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

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

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

This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Type 2 diabetic patients (n = 332) with normoalbuminuria (n = 210), microalbuminuria (n = 83) and macroalbuminuria (n = 42) were enrolled. Creatinine, urinary albumin levels, serum/urine cystatin C and estimated glomerular filtration rate (eGFR by MDRD [Modification of Diet in Renal Disease] and CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equations) were determined. The cystatin C levels of serum and urine increased with increasing degree of albuminuria, reaching higher levels in macroalbuminuric patients (P < 0.001). In multiple regression analysis, serum cystatin C was affected by C-reactive protein (CRP), sex, albumin-creatinine ratio (ACR) and eGFR. Urine cystatin C was affected by triglyceride, age, eGFR and ACR. In multivariate logistic analysis, cystatin C levels of serum and urine were identified as independent factors associated with eGFR < 60 mL/min/1.73 m2 estimated by MDRD equation in patients with normoalbuminuria. On the other hand, eGFR < 60 mL/min/1.73 m2 estimated by CKD-EPI equation was independently associated with low level of high-density lipoprotein in normoalbuminuric patients. The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria.
Aged ; Albuminuria/urine ; *Biological Markers/blood/urine ; Creatinine/blood/urine ; *Cystatin C/blood/urine ; Diabetes Mellitus, Type 2/*blood/physiopathology/*urine ; Diabetic Nephropathies/*blood/physiopathology/*urine ; Female ; Glomerular Filtration Rate ; Humans ; Kidney Function Tests ; Male ; Middle Aged ; ROC Curve ; Retrospective Studies

OBJECTIVES: This study assessed the factors that have an influence on the residents exposed to heavy metals, and we utilized the findings to establish the proper management of abandoned metal mines in the future. METHODS: For a total of 258 residents who lived close to abandoned mines in Gangwon-province and Gyeonggi-province, the exposure factors and biomarkers in their blood and urine were comparatively analyzed via multiple regression analysis. RESULTS: The blood levels of lead and mercury and the cadmium levels in urine were found to be higher in the study group than that in the average Korean. For the blood levels of heavy metals according to each exposure factor, all of them were found to be significantly higher in both of the group residing for a longer period of time and the group living closer to the source of pollutants. Multiple regression analysis disclosed that all the heavy metals, except lead, in their blood were significantly reduced in proportion to the increased distance of inhabitancy from the mines. Their other biomarkers were within the normal ranges. CONCLUSIONS: We found that the distance between the residential village and the mines was a factor that affects the blood level of heavy metals in the villagers. This finding could be an important factor when developing a management model for the areas that surround abandoned metal mines. (ED note: I much like this important study.)
Biological Markers/blood/urine ; Cadmium/blood/urine ; Cluster Analysis ; Environmental Exposure/*adverse effects ; Humans ; Lead/blood/urine ; Mercury/blood/urine ; Metals, Heavy/*blood/*urine ; Mining ; Republic of Korea ; Water Pollutants, Chemical/analysis ; Water Supply/analysis

Serum creatinine level is the most commonly used indices for assessment of glomerular filtration rate (GFR), even though these indices have been shown to have some limitations in clinical practice. We investigated the diagnostic efficacy of serum cystatin C compared to that of serum creatinine levels and identified the relating factors associated with changes in serum cystatin C levels in gout patients with renal impairment. A total of 68 gouty patients with renal impairment were enrolled in this study. Diagnostic efficacy of serum cystatin C levels was evaluated through non-parametric receiver operating characteristic (ROC) analysis. The risk factors for changes in serum cystatin C levels were confirmed using multivariate regression analysis. With 24-hr urine creatinine clearance (Ccr) as the reference for GFR, 1/cystatin C (r=0.702, P<0.001) showed a significantly higher correlation with Ccr than 1/creatinine (r=0.665, P<0.001). Multivariate correlation analysis demonstrated that the clinical parameters for increased serum cystatin C are a higher stage of chronic kidney disease, older age, use of allopurinol, and lower high density lipoprotein-cholesterol. The area under the curve (AUC) at ROC plots identified that of serum cystatin C was significantly greater than that of serum creatinine (AUC 0.804 of cystatin C and AUC 0.745 of creatinine). The study suggests that serum cystatin C is a reliable endogenous marker for the assessment of renal function or GFR in gout patients with renal impairment.
Age Factors ; Aged ; Allopurinol/therapeutic use ; Area Under Curve ; Biological Markers/metabolism ; Cholesterol, HDL/blood ; Creatinine/blood/urine ; Cystatin C/*blood ; Glomerular Filtration Rate ; Gout/complications/*diagnosis ; Gout Suppressants/therapeutic use ; Humans ; Male ; Middle Aged ; ROC Curve ; Renal Insufficiency/complications/*diagnosis ; Risk Factors

PURPOSE: To determine the levels of bone and cartilage turnover markers in men with ankylosing spondylitis (AS) and to investigate their associations with disease activity, bone mineral density, and radiographic damage of the spine. PATIENTS AND METHODS: This cross-sectional study enrolled 35 men with newly diagnosed AS. The bone mineral densities (BMD) of their lumbar spines and proximal femurs, Bath AS Disease Activity Index (BASDAI), and Bath AS Radiographic Index (BASRI) were evaluated. Urinary C-terminal telopeptide fragments of type I collagen (CTX-I) and type II collagen (CTX-II) levels were determined by enzyme-linked immunosorbent assay, and serum levels of bone-specific alkaline phosphatase (BALP) and osteocalcin were determined by an enzyme immunoassay. Levels of biochemical markers were compared with those of 70 age-matched healthy men. RESULTS: Patients with AS had significantly higher mean urinary CTX-I and CTX-II levels than control subjects (p < 0.05). Elevated urinary CTX-I levels correlated well with BASDAI, femoral BMD, and femoral T score (p < 0.05), and elevated urinary CTX-II levels correlated well with spinal BASRI (p < 0.05) in patients with AS. Mean serum BALP and osteocalcin levels did not differ between patients and controls and did not show any significant correlations with BMD, BASDAI, or BASRI in men with AS. Conclusions: Elevated CTX-I reflects disease activity and loss of femoral BMD while elevated CTX-II levels correlate well with radiographic damage of the spine, suggesting the usefulness of these markers for monitoring disease activity, loss of BMD, and radiographic damage in men with AS.
Adolescent ; Adult ; Alkaline Phosphatase/blood ; Biological Markers/*analysis/blood/urine ; *Bone Density ; Bone and Bones/*metabolism/radiation effects ; Cartilage/metabolism/radiation effects ; Collagen Type I/urine ; Collagen Type II/urine ; Cross-Sectional Studies ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoassay/methods ; Male ; Osteocalcin/blood ; Spondylitis, Ankylosing/*metabolism