in determining cardiovascular risk, it is essential to measure LDL-C accurately. Since the Friedewald formula generates incorrect predictions in many circumstances, new equations have been developed to overcome the Friedewald equations' shortcomings. This study aimed to compare estimated LDL-C with directly measured LDL-C (dLDL-C), as well as their performance in predicting LDL-C, utilizing Friedewald, extended Martin-Hopkins, Sampson, de Cordova, and Vujovic formulas and five machine learning (ML) algorithms. METHODS: A total of 29,504 samples from the ISLAB-2 Core Laboratory were included in the study. All statistical analysis was performed using R version 4.1.2. Statistical Language. RESULTS: Bayesian-Regularized Neural Network (BRNN) (r = 0.957) and Random Forest (RF) (r = 0.957) algorithms showed a higher correlation with dLDL-C than the other equations in all-testing dataset. All ML algorithms demonstrated less bias than pre-existing LDL-C equations with dLDL-C and outperformed the LDL-C estimation equations in terms of concordance in all-testing dataset. CONCLUSIONS: The results of our research indicate that when compared to conventional equations, ML algorithms are much more effective in predicting LDL-C. ML algorithms, aided by a vast dataset, could have the capability to predict LDL-C levels even in cases where triglyceride levels are high, unlike the limited usage of Friedewald formula.

Role of serum levels of tumour necrosis factor-like weak inducer of apoptosis (TWEAK) in predicting severity of acute appendicitis.

Objectives: One of the most prevalent abdominal crises is acute appendicitis (AA). Clinical diagnosis, even for skilled surgeons, is frequently challenging, as indicated by the high proportion of negative investigations. The purpose of this study was to see if serum TWEAK levels might be used to diagnose acute appendicitis. Material and Methods: Between June 2017 and May 2019, all patients who had surgery with the original diagnosis of AA were included in the study. TWEAK, WBC, CRP, and bilirubin levels were compared. Results: The levels of WBC, CRP, and bilirubin were compared to pathology. All three blood indicators increased significantly in AA patients. However, no statistically significant difference in the levels of all three blood indicators was seen between individuals with simple AA and those with severe AA. TWEAK plasma concentrations were considerably greater in patients with severe AA than in the healthy control and NAA groups. TWEAK levels were significantly greater in individuals with severe AA compared to patients with simple AA. Conclusion: Serum TWEAK levels that are elevated may be used to diagnose acute appendicitis as well as prognostic indicators for the severity of appendicitis.

The Relationship Between Lymphocyte Subtypes with Clinicopathological Features and Prognosis of Prostate Cancer in Patients Undergoing Radical Prostatectomy.

OBJECTIVE: The immune system has an essential role in the development of cancer by showing both anti-tumor and pro-tumor activities. Understanding the immune func- tion of patients with malignancy is of clinical importance for the evaluation, treatment, and prognosis of the disease. We aimed to evaluate lymphocyte subtypes in peripheral blood samples of prostate cancer patients and their relationship with clinicopathologi- cal features and prognosis. METHODS: One hundred thirty-seven patients who underwent open radical prosta- tectomy were included in our study. The percentages of CD3+T lymphocyte, CD19+ B lymphocyte, CD16/56 natural killer cells, CD4+ helper T lymphocyte, CD8+ cytotoxic T lymphocyte, and CD45 total lymphocyte were evaluated for each patient using the blood sample taken into a hemogram tube before surgery. RESULTS: The pathological stage was T2 for 64 of the cases and T3 for 73. The mean follow-up period of the patients was 12.81 ± 6.20 months. The CD3+/CD4+ counts of the patients with pathological stage T2 were found to be statistically significantly higher than stage T3. There was a statistically significant negative correlation between the prostate-specific antigen levels and CD3+/CD4+ percentages of the patients. There was no statistical significance between the percentages of lymphocyte subtypes and the presence of surgical margin, biochemical recurrence, adjuvant therapy, and cancer upgrade. CONCLUSION: We consider that the increase in the pathological stage and prostate-spe- cific antigen value and the decrease in the number of CD4+ T lymphocyte subtypes may be prognostic markers in prostate cancer patients.

Immunogenicity, safety and clinical outcomes of the SARS-CoV-2 BNT162b2 vaccine in adolescents with type 1 diabetes.

