Value of Cystatin C-Based e-GFR Measurements to Predict Long-Term Tenofovir Nephrotoxicity in Patients With Hepatitis B.

BACKGROUND: Cystatin C is a genuine marker for detecting minor reductions in estimated glomerular filtration rate (e-GFR). STUDY QUESTION: We aimed to investigate the efficiency of cystatin C levels in predicting nephrotoxicity due to antiviral therapy in patients with chronic hepatitis B virus infection. STUDY DESIGN: Seventy-six naive hepatitis B virus patients and 44 controls were enrolled in this prospective cohort study. MEASURES AND OUTCOMES: Serum cystatin C, phosphate and creatinine levels, and urinary albumin/creatinine ratios of all patients were measured at baseline, 3rd, 12th, and 24th months. Nephrotoxicity was determined according to the amount of change in creatinine level at the fourth year of treatment compared with baseline ([INCREMENT]Cr0-4). RESULTS: Mean age was 36.1 ± 9.2 years and 40 (52.2%) of patients were women. There was no significant difference between baseline values of tenofovir disoproxil fumarate and entecavir groups. Although the creatinine level at the fourth year of treatment was statistically nonsignificant compared with baseline in the entecavir group, it was significantly higher in the fourth year of tenofovir treatment compared with baseline (0.95 ± 0.27 mg/dL vs. 0.76 ± 0.16 mg/dL, P = 0.002). While the increase in [INCREMENT]Cr0-4 was ≥0.2 mg/dL in 43.2% of patients in the tenofovir group, this rate was 18.8% in the entecavir group. Diagnostic accuracy in identifying decreased renal function as area under the curve (AUC) was high for baseline serum cystatin C level; furthermore, the highest AUC was calculated for cystatin C plus creatinine-based e-GFR equation (AUC: 0.81, P < 0.001). CONCLUSIONS: Long-term tenofovir disoproxil fumarate nephrotoxicity can be predicted by serum cystatin C plus creatinine-based e-GFR measured before treatment.

Importance of evaluation of heart-type fatty acid binding protein (H-FABP) in COVID-19 Patients.

INTRODUCTION: Recent studies have documented the cardiovascular consequences of acute coronavirus disease 2019 (COVID-19), although one of the early cardiac markers that can be used for diagnosis, the heart-type fatty acid-binding protein (H-FABP), has not been covered. Through the evaluation of H-FABP levels, we aim to contribute to the early diagnosis and treatment of cardiac problems in COVID-19 infection patients. METHODOLOGY: Seventy-five patients who were admitted to the emergency department of Mehmet Akif Ersoy Hospital with a complaint of chest pain in the last 6 hours and whose corona PCR tests were positive, were included in our study as the case group and 60 healthy volunteers as the control group. The routine cardiac markers such as creatine kinase MB (CK-MB) cardiac troponin T (cTnT), and H-FABP levels were analyzed by routine laboratory methods. RESULTS: The mean age and gender distributions of the groups did not differ statistically (p > 0.05). CK-MB, cTnT, and H-FABP measurements were statistically different between the groups (p = 0.001; p < 0.01). CONCLUSIONS: The relationship between AMI and COVID-19 with routine cardiac markers is already supported by recent studies. We also evaluated H-FABP levels in our study, as it affects the prognosis of the disease independent of the chronic disease history. At the same time, we showed that H-FABP levels increase earlier than routine cardiac markers, so it will be useful for COVID-19 patients with cardiac complaints.

Evaluation of Ischemic Modified Albumin Levels in Coronavirus Disease 2019-Positive and -Negative Patients with Acute Cardiac Injury.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 is the source of the global pandemic known as coronavirus disease 2019, and the disease prognosis is also linked to the prevalence of cardiac problems. In our study, we aimed to contribute to the early diagnosis and treatment of cardiac complications by evaluating ischemic modified albumin levels in adults with coronavirus disease 2019 disease. METHODS: Our study was conducted with a total of 176 cases: group 1 (n = 70) with cardiac injury and coronavirus disease 2019 (+), group 2 (n = 57) with cardiac injury and coronavirus disease (-), and group 3 (n = 49) with healthy volunteers. The Mann-Whitney U test, the average, SD, minimum and maximum values, intergroup comparison of the results, and statistical significance were evaluated with the Pearson correlation coefficient. RESULTS: As a result of the bilateral comparisons, ischemic modified albumin measurements of the coronavirus disease 2019 (+) and coronavirus disease 2019 (-) groups were higher than the control group (P =.006 and P =.006, respectively). There was no statistically significant difference between ischemic modified albumin measurements of coronavirus disease 2019 (+) and coronavirus disease 2019 (-) groups. CONCLUSION: Ischemic modified albumin measurement accelerates the diagnosis and treatment process in the evaluation of cardiac injuries in coronavirus disease 2019 patients.

