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

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

Bone metastasis is common in lung cancer patient and the diagnosis of bone metastasis is usually made by using imaging techniques, especially bone scintigraphy. However, the diagnostic yield from bone scintigraphy is limited. The aim of this study is to assess the clinical usefulness of urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), urinary deoxypyridinoline (DPD), and serum alkaline phosphatase (ALP) in the assessment of bone metastasis in patients with lung cancer. Urinary NTx, DPD, and serum ALP were measured in 151 lung cancer patients (33 with and 118 without bone metastasis). Lung cancer patients with bone metastasis had a higher urinary excretion of NTx and DPD, and a higher serum ALP than those without bone metastasis. NTx had a better receiver operating characteristic (ROC) curve than DPD and ALP, since the areas under the ROC curve were 0.82, 0.79, and 0.71, respectively. Although correlation coefficients among NTx, DPD and ALP were significantly positive (p < 0.005), the strongest relationship was appeared between NTx and DPD (R=0.616). In conclusion, our results showed the utility of the new bone markers in detecting bone metastasis and suggested that measurement of urinary NTx was valid diagnostic method of bone metastasis from lung cancer.
Adult ; Aged ; Aged, 80 and over ; Alkaline Phosphatase/blood ; Amino Acids/urine ; Bone Neoplasms/blood/*secondary/urine ; Collagen/urine ; Humans ; Lung Neoplasms/*pathology ; Middle Aged ; Peptides/urine ; Predictive Value of Tests ; Research Support, Non-U.S. Gov't ; Tumor Markers, Biological/blood/*urine

To evaluate the implication of methymalonic acid (MMA) in the early diagnosis of neural tube defects (NTD), a quantitative assay for MMA was established by using gas chromatography-mass spectrometry with stable isotope of MMA as an internal standard. Amniotic fluid and maternal urine MMA concentration, maternal serum folate, red blood cell folate and vitamin B12 levels were measured in the middle term of NTD-affected and normal pregnancies. Amniotic fluid and maternal urine MMA concentrations in the middle term of NTD affected pregnancies (1.4 +/- 0.9 micromol/L, and 22.1 +/- 12.6 nmol/micromol creatinine) were significantly higher than that of normal pregnancies (1.0 +/- 0. 4 micromol/L, and 2.5 +/- 1.1 nmol/micromol creatinine). There was no significant difference between normal and NTD pregnancies for serum folate, red blood cell folate and vitamin B12 levels. The results suggested that MMAs in amniotic fluid and maternal urine are sensitive markers for early diagnosis of NTD. Vitamin B12 is an active cofactor involved in the remethylation of homocycteine and its deficiency is an independent risk factor for NTD. MMA is a specific and sensitive marker for intracellular vitamin B12 deficiency. This study suggests that it is necessary to monitor the vitamin B12 deficiency and advocates vitamin B12 supplementation with folate prevention program.
Amniotic Fluid/*chemistry ; Biological Markers/analysis ; Biological Markers/urine ; Folic Acid/blood ; Methylmalonic Acid/analysis ; Methylmalonic Acid/*urine ; Neural Tube Defects/*diagnosis ; Neural Tube Defects/metabolism ; Pregnancy Trimester, Second ; *Prenatal Diagnosis ; Vitamin B 12/blood