Introduction: The mRNA-based BNT162b2 (Pfizer-BioNTech) vaccine has been shown to elicit robust systemic immune response and confer substantial protection against the severe coronavirus disease (COVID-19), with a favorable safety profile in adolescents. However, no data exist regarding immunogenicity, reactogenicity and clinical outcomes of COVID-19 vaccines in adolescents with type 1 diabetes (T1D). In this prospective observational cohort study, we examined the humoral immune responses and side effects induced by the BNT162b2 vaccine, as well as, the rate and symptomatology of laboratory-confirmed COVID-19 vaccine breakthrough infections after completion of dual-dose BNT162b2 vaccination in adolescents with T1D and compared their data with those of healthy control adolescents. The new data obtained after the vaccination of adolescents with T1D could guide their further COVID-19 vaccination schedule. Methods: A total of 132 adolescents with T1D and 71 controls were enrolled in the study, of whom 81 COVID-19 infection-naive adolescents with T1D (patient group) and 40 COVID-19 infection-naive controls (control group) were eligible for the final analysis. The response of participants to the BNT162b2 vaccine was assessed by measuring their serum IgG antibodies to the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 4-6 weeks after the receipt of first and second vaccine doses. Data about the adverse events of the vaccine was collected after the receipt of each vaccine dose. The rate of COVID-19 vaccine breakthrough infections was evaluated in the 6-month period following second vaccination. Results: After vaccinations, adolescents with T1D and controls exhibited similar, highly robust increments in anti-SARS-CoV-2 IgG titers. All the participants in the patient and control groups developed anti-SARS-CoV-2 IgG titers over 1,050 AU/ml after the second vaccine dose which is associated with a neutralizing effect. None of the participants experienced severe adverse events. The rate of breakthrough infections in the patient group was similar to that in the control group. Clinical symptomatology was mild in all cases. Conclusion: Our findings suggest that two-dose BNT162b2 vaccine administered to adolescents with T1D elicits robust humoral immune response, with a favorable safety profile and can provide protection against severe SARS-CoV-2 infection similar to that in healthy adolescents.

Association of Low Levels of Soluble Low-Density Lipoprotein Receptor-Related Protein-1 and COVID-19 Outcomes During the First Wave of Pandemic.

Low-density lipoprotein receptor-related protein-1 (LRP1) is an endocytosis receptor that clears inflammatory proteins from circulation. LRP1 has anti-inflammatory effects that bind pro-inflammatory cytokines or ligands. LRP1 has a soluble form (sLRP1) which can be measured in serum. We report sLRP1 levels in hospitalized patients with COVID-19. The first objective of this study is to compare the sLRP1 levels between COVID-19 patients and healthy controls. The second objective is to examine the association between sLRP1 and the clinical outcome of COVID-19. All patients (20-80 years of age) were evaluated in a hospital using a positive PCR test for SARS­CoV­2 between April 1, 2020, and June 1, 2020. Controls (n=59) were selected from healthy subjects. sLRP1 levels were measured in patients from the emergency department (ED), inpatient service (IS), and the intensive care unit (ICU). The study included 180 cases. COVID-19 patients showed significantly lower sLRP1 levels compared to controls (1.43 (1.86) versus 2.27 (1.68) µg/mL, respectively, p<0.001). sLRP1 levels were 1.26 (1.81), 1.37 (1.65), and 1.74 (1.98) µg/mL in patients from ED, IS, and ICU, respectively (p=0.022). Patients who were admitted from ED displayed lower sLRP1 levels compared to those who were discharged (median sLRP1 levels were 0.86 versus 1.7 µg/mL, p=0.045). COVID-19 patients display significantly lower sLRP1 levels compared to the healthy controls. sLRP1 levels do not show any association with the clinical outcome of COVID-19. This study demonstrates that LRP1 displays a bidirectional course in COVID-19. A low sLRP1 level is a potential risk factor for susceptibility and hospital admission due to COVID-19. Further studies with larger sample sizes and longer follow-ups are needed to understand the long-term effects of novel biomarkers such as sLRP1 on the outcome of COVID-19.

Adaptive immune system in severe COVID-19 patients in the first week of illness: A pilot study.