Evaluation of renal function in rats with moderate and mild brain trauma.

BACKGROUND: We aimed to diagnose possible acute kidney injury (AKI) with new early biochemical markers in patients who were admitted to the emergency department frequently with mild and moderate brain trauma, and to prevent possible complications, shorten the duration of treatment and hospital stay. With this purpose, we decided to reach our scientific target using the experimental rat model. METHODS: Wistar albino rats were included our experiment. Fifteen rats were randomly separated into three groups: Sham control (n=1: Underwent craniotomy alone), control (n=7: Without craniotomy), and trauma group (n=7: Underwent craniotomy followed by brain injury). RESULTS: There were no significant differences groups creatinine levels within 0 and 24 h (0.35±0.02 and 0.33±0.03, respectively, p>0.05). Plasma NGAL and KIM1 concentrations were statistically significant different in both control and trauma groups (Friedman p<0.05) and significant differences at both NGAL and KIM-1 concentrations at dual comparisons by means of all sampling time (0-2 h, 0-24 h, and 2-24 h) (Wilcoxon p<0.001, after Bonferroni correction). CONCLUSION: The presence of AKI in patients with mild-to-moderate brain trauma increases the risk of mortality. Early diagnosis of AKI reduces the hospitalization period and requiring of dialysis. Diagnosis of AKI within 24 h with early biomarkers and starting therapy is crucial issues.

Evaluation of rat major celluler prion protein for early diagnosis in experimental rat brain trauma model.

BACKGROUND: Although traumatic brain injury (TBI) is an important problem, there has been no widespread utilization of neuro-biomarkers to aid the diagnosis of TBI. This study was conducted to evaluate serum S100B and prion protein (PrPC) levels in rats with TBI. METHODS: In this study, 15 albino rats were categorized into three groups as follows: sham-operated (1), control (6) and trauma (8) groups. The TBI model was based on the modified free falling model. S100B, PrPC levels were measured using ELISA. Brain specimens were obtained for the pathological examination. RESULTS: Serum S100B and PrPC levels were found to increase in T group at both 2h and 24h after trauma (p<0.002, p<0.002, respectively). We also found higher histopathological injury scores of brain tissues in the T group. Only a positive correlation was found between serum PrPC levels and the extent of brain injury (p=0.039, r=0.731). Using ROC analysis, among the two serum markers investigated, both of them revealed the same sensitivity and specificity for diagnosing TBI. CONCLUSION: The changes in serum S100B and PrPC levels showed good sensitivity in our experimental model. Therefore, PrPC could be helpful in the early prognostic prediction in patients with TBI. Further studies are needed to test our findings in humans following TBI (penetrating bodies, blunt trauma) to definitively acknowledge it as a reliable biomarker and its subsequent diagnostic utility.

Is there any relation between connective tissue growth factor and scar tissue in vesicoureteral reflux?

