PURPOSE: To determine whether levels of nerve growth factor (NGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to objectively assess overactive bladder syndrome (OAB) treatment outcome and to evaluate the effects of fixed-dose fesoterodine on OAB symptoms. MATERIALS AND METHODS: This study included 124 participants (62 patients with OAB and 62 controls) in Severance Hospital between 2010 and 2012. In patients with OAB, 4 mg fesoterodine was administered once daily. Repeated evaluations of putative biomarker levels, urine creatinine (Cr) levels, and questionnaire responses, including the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire (OAB q), were performed from baseline to 16 weeks. RESULTS: Urinary levels of NGF/Cr (OAB: 1.13+/-0.9 pg/mg; control: 0.5+/-0.29 pg/mg) and HB-EGF/Cr (OAB: 8.73+/-6.55 pg/mg; control: 4.45+/-2.93 pg/mg) were significantly higher in subjects with OAB than in controls (p<0.001). After 16 weeks of fixed-dose fesoterodine treatment, urinary NGF/Cr levels (baseline: 1.13+/-0.08 pg/mg; 16 weeks: 0.60+/-0.4 pg/mg; p=0.02) and HB-EGF/Cr levels significantly decreased (baseline: 8.73+/-6.55 pg/mg; 16 weeks: 4.72+/-2.69 pg/mg; p=0.03, respectively). Both the OABSS and OAB q scores improved (p<0.001). However, there were no a statistically significant correlations between these urinary markers and symptomatic scores. CONCLUSION: Urinary levels of NGF and HB-EGF may be potential biomarkers for evaluating outcome of OAB treatment. Fixed-dose fesoterodine improved OAB symptoms. Future studies are needed to further examine the significance of urinary NGF and HB-EGF levels as therapeutic markers for OAB.
Adult ; Benzhydryl Compounds/pharmacology/*therapeutic use ; Biological Markers/urine ; Case-Control Studies ; Creatinine/urine ; Female ; Heparin-binding EGF-like Growth Factor/*urine ; Humans ; Male ; Middle Aged ; Nerve Growth Factor/*urine ; Questionnaires ; Treatment Outcome ; Urinary Bladder, Overactive/*drug therapy/physiopathology/*urine ; Urodynamics

PURPOSE: Antenatal hydronephrosis (AH) is found in 0.5%-1% of neonates. The aim of the study was to assess the urinary concentrations of 3 biomarkers, endothelin-1 (ET-1), monocyte chemotactic peptide-1 (MCP-1), and N-acetyl-glucosaminidase (NAG) in severely hydronephrotic neonates. MATERIALS AND METHODS: Neonates with a history of prenatal hydronephrosis were enrolled in the prospective study in 2 groups. Group 1 included neonates with severe forms of obstruction requiring surgical intervention and group 2 included neonates with milder forms of obstruction without any functional impairment. Fresh voided urinary levels of ET-1, MCP-1, and NAG were measured and their ratios to urinary Cr were calculated. RESULTS: Fourty-two neonates were enrolled into the 2 groups: group 1, 24 patients (21 male, 3 female); group 2, 18 neonates (16 male, 2 female). There were no statistically significant differences between urinary ET-1, NAG, MCP-1 values, and ET-1/Cr and NAG/Cr ratios in groups 1 and 2. The urinary MCP-1/Cr ratio was significantly higher in group 1 than in group 2. For comparison of groups 1 and 2, the cut-off values were measured as 0.5709 ng/mg (sensitivity, 75%; specificity, 67%; positive predictive value [PPV], 71%; negative predictive value [NPV], 71%), 0.927 ng/mg (sensitivity, 77%; specificity, 72%; PPV, 77%; NPV, 72%), and 1.1913 IU/mg (sensitivity, 62%; specificity, 67%; PPV, 68%; NPV, 60%) for ET-1/Cr, MCP-1/Cr, and NAG/Cr ratios, respectively. CONCLUSIONS: The urinary MCP-1/Cr ratio is significantly elevated in neonates with severe obstruction requiring surgical intervention. Based upon these results, urinary MCP-1/Cr may be useful in identification of severe obstructive hydronephrosis in neonates.
Acetylglucosaminidase/*urine ; Biological Markers/urine ; Chemokine CCL2/*urine ; Endothelin-1/*urine ; Female ; Humans ; Hydronephrosis/*congenital/etiology/surgery/ultrasonography ; Infant, Newborn ; Male ; Predictive Value of Tests ; Prospective Studies ; Sensitivity and Specificity ; Ureteral Obstruction/complications/*diagnosis/surgery