Introduction: The presentation of the course of COVID-19-related T-cell responses in the first week of the disease may be a more specific period for adaptive immune response assessment. This study aimed to clarify the relationship between changes in peripheral blood lymphocyte counts and death in patients with COVID-19 pneumonia. Methods: Thirty-three patients (14 females and 19 males) admitted for severe and desaturated COVID-19 pneumonia confirmed by polymerase chain reaction were included. Lymphocyte subsets and CD4+/CD8+ and CD16+/CD56+ rates were measured using flow cytometry from peripheral blood at admission and on the day of death or hospital discharge. Results: Twenty-eight patients survived and five died. On the day of admission, the CD4+ cell count was significantly higher and the saturation of O2 was significantly lower in the deceased patients compared to the survivors (P < 0.05). The CD16+/CD56+ rate was significantly lower on the day of death in the deceased patients than in discharge day for the survivors (P = 0.013). Conclusion: CD4+ lymphocyte percentages and O2 saturation in samples taken on the day of admission to the hospital and CD16+/CD56+ ratios taken at the time of discharge from the hospital were found to be associated with the mortality in patients with severe COVID-19.

Soluble low density lipoprotein receptor-related protein-1 levels in the differential diagnosis of myopericarditis versus acute coronary syndrome.

INTRODUCTION: Differential diagnosis of myopericarditis (MPC) versus acute coronary syndromes (ACS) can be difficult in the emergency room (ER). Low density lipoprotein receptor-related protein-1 (LRP-1) is a transmembrane receptor with diverse biological functions. LRP-1 is increased after viral infections as a defense mechanism. sLRP-1 (soluble form) can be measured in the serum. We study the diagnostic sLRP-1 levels in patients with MPC, ACS and healthy controls. METHODS: The study included consecutive patients who were admitted between the dates of 1.1.2018 and 1.1.2019 with the diagnosis of MPC or ACS. All patients reported to the ER with chest pain (CP) and elevated cardiac troponin levels. Control group (n = 61) was selected from healthy subjects. In addition to routine laboratory work up, serum sLRP-1 concentrations were measured on admission. RESULTS: sLRP-1 levels were significantly higher in MPC, compared to controls (p = 0.005) and ACS (p = 0.001). Median (IQR) sLRP-1 levels in MPC, controls and ACS were 7.39 (22.42), 2.27 (1.74), 2.41 (0.98) µg/ml, respectively (p = 0.004). Among the covariates: sLRP-1, age, gender, HDL-C and LDL-C; only sLRP-1 differentiated a diagnosis of MPC versus ACS (OR = 1684, p = 0,046, CI for OR (1008-2812). The area under the curve (AUC) was measured as 0.79 [CI 0.62-0.95] in ROC analysis, p = 0.001; sLRP-1 had 69% sensitivity and 85% specificity for diagnosis of MPC with a cut-off value of 4.3 µg/ml. CONCLUSION: sLRP-1 is a potential biomarker in the differential diagnosis of MPC versus ACS in ER. Future studies are needed to evaluate and develop the utility of sLRP-1 as a diagnostic and prognostic biomarker in MPC.

Low levels of soluble low-density lipoprotein receptor-related protein 1 in patients with type 2 diabetes mellitus and diabetic retinopathy.

Low-density lipoprotein receptor-related protein-1 (LRP-1) is a large transmembrane receptor. LRP-1 plays a role in diverse cellular processes, including lipid metabolism, cell growth, migration, and regeneration. Soluble form of LRP-1 (sLRP-1) can be detected in serum. sLRP-1 can serve as a biomarker of atherosclerosis and cardiometabolic diseases. This study investigated the concentrations of the circulating serum sLRP-1 in patients with retinopathy and type 2 diabetes mellitus. Fifty-two patients with diabetic retinopathy and 71 controls were enrolled based on well-defined eligibility criteria. Venous blood samples were collected after 12 h of fasting. sLRP-1 concentrations were measured using the commercially available ELISA in an accredited laboratory. The mean age of patients and control groups were 63.6 and 48.5 years, respectively. The median disease duration was 8.1 years. The median serum sLRP-1 levels were lower in patients with diabetic retinopathy compared to the controls (2.11 µg/mL versus 2.44 µg/mL, p = 0.034). No significant correlation was observed between the sLRP-1 and serum lipid levels. The sLRP-1 levels are low in patients with diabetic retinopathy compared to healthy controls, and future studies are needed to assess sLRP-1 as a potential biomarker in diabetic retinopathy.

Protective effect of liraglutide on experimental testicular ischaemia reperfusion in rats.