Gültekin ND, Benzer M, Tekin-Neijmann S. Is there any relation between connective tissue growth factor and scar tissue in vesicoureteral reflux. Turk J Pediatr 2019; 61: 71-78. Vesicoureteral reflux (VUR) is the most common uropathy in childhood which leads to increased frequency of urinary tract infection (UTI) and renal scarring. Connective tissue growth factor (CTGF) plays an important role in the development of glomerular and tubulointerstitial fibrosis in progressive kidney diseases. The aim of this study was to investigate the relation between urinary CTGF and renal damage resulted from VUR. This cross sectional study included 70 patients with VUR and 62 healthy sex and age matched children. Urinary creatinine and CTGF (uCTGF) concentrations were analysed in all cases and CTGF to creatinine ratio were calculated. The records of radiologic evaluations of the patients including ultrasound, voiding cystouretrography and 99m-technetium dimercaptosuccinic acid (DMSA) scintigraphy were obtained retrospectively. The patient group was further divided into two groups according to the existence of renal cortical scarring in the DMSA scan. The study consisted of three groups; Group 1 (control group) 62 children, Group 2 (VUR positive, scar negative) 24 patient, Group 3 (VUR positive, scar positive) 46 patient (VUR+scar). The medians of uCTGF and uCTGF to creatinine ratio of the three groups were significantly different (p < 0.001). Pairwise group comparisons revealed that Group 1 had significantly lower uCTGF level and uCTGF/creatinine ratio, as compared to Groups 2 and 3 (p < 0.001 and p=0.002, respectively). There was no statistically significant difference between Groups 2 and 3 (p=0.052). uCTGF is significantly increased in children with VUR, independent on the presence of renal scarring. Increased uCTGF, even in the absence of the renal scarring, could be interpreted as development and a progression of glomerular and tubulointerstitial fibrosis in vesicoureteral reflux. Further experimental and clinical investigations are required to fully elucidate the mechanism of CTGF in vesicoureteral reflux.

Urinary L-FABP as a marker of vesicoureteral reflux in children: could it also have a protective effect on the kidney?

PURPOSE: Liver-type fatty acid-binding protein is a small cytoplasmic protein which is expressed in the human renal proximal tubular epithelium and synthesized in response to renal tubular injury. The aim of the present study was to investigate the importance of urinary liver-type fatty acid-binding protein levels in children who diagnosed with vesicoureteral reflux. METHODS: Fifty-six patients with vesicoureteral reflux and 51 healthy controls were enrolled to the study. The cases were divided into three groups as follows: group A-the controls, group B-the patients who had renal parenchymal scarring and group C-the patients who had no scarring. Urinary liver-type fatty acid-binding protein was measured by enzyme-linked immunosorbent assay method. Creatinine was measured by modified Jaffe method, protein was measured by turbidimetric method, and urine density was determined by using the "falling drop" procedure. RESULTS: Urinary liver-type fatty acid-binding protein and urinary liver-type fatty acid-binding protein/creatinine levels were significantly higher in the whole patient group than in the controls (p = 0.016, 0.006). Significant differences were also determined by comparing the three groups (p = 0.015, 0.014), and those levels were found as significantly higher in group C. CONCLUSION: Urinary liver-type fatty acid-binding protein was considered to be helpful for the diagnosis of vesicoureteral reflux, and also it might contribute to understand the mechanisms causing scar tissue formation especially for the patients who had vesicoureteral reflux. Further clinical and experimental investigations are required to elucidate in detail the physiology of liver-type fatty acid-binding protein.

Serum ST2 in inflammatory bowel disease: a potential biomarker for disease activity.

ST2, a specific ligand of interleukin 33, was described as a biomarker protein of inflammatory processes and overexpression of ST2 in ulcerative colitis (UC) was shown previously. We aimed to investigate the potential relationship of serum ST2 levels with the clinical, endoscopic and histopathological activity scores in UC and Crohn's disease (CD). Serum ST2 levels were determined in 143 patients with inflammatory bowel disease (IBD) (83 UC and 60 CD), in 50 healthy controls (HC), and in 32 patients with irritable bowel syndrome (IBS). Serum ST2 levels were elevated in IBD (56.8 (41.9-87.2) pg/mL) compared to HC and IBS (30.7 (20.2-54.3), p<0.001 and 39.9 (25.9-68.7) pg/mL, p=0.002, respectively). No significant difference was found between UC (54.2 (41.3-93.0) pg/mL) and CD (63.8 (42.7-88.4) pg/mL) and between IBS and HC. Serum ST2 levels were significantly increased in active UC compared to inactive UC (72.5 (44.1-99.5) vs 40.0 (34.7-51.6) pg/mL, p<0.001) and in active CD in comparison with inactive CD (63.8 (42.7-88.4) vs 48.4 (29.6-56.9) pg/mL, p=0.036). Patients with CD showing fistulizing behavior had significantly higher ST2 levels compared to patients with inflammatory and stricturing CD (p<0.001). Clinical activity scores of patients with UC and CD were correlated with serum ST2 levels (r=0.692, p<0.001 and r=0.242, p=0.043, respectively). Serum ST2 levels showed stepwise increases with the increasing histopathological scores of patients with UC and CD (p<0.001 for both). The present study highlights significant associations between ST2 and IBD presence and activity and demonstrates elevated serum ST2 levels in patients with active CD as a novel finding.