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker in the detection of kidney injury. Early diagnosis of urinary tract infection (UTI), one of the most common infections in children, is important in order to avert long-term consequences. We assessed whether serum NGAL (sNGAL) or urine NGAL (uNGAL) would be reliable markers of UTI and evaluated the appropriate diagnostic cutoff value for the screening of UTI in children. METHODS: A total of 812 urine specimens and 323 serum samples, collected from pediatric patients, were analyzed. UTI was diagnosed on the basis of culture results and symptoms reported by the patients. NGAL values were measured by using ELISA. RESULTS: NGAL values were more elevated in the UTI cases than in the non-UTI cases, but the difference between the values were not statistically significant (P=0.190 for sNGAL and P=0.064 for uNGAL). The optimal diagnostic cutoff values of sNGAL and uNGAL for UTI screening were 65.25 ng/mL and 5.75 ng/mL, respectively. CONCLUSIONS: We suggest that it is not appropriate to use NGAL as a marker for early diagnosis of UTI in children.
Acute-Phase Proteins/*urine ; Area Under Curve ; Biological Markers/blood/urine ; Child ; Child, Preschool ; Early Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Lipocalins/*blood/*urine ; Male ; Mass Screening/*methods ; Proto-Oncogene Proteins/*blood/*urine ; ROC Curve ; Urinary Tract Infections/*blood/*urine

BACKGROUND/AIMS: beta2-microglobulin (beta2-MG) is freely filtered at the glomerulus and subsequently reabsorbed and catabolized by proximal renal tubular cells. Urinary beta2-MG is an early and sensitive biomarker of acute kidney injury; however, its utility as a biomarker of immunoglobulin A nephropathy (IgAN) is unclear. METHODS: We included urinary beta2-MG levels in the routine laboratory examination of all inpatients with biopsy-proven IgAN at our hospital from 2006 to 2010. We retrospectively analyzed the correlation between beta2-MG levels and clinical parameters as a prognostic biomarker of IgAN. RESULTS: A total of 51 patients (30 males, 21 females; mean age, 33.01 +/- 12.73 years) with IgAN were included in this study. Initial demographic, clinical, and laboratory data for all patients are listed. The mean initial estimated glomerular filtration rate and 24-hour urine protein levels were 94.69 +/- 34.78 mL/min/1.73 m2 and 1.28 +/- 1.75 g/day, respectively. The mean level of urinary beta2-MG was 1.92 +/- 7.38 microg/mg creatinine. There was a significant correlation between initial serum creatinine (iSCr), urine protein creatinine ratio (UPCR), and the level of beta2-MG (r = 0.744, r = 0.667, p < 0.01). There was also a significant correlation between renal function tests and the level of urinary beta2-MG (p < 0.01). Cox regression analysis showed that albumin, beta2-MG, iSCr, and UPCR were significant predictors of disease progression in IgAN. CONCLUSIONS: Urinary beta2-MG levels showed a significant correlation with renal function and proteinuria in IgAN. Thus, we propose that urinary beta2-MG may be an additional prognostic factor in patients with IgAN.
Adult ; Biological Markers/blood/urine ; Biopsy ; Creatinine/blood/urine ; Disease Progression ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/blood/diagnosis/physiopathology/*urine ; Humans ; Inpatients ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Proteinuria/blood/diagnosis/physiopathology/*urine ; Risk Factors ; Young Adult ; beta 2-Microglobulin/*urine

Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery.
Acute Kidney Injury/blood/*chemically induced/*urine ; Biological Markers/urine ; Cardiac Catheterization/*adverse effects ; Child ; Contrast Media/adverse effects/diagnostic use ; Fatty Acid-Binding Proteins/*urine ; Female ; Heart Defects, Congenital/complications/*radiography ; Humans ; Iohexol/adverse effects/*analogs & derivatives/diagnostic use ; Male ; Radiography, Interventional/adverse effects ; Reproducibility of Results ; Sensitivity and Specificity