This study was performed to evaluate the effect of liraglutide on experimental testicular ischaemia reperfusion in rats in terms of biochemistry, histopathology and immunohistochemistry. A total of 28 male Wistar-Albino rats were divided randomly into 4 groups: control (7), sham (7), ischaemia-reperfusion (7) and ischaemia-reperfusion + liraglutide (7). Biochemically, Nitric Oxide, Malondialdehyde, Superoxide dismutase, Glutathione peroxidase and Catalase levels were measured in the testis. Apoptosis protease activating factor-1 and inducible nitric oxide synthase activity were evaluated immunohistochemically as well. Statistical analyses were made via the Kruskal-Wallis and Mann-Whitney U tests. In the reperfusion group, CAT and SOD values were increased (p > .05), NO and MDA values were decreased (p < .05) after administration of liraglutide. In addition, GPx values were significantly increased in ischaemia reperfusion + liraglutide administered group compared to reperfusion group (p < .05). Apaf-1 and iNOS activity were significantly decreased with the addition of liraglutide treatment to the ischaemia-reperfusion group (p < .05). First of all, we would like to say that liraglutide treatment is moderately preventive against I/R injury in testicular torsion. The anti-inflammatory, antioxidant and antiapoptotic properties of liraglutide are create a moderately protective effect as we show in this study.

The effects of shock wave lithotripsy and retrograde intrarenal surgery on renal function.

INTRODUCTION: The aim of this study was to compare the early effects of shock wave lithotripsy (SWL) and retrograde intrarenal surgery (RIRS) on renal function using the cystatin C levels. MATERIAL AND METHODS: Serum samples were taken from each of the patients preoperatively, on the first postoperative day, and on the 30th postoperative day in order to evaluate the renal damage. The cystatin C level was determined using a particle-enhanced turbid metric immunoassay with a clinical chemistry analyzer. RESULTS: In the comparison between the preoperative and postoperative cystatin C levels on day 1, there was an increase in the SWL group (p = .001); however, the decrease in the RIRS group was statistically significant (p = .007). There were statistically significant differences in the cystatin C levels on the first postoperative day in both groups (p = .001). In the SWL group, there was a statistically significant increase between the preoperative and the 30th postoperative day cystatin C levels (p = .006), but no differences were found between these levels in the RIRS group or between the two groups (p = .255). CONCLUSIONS: RIRS may be the preferred procedure for patients who need more renal function protection when treating renal stones <2 cm.

Serum levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in predicting the severity of acute pancreatitis.

INTRODUCTION: Acute pancreatitis (AP) is a severe disease associated with significant morbidity and mortality. The overall outcome has improved, but specific treatment(s) remains elusive. The challenge is the early identification and treatment of patients who will develop severe acute pancreatitis. Therefore, the aim of the present study is to investigate plasma levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the initial phase of predicted severe acute pancreatitis. METHODS: Between June 2014 and January 2016, 64 patients with acute pancreatitis and 36 healthy individuals were included to study. Four blood samples, for serum TWEAK measurement, were taken from each individual in each group. The first measurement was taken from the admission blood sample. The subsequent three samples were taken at 12, 24, and 48 h after the hospital admission. RESULTS: Serum TWEAK levels were significantly higher in patients with acute pancreatitis when compared with healthy controls. TWEAK plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients. CONCLUSION: Serum TWEAK levels increase progressively with the severity of acute pancreatitis and TWEAK might be a novel early marker of severity in acute pancreatitis.

Comparative Performance Analysis of Urised 3 and DIRUI FUS-200 Automated Urine Sediment Analyzers and Manual Microscopic Method.

OBJECTIVE: Microscopic examination of urine sediment is necessary for evaluation of renal and urinary tract diseases. In this study, we evaluated and compared analytic and diagnostic performances of DIRUI FUS-200 and a new image-based automated urine sediment analyzer Urised 3. METHOD: A total of 440 urine samples, submitted to our laboratory, were evaluated by two automated urine sediment analyzers and a standardized manual microscopy. Precision, linearity and method comparison studies were performed according to CLSI guidelines. RESULTS: Considering the red blood cell (RBC) and white blood cell (WBC) counts, strong correlations existed between FUS-200 and manual microscopy (r=0.993 vs 0.861), Urised 3 and manual microscopy (r=0.962 vs 0.818), FUS200 and Urised 3 (r=0.961 vs 0.961). Clinical non-concordance ranged from 7% to 14.16% among all methods. CONCLUSIONS: The concordance between the analyzers and manual microscopy for WBC was better than that of RBC. The concordance between the two analyzers was better for WBC and RBC, with respect to the manual microscopy. Although the Urised 3, FUS-200 and manual microscopy counts were in agreement; confirmation of the results of automated analyzers with manual microscopy is particularly helpful, for pathological samples with near cut-off values.