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

In diabetes mellitus, thickening of basement membrane in capillaries and small vessels is a well-known finding and important in the progression of diabetic microangiopathy. We evaluated whether the plasma levels of type IV collagen and fibronectin, which are important factors of basement membrane, are related with the presence of diabetic microangiopathy. Plasma type IV collagen and fibronectin levels were measured in 40 healthy controls (Mean +/- SD, age; 50.3 +/- 5.5 yr) and 94 diabetic patients (age; 52.4 +/- 13.5 yr) with and without microvascular complications. The mean plasma levels of type IV collagen (5.3 +/- 2.9 ng/ml) and fibronectin (474.4 +/- 119.4 ug/ml) in diabetic patients were significantly higher (p < 0.01) than in healthy controls (3.7 +/- 1.3 ng/ml and 319 +/- 50.9 ug/ml). The mean plasma level of type IV collagen in diabetic patients with complications (6.6 +/- 3.7 ng/ml) was significantly higher (p < 0.01) than in those without complications (4.3 +/- 1.7 ng/ml) and became higher in more complicated patients. Furthermore, the severity of retinopathy and several indicators of nephropathy such as serum BUN, creatinine and proteinuria were closely associated with plasma type IV collagen level and a significant correlation was found between plasma type IV collagen and creatinine clearance (r = -0.31, p < 0.001). There was no significant difference in plasma fibronectin concentrations, however, between the diabetic patients with complications and those without complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult ; Aged ; Biological Markers/blood ; Blood Proteins/urine ; Blood Urea Nitrogen ; Collagen/*blood ; Creatinine/blood ; Diabetic Angiopathies/*blood/diagnosis ; Diabetic Nephropathies/blood/diagnosis ; Diabetic Retinopathy/blood/diagnosis ; Female ; Fibronectins/*blood ; Human ; Male ; Middle Age

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

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: The clinical usefulness of urinary trypsinogen-2 dipstick test is still in controversy. We evaluated the usefulness of urinary trypsinogen-2 dipstick test in patients with acute pancreatitis. METHODS: Urinary trypsinogen-2 dipstick test was prospectively performed in 50 patients with acute pancreatitis, 50 patients with non-pancreatic abdominal pain, and 50 healthy controls. RESULTS: On admission, urinary trypsinogen-2 dipstick test was positive in 36 of 50 patients with acute pancreatitis (sensitivity, 72%) and in 4 of 50 patients with non-pancreatic abdominal pain (specificity, 92%). On the other hand, it was all negative in controls. The sensitivity and specificity of serum lipase were 78% and 94%, respectively. At 24 hours after admission, the positive rate of urinary trypsinogen-2 dipstick test rose from 72% to 94% (p=0.02). The results of urinary trypsinogen-2 dipstick test was positive in 14 of 15 patients with severe pancreatitis and 22 of 35 patients with mild pancreatitis according to the criteria by Atlanta International Symposium, 1992. CONCLUSIONS: Urinary trypsinogen-2 dipstick test is comparable to serum lipase in diagnosing acute pancreatitis. Delayed measurement and severe pancreatitis are more likely to yield positive results with urinary trypsinogen-2 dipstick test. Thus, we suggest that the cut-off value of urinary trypsinogen-2 dipstick test should be lowered to increase its sensitivity.
Acute Disease ; Adult ; Aged ; Biological Markers/analysis ; English Abstract ; Female ; Humans ; Lipase/blood ; Male ; Middle Aged ; Pancreatitis/*diagnosis ; Reagent Strips ; Sensitivity and Specificity ; Trypsinogen/*urine

To elucidate the changes in bone turnover during pregnancy and puerperium, we measured serially the levels of serum osteocalcin and urine deoxypyridinoline (Dpy) as markers of bone formation and bone resorption, respectively, in 22 healthy women with normal pregnancy. Nineteen non-pregnant women served as control. The Dpy levels increased significantly at 16 weeks of pregnancy and remained elevated thereafter. The levels of osteocalcin, however, were significantly decreased at 16 weeks of pregnancy and elevated later at 6 weeks postpartum. Bone turnover ratio (Dpy/osteocalcin) continued to rise during pregnancy, but returned to control levels 6 weeks after delivery. Dpy levels and bone turnover ratio during puerperium tended to be higher in 17 breast-feeding women than those of 5 exclusive bottle-feeders. In conclusion, bone resorption begins to increase from the second trimester of pregnancy and calcium release from bone tissue might play a major role in calcium homeostasis during the whole period of pregnancy as well as during lactation.
Adult ; Amino Acids/urine ; Analysis of Variance ; Biological Markers* ; Bone Resorption/physiopathology* ; Calcium/metabolism ; Female ; Human ; Lactation/physiology ; Osteocalcin/blood ; Osteoporosis/physiopathology* ; Pregnancy ; Pregnancy Complications/physiopathology* ; Puerperium/physiology*