Plasma Pentraxin 3 Differentiates Nonalcoholic Steatohepatitis (NASH) from Non-NASH.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes a variety of histopathological findings ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which can only be differentiated by liver biopsy. There is yet no unique biomarker found to discriminate NASH from simple steatosis.We aimed to investigate the relationship of plasma pentraxin 3 (PTX3) and its main stimulant tumor necrosis factor alpha (TNF-α) with the degree of liver damage in NAFLD. METHODS: Plasma PTX3 and TNF-α levels were measured in 70 patients with histologically verified NAFLD (56 with NASH, 14 with non-NASH) and 12 controls. RESULTS: PTX3 and TNF-α levels were found significantly higher in the NAFLD group than in the control group (4.1 ± 2.3 vs. 1.3 ± 0.8 ng/mL, P < 0.001, and 7.6 ± 4.1 vs. 3.3 ± 1.3 pg/mL, P < 0.001 respectively) and in biopsy proven NASH subgroup than non-NASH subgroup (4.6 ± 2.2 vs. 2.2 ± 1.7 ng/mL, P = 0.001, and 8.3 ± 4.3 vs. 4.6 ± 1.6 pg/mL, P = 0.001 respectively). To discriminate NASH from non-NASH PTX3 had 91.1% sensitivity and 71.4% specificity at the cutoff value of 2.45 ng/mL. Plasma PTX3 levels showed correlation with NAFLD activity score, fibrosis stage and steatosis grade (r = 0.659, P < 0.001; r = 0.354, P < 0.01; and r = 0.455, P < 0.001, respectively). CONCLUSION: This study demonstrated markedly higher PTX3 levels in NAFLD patients compared with controls, and in biopsy proven NASH patients compared with non-NASH ones. Thus, in this cohort we showed that plasma PTX3 may be a promising biomarker for the presence of NASH.

The Relationship of Serum Hemojuvelin and Hepcidin Levels with Iron Overload in Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIMS: Mild iron overload is frequently reported in patients with nonalcoholic fatty liver disease (NAFLD). Hepcidin is the master iron-regulatory peptide and hemojuvelin (HJV) is the key regulator of iron-dependent secretion of hepcidin. The aims of this study were to evaluate serum HJV and hepcidin levels in patients with biopsy-proven NAFLD with and without hepatic iron overload, and to identify potential associations of HJV and hepcidin with the clinical characteristics of the patients enrolled. METHODS: Serum levels of HJV and hepcidin were measured in 66 NAFLD patients with (n=12) and without (n=54) iron overload, and controls (n=35) by enzyme-linked immunosorbent assay. Hemojuvelin and hepcidin levels were assessed in relation to clinical characteristics and liver histologic evaluation of the participants. RESULTS: Significantly lower serum HJV (281.1 [239.2-353.6] vs. 584.8 [440.3-661] ng/ml, p<0.001) and similar serum hepcidin levels (60.5+/-31.1 vs. 55.8+/-11.9 ng/ml, p=0.285) were found in NAFLD patients when compared to controls. Iron-overloaded NAFLD patients had significantly lower HJV (249.9 [187.6-296.3] vs. 292.9 [243-435] ng/ml, p=0.032) and significantly higher hepcidin (78.4+/-35.5 vs. 56.5+/-28.9ng/ml, p=0.027) levels than NAFLD patients without iron overload. Fibrosis stage was significantly higher in iron overloaded NAFLD group (p<0.001). Ferritin levels correlated significantly both with HOMA-IR (r=0.368, p=0.002) and fibrosis stage (r=0.571, p<0.001). CONCLUSIONS: Our findings suggest that HJV levels are low in NAFLD and even lower in iron overloaded NAFLD, while hepcidin levels are higher in NAFLD with iron overload. The gradually decreased HJV and increased hepcidin concentrations in our patients most likely reflect the physiological response to iron accumulation in the liver.