Value of Urinary Brain-Derived Neurotrophic Factor Levels on the Assessment of Botulinum Toxin Type A Treatment for Neurogenic Detrusor Overactivity in Children with Myelodysplasia.

PURPOSE: Urinary cytokines are proposed to predict urodynamic findings and outcome of intradetrusor botulinum neurotoxin type A injection in children with myelodysplasia. The relationship between urinary brain-derived neurotrophic factor and neurogenic and nonneurogenic detrusor overactivity has been shown as well. We prospectively investigated the effect of intradetrusor botulinum neurotoxin type A injection on urine brain-derived neurotrophic factor levels in children with nonneurogenic detrusor overactivity due to myelodysplasia. MATERIALS AND METHODS: Urine samples of 23 children with nonneurogenic detrusor overactivity due to myelodysplasia were collected and analyzed before and 1 and 3 months after intradetrusor botulinum neurotoxin type A injection, and urodynamics were performed before and 6 weeks after injection. Brain-derived neurotrophic factor levels and urodynamic findings were analyzed and statistical comparisons were done. RESULTS: Mean ± SD age was 100.0 ± 34.5 months. Ratio of girls to boys was 2.8. Brain-derived neurotrophic factor levels significantly decreased (p <0.006), and maximum cystometric capacity and maximum detrusor pressure improved significantly following intradetrusor botulinum neurotoxin type A injection compared to preoperatively (p <0.001). No statistical correlations were determined between brain-derived neurotrophic factor levels and urodynamics. Of all analyses only bladder compliance 5 ml/cm H2O or less vs greater than 5 ml/cm H2O at postoperative urodynamics was associated with statistically increased urine brain-derived neurotrophic factor levels, suggesting that increased urine brain-derived neurotrophic factor predicts treatment failure. CONCLUSIONS: The present study does not suggest that urine brain-derived neurotrophic factor is a reliable followup marker in children with nonneurogenic detrusor overactivity due to myelodysplasia. However, this factor may have a role in treatment planning, which needs to be established in future large prospective studies.

The effect of intradetrusor botulinum neurotoxin type A on urinary NGF, TGF BETA-1, TIMP-2 levels in children with neurogenic detrusor overactivity due to myelodysplasia.

AIMS: The aim of this study was to determine the value of urine nerve growth factor (NGF), transforming growth factor beta 1 (TGF-Beta-1), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) levels to predict the urodynamic profile before and after botulinum neurotoxin type A (BoNT-A) treatment in children with myelodysplasia. METHODS: This prospective study included 15 children with myelodysplasia who underwent intradetrusor BoNT-A injections due to neurogenic detrusor overactivity (NDOA). Urine samples of each child were collected before and after BoNT-A injections, specifically at the first and third postoperative months. Urine samples were analyzed with ELISA method and NGF, TGF-Beta-1, and TIMP-2 levels were measured. Urine marker levels and clinical findings were assessed for statistical significance with Wilcoxon Signed Ranks Test and Friedman Test. RESULTS: A total of 15 children (5 boys and 10 girls) were assigned as the study group. Mean age of the patients was 7.1 ± 2.5 years (range 2.5-11). A statistically significantly decline was observed in urinary TGF-Beta-1 and NGF levels following BoNT-A injections, compared to the preoperative levels (P < 0.05). TIMP-2 levels also tend to decrease following BoNT-A injections but this was not statistically significant compared to the preoperative levels. CONCLUSION: This preliminary study, suggests urinary TGF-Beta-1 and NGF as a potent marker in children with NDOA, as they decline following BoNT-A injection. Further studies are needed in identifying their special role in assessing treatment success after invasive interventions.

Can Pentraxin-3 be a Candidate Marker in the Follow-Up of the Patients With Behçet's Disease?