Although several urinary biomarkers have been validated as early diagnostic markers of acute kidney injury (AKI), their usefulness as outcome predictors is not well established. This study aimed to determine the diagnostic and prognostic abilities of urinary liver-type fatty acid-binding protein (L-FABP) in heterogeneous critically ill patients. We prospectively collected data on patients admitted to medical and surgical intensive care units (ICUs) from July 2010 to June 2011. Urine neutrophil gelatinase-associated lipocalin (NGAL) and L-FABP at the time of ICU admission were quantitated. Of the 145 patients, 54 (37.2%) had AKI defined by the Acute Kidney Injury Network (AKIN) criteria. AKI patients showed significantly higher level of urinary NGAL and L-FABP and also higher mortality than non-AKI patients. The diagnostic performances, assessed by the area under the ROC curve, were 0.773 for NGAL and 0.780 for L-FABP, demonstrating their usefulness in diagnosing AKI. In multivariate Cox analysis, urinary L-FABP was an independent predictor for 90-day mortality. Urinary L-FABP seems to be promising both for the diagnosis of AKI and for the prediction of prognosis in heterogeneous ICU patients. It needs to be further validated for clinical utility.
Acute Kidney Injury/*diagnosis/mortality/surgery ; Acute-Phase Proteins/urine ; Adult ; Aged ; Area Under Curve ; Biological Markers/urine ; Critical Illness ; Fatty Acid-Binding Proteins/*urine ; Female ; Humans ; Intensive Care Units ; Kaplan-Meier Estimate ; Lipocalins/urine ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Proto-Oncogene Proteins/urine ; ROC Curve

Urinary biomarkers of acute kidney injury (AKI) have been revealed recently to be useful for prior prediction of AKI. However, it is unclear whether these urinary biomarkers can also detect recovery from established AKI. Urinary biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, were measured every 2 days for 8 days in 66 patients with AKI. At day 0, there were no significant differences in plasma creatinine, BUN, and urine cystatin C between AKI patients in the recovery (n = 33) and non-recovery (n = 33) groups. Plasma creatinine concentrations were significantly lower in the recovery group (3.0 +/- 2.0 mg/dL) than in the non-recovery group (5.4 +/- 1.9 mg/dL) on day 4 after AKI diagnosis (P < 0.001). In contrast, there were significant differences in urine NGAL between the two groups starting on day 0 (297.2 +/- 201.4 vs 407.6 +/- 190.4 ng/mL, P = 0.025) through the end of the study (123.7 +/- 119.0 vs 434.3 +/- 121.5 ng/mL, P < 0.001). The multiple logistic regression analysis showed that urine NGAL could independently predict recovery from AKI. Conclusively, this prospective observational study demonstrates that urine NGAL can be a highly versatile marker for early detection of the recovery phase in established AKI patients.
Acute Kidney Injury/*diagnosis/pathology ; Acute-Phase Proteins/urine ; Adolescent ; Adult ; Aged ; Biological Markers/*urine ; Creatinine/blood ; Cystatin C/urine ; Female ; Humans ; Lipocalins/urine ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Proto-Oncogene Proteins/urine ; ROC Curve ; Recovery of Function ; Young Adult