OBJECTIVES: This study aims to assess the level of pentraxin-3 (PTX-3) as an inflammatory marker and compare it with C-reactive protein (CRP) levels in patients with Behçet's disease (BD). PATIENTS AND METHODS: Forty-two patients with BD (15 males, 27 females; mean age 39.7±8.6 years; range 20 to 64 years) and 42 age- and sex- matched healthy controls (14 males, 28 females; mean age 40.8±8.2 year; range 25 to 60 years) were included in the study. Serum CRP and plasma PTX-3 levels were measured. Subgroup analyses were performed according to clinical manifestations of patients with BD. RESULTS: Both PTX-3 and CRP levels were significantly higher in patients with BD than controls (1.33±0.29 vs 0.85±0.12, p<0.05 for PTX-3 and 0.71±0.13 vs 0.27±0.03, p<0.001 for CRP, respectively). Area under the curve was 0.633±0.062 vs 0.729±0.05, respectively. Mean PTX-3 and CRP levels were 1.1 vs 1.5, p=0.5; 0.5 vs 0.9, p=0.5; respectively, in patients with mucocutaneous involvement alone and with other involvements, whereas they were 0.9 vs 1.6, p=0.1; 0.5 vs 0.8, p=0.3; respectively, in patients with and without peripheral arthritis, and were 1.7 vs 0.9, p=0.06; 1.0 vs 0.5, p=0.07; respectively, in patients with and without uveitis. CONCLUSION: Although PTX-3 levels were higher in patients with BD than healthy controls, sensitivity and specificity of PTX-3 was not different than CRP in patients with BD.

Fibroblast growth factor-23 but not sKlotho levels are related to diastolic dysfunction in type 1 diabetic patients with early diabetic nephropathy.

PURPOSE: To investigate the soluble Klotho (sKlotho) and fibroblast growth factor-23 (FGF-23) levels and echocardiographic findings in type 1 diabetic patients with no or early diabetic nephropathy. METHODS: A total of 147 subjects (mean age 34.1 ± 9.2 years, 55.8 % were females) including type 1 diabetic patients with glomerular filtration rate (GFR) >60 ml/min (n = 71, mean age 34.3 ± 9.5 years, 54.9 % were females) and healthy controls (n = 76, mean age 33.9 ± 9.1 years, 56.6 % were females) were included in this study. Data on demographic characteristics, blood biochemistry, urinalysis, diabetes-related complications and echocardiography were recorded. Serum levels for sKlotho and FGF-23 were determined by ELISA method. RESULTS: Patient and control groups were similar in terms of mean sKlotho (509.2 ± 183.5 and 547.6 ± 424.0 pg/ml, respectively) and FGF-23 (76.2 ± 15.6 and 77.2 ± 15.1 pg/ml, respectively) levels as well as echocardiographic findings. No significant correlation of sKlotho (pg/ml) and FGF-23 (pg/ml) levels with cardiac parameters was noted among diabetic patients. In subgroup analysis, the correlations between FGF-23 levels and isovolumic relaxation time (ms) and early diastolic velocity at medial/septal annulus (E'med) (m/s) were significant only in patients with early diabetic nephropathy (DN) but not in non-DN patients. No significant association of sKlotho levels with echocardiographic findings was noted. CONCLUSIONS: Our findings in young adult type 1 diabetic patients with GFR >60 ml/min versus healthy controls revealed no difference between groups in terms of sKlotho and FGF-23 levels and echocardiographic findings, while a significant correlation of FGF-23 (pg/ml) levels and diastolic dysfunction was noted only in patients with DN.

C-reactive protein but not hepcidin, NGAL and transferrin determines the ESA resistance in hemodialysis patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESA) are commonly used for the treatment of anemia in hemodialysis (HD) patients, however, 5-10% of these patients have resistance to ESA treatment. Hepcidin and neutrophil-gelatinase associated lipocalin (NGAL) are induced by inflammation and these proteins may take role in ESA resistance. Herein, we aimed to investigate the effects of serum hepcidin, NGAL, transferrin and C-reactive protein (CRP) levels on ESA resistance in HD patients. METHODS: A total of 63 chronic HD patients (6.0 ± 17 years, M/F:44/19) and 20 healthy controls (6.0 ± 4 years, M/F:14/6) were enrolled. ESA resistance index (ERI) was calculated as weekly ESA dose (IU)/body weight (kg)/hemoglobin level (g/dL). Patients on ESA treatment were divided into two groups depending on the median ERI value as low and high ERI groups. RESULTS: Serum ferritin, hepcidin and NGAL levels were significantly higher in HD patients compared with controls. Serum transferrin levels were lower in high ESA index group compared with patients without ESA treatment and healthy controls. ERI was significantly correlated with serum CRP levels (r = 0.55, p < 0.001). In HD patients, serum hepcidin levels were associated with ferritin (r = 0.55, p < 0.01) and creatinine (r = 0.27, p = 0.03). Dose of ESA was significantly associated with serum CRP (r = 0.34, p = 0.02), total protein (r = -0.34, p = 0.01), transferrin (r = -0.28, p = 0.04) and ferritin (r = 0.31, p = 0.02). In linear regression analysis to predict ERI, age, gender, serum CRP, hepcidin, NGAL, albumin, ferritin and BMI were included (Model R = 0.62, R(2) =0 .38, p = 0.02). Serum CRP was the only significant factor predicting ERI. CONCLUSION: CRP was the only predictor of ESA resistance index in HD patients. Hepcidin, NGAL and transferrin were not found to be markers of ESA resistance.

Urinary kidney injury molecule-1 levels as a marker of early kidney injury in hypertensive patients.

BACKGROUND: Kidney injury molecule-1 (KIM-1) is a type 1 tubular cell transmembrane protein that is found in high levels in early stages of acute kidney injury and is stated to have predictive value in the early diagnosis of chronic kidney diseases. In this study, the hypothesis was that higher levels of KIM-1 would be detected in hypertensive patients for the early detection of nephropathy. With this goal, urinary KIM-1 levels of hypertensive cases were compared with those of healthy controls, and associations of KIM-1 levels with microalbuminuria and glomerular filtration rate (GFR) were investigated. METHODS: The study included a total of 80 patients aged ≥20 years (55 male, 25 female, mean age: 57.21±9.12 years). The patient group consisted of 40 patients (28 males, 12 females, mean age: 57.58±8.79 years) who had had hypertension for at least 5 years, and the control group consisted of 40 healthy subjects (27 female, 13 male, mean age: 56.85±9.53 years). Groups were compared based on demographic, anthropometric and biochemical data, and urinary KIM-1 levels. Correlation analysis was made to assess the association of KIM-1 levels with microalbuminuria and GFR. Levels of urinary KIM-1 enzyme were measured using linked immunosorbent assay (ELISA). RESULTS: KIM-1 levels were found to be 0.86±0.48 ng/mg creatinine in the patient, and 0.71±0.46 pg/mL in the control groups (P>0.05). A positive correlation was detected between KIM-1 levels and both systolic blood pressure and duration of disease (r=0.308, P=0.032 and r=0.339, P=0.032, respectively). CONCLUSIONS: While not supporting the hypothesis that KIM-1 levels may increase in hypertensive patients as an early indicator of hypertensive nephropathy, these findings suggested that this molecule might be associated with kidney injury in hypertensive nephropathy due to its positive correlation with the duration of hypertension.

Urinary NGF, TGF-ß1, TIMP-2 and bladder wall thickness predict neurourological findings in children with myelodysplasia.

PURPOSE: Dimercapto-succinic acid scintigraphy and urodynamic studies are gold standards to evaluate renal scarring and neurogenic bladder dysfunction, respectively. We sought to establish the value of bladder wall thickness together with urine NGF, TGF-ß1 and TIMP-2 to predict the urodynamic profile and upper urinary tract damage in children with myelodysplasia. MATERIALS AND METHODS: A total of 80 children with myelodysplasia underwent urodynamic investigation, bladder wall thickness measurement and dimercapto-succinic acid scintigraphy with basic neurourological evaluation. Two study and 2 control groups were created according to presence or absence of renal scarring on dimercapto-succinic acid scan (study and control groups 1) and according to detrusor leak point pressure greater or less than 40 cm H2O (study and control groups 2). Urine samples were analyzed with ELISA. RESULTS: The study population consisted of 44 girls and 36 boys with a median ± SD age of 7.2 ± 3.6 years (range 2 to 17). Study and control groups 1 consisted of 35 and 45 children with abnormal and normal dimercapto-succinic acid scan findings, respectively. Study and control groups 2 included 30 and 50 children with detrusor leak point pressure greater and less than 40 cm H2O, respectively. Bladder wall thickness and urinary levels of TGF-ß1, NGF and TIMP-2 were significantly increased in both study groups compared to controls. CONCLUSIONS: Urine markers and bladder wall thickness measurement may predict urinary tract impairment in children with myelodysplasia. Such markers may differentiate at risk patients with either renal scarring or high detrusor leak point pressure, and decrease the need for urodynamics and renal scintigraphy.