Previous studies reported the beneficial effect of erythropoietin (EPO) in acute injuries. We followed patients with and without acute kidney injury (AKI) after coronary artery bypass grafting (CABG) and evaluated the effect of EPO on long-term outcome. We also assessed the efficacy of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a predictive marker of AKI. Seventy-one patients scheduled for elective CABG were randomly given either 300 U/kg of EPO or saline before CABG. The primary outcome was AKI, and the secondary outcome was the all-cause-mortality and composite of all-cause-mortality and end stage renal disease (ESRD). Twenty-one patients had AKI, 14 (66.7%) in the placebo group and 7 (33.3%) in the EPO group (P = 0.05). Also, uNGAL was higher in the patients with AKI than in those without AKI at baseline, 2, 4, 24, and 72 hr after CABG (P = 0.011). Among patients with AKI, 2-week creatinine (Cr) was not different from baseline Cr in the EPO group, but 2-week Cr was significantly higher than baseline Cr in the placebo group (P = 0.009). All-cause-mortality (P = 0.022) and the composite of all-cause-mortality and ESRD (P = 0.003) were reduced by EPO. EPO reduces all-cause-mortality and ESRD in patients with AKI, largely due to the beneficial effect of EPO on recovery after AKI.
Acute Kidney Injury/etiology/mortality/*prevention & control ; Acute-Phase Proteins/urine ; Aged ; Aged, 80 and over ; Biological Markers/urine ; Coronary Artery Bypass/*adverse effects ; Creatinine/analysis ; Double-Blind Method ; Erythropoietin/*therapeutic use ; Female ; Hematinics/*therapeutic use ; Humans ; Kaplan-Meier Estimate ; Lipocalins/urine ; Male ; Middle Aged ; Placebo Effect ; Prospective Studies ; Proto-Oncogene Proteins/urine ; ROC Curve ; Recombinant Proteins/therapeutic use ; Risk Factors ; Treatment Outcome

Mercury is a toxic and non-essential metal in the human body. Mercury is ubiquitously distributed in the environment, present in natural products, and exists extensively in items encountered in daily life. There are three forms of mercury, i.e., elemental (or metallic) mercury, inorganic mercury compounds, and organic mercury compounds. This review examines the toxicity of elemental mercury and inorganic mercury compounds. Inorganic mercury compounds are water soluble with a bioavailability of 7% to 15% after ingestion; they are also irritants and cause gastrointestinal symptoms. Upon entering the body, inorganic mercury compounds are accumulated mainly in the kidneys and produce kidney damage. In contrast, human exposure to elemental mercury is mainly by inhalation, followed by rapid absorption and distribution in all major organs. Elemental mercury from ingestion is poorly absorbed with a bioavailability of less than 0.01%. The primary target organs of elemental mercury are the brain and kidney. Elemental mercury is lipid soluble and can cross the blood-brain barrier, while inorganic mercury compounds are not lipid soluble, rendering them unable to cross the blood-brain barrier. Elemental mercury may also enter the brain from the nasal cavity through the olfactory pathway. The blood mercury is a useful biomarker after short-term and high-level exposure, whereas the urine mercury is the ideal biomarker for long-term exposure to both elemental and inorganic mercury, and also as a good indicator of body burden. This review discusses the common sources of mercury exposure, skin lightening products containing mercury and mercury release from dental amalgam filling, two issues that happen in daily life, bear significant public health importance, and yet undergo extensive debate on their safety.
Biological Availability ; Biological Markers/blood/urine ; Blood-Brain Barrier/metabolism ; Body Burden ; Dental Amalgam/chemistry/metabolism ; *Environmental Exposure ; Humans ; Mercury/chemistry/*metabolism ; Mercury Compounds/chemistry/*metabolism ; Skin Lightening Preparations/chemistry/metabolism

Changes in renal function are one of the most common manifestations of severe illness. There is a clinical need to intervene early with proven treatments in patients with potentially deleterious changes in renal function. Unfortunately progress has been hindered by poor definitions of renal dysfunction and a lack of early biomarkers of renal injury. In recent years, the definitional problem has been addressed with the establishment of a new well-defined diagnostic entity, acute kidney injury (AKI), which encompasses the wide spectrum of kidney dysfunction, together with clearer definition and sub-classification of the cardio-renal syndromes. From the laboratory have emerged new biomarkers which allow early detection of AKI, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C. This review describes the new concepts of AKI and the cardio-renal syndromes as well as novel biomarkers which allow early detection of AKI. Panels of AKI biomarker tests are likely to revolutionise the diagnosis and management of critically ill patients in the coming years. Earlier diagnosis and intervention should significantly reduce the morbidity and mortality associated with acute kidney damage.
Acute Kidney Injury/*diagnosis ; Biological Markers/analysis/blood/urine ; Cystatin C/blood/urine ; Heart Failure/complications/etiology ; Humans ; Kidney Diseases/complications/*diagnosis/etiology ; Lipocalins/blood/urine ; Syndrome