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Urinary Biomarkers (urinary + biomarker)
Selected AbstractsUrinary biomarker profiling in transitional cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 11 2006Nicholas P. Munro Abstract Urinary biomarkers or profiles that allow noninvasive detection of recurrent transitional cell carcinoma (TCC) of the bladder are urgently needed. We obtained duplicate proteomic (SELDI) profiles from 227 subjects (118 TCC, 77 healthy controls and 32 controls with benign urological conditions) and used linear mixed effects models to identify peaks that are differentially expressed between TCC and controls and within TCC subgroups. A Random Forest classifier was trained on 130 profiles to develop an algorithm to predict the presence of TCC in a randomly selected initial test set (n = 54) and an independent validation set (n = 43) several months later. Twenty two peaks were differentially expressed between all TCC and controls (p < 10,7). However potential confounding effects of age, sex and analytical run were identified. In an age-matched sub-set, 23 peaks were differentially expressed between TCC and combined benign and healthy controls at the 0.005 significance level. Using the Random Forest classifier, TCC was predicted with 71.7% sensitivity and 62.5% specificity in the initial set and with 78.3% sensitivity and 65.0% specificity in the validation set after 6 months, compared with controls. Several peaks of importance were also identified in the linear mixed effects model. We conclude that SELDI profiling of urine samples can identify patients with TCC with comparable sensitivities and specificities to current tumor marker tests. This is the first time that reproducibility has been demonstrated on an independent test set analyzed several months later. Identification of the relevant peaks may facilitate multiplex marker assay development for detection of recurrent disease. © 2006 Wiley-Liss, Inc. [source] Use of thymosin ,15 as a urinary biomarker in human prostate cancerTHE PROSTATE, Issue 2 2005Lloyd M. Hutchinson Abstract BACKGROUND Additional prostate cancer (CaP) biomarkers are needed to increase the accuracy of diagnosis and to identify patients at risk of recurrence. In tissue-based assays, thymosin ,15 (T,15) has been linked to an aggressive CaP phenotype and correlated with future tumor recurrence. We hypothesized that T,15 may have clinical utility in biological fluids. METHODS T,15 was measured in urine from CaP patients; untreated (N,=,61), prostatectomy (RP, N,=,46), androgen deprivation therapy (ADT, N,=,14) and control groups; normal (N,=,52), genitourinary carcinoma (N,=,15), non-malignant prostate disease (N,=,81), and other urology (N,=,73). We evaluated the utility of urinary T,15 for CaP diagnosis, alone or in combination with prostate-specific antigen (PSA), and the relationship to CaP progression. RESULTS A normal threshold of 40 (ng/dl)/(,g_protein/mg_creatinine) was defined using receiver operating characteristic analysis and marked the 19th centile for age-matched controls. The proportion of untreated CaP patients with urinary T,15 above the threshold was significantly higher than normal and genitourinary disease controls (P,<,0.001). RP caused urinary T,15 to drop significantly (P,=,0.005). Pre-surgery T,15 concentrations greater than the normal threshold may confer greater risk of CaP recurrence. Relative to normal controls, patients receiving ADT for aggressive CaP were 12 times more likely to have elevated urinary T,15 (P,=,0.001, 95% CI,=,2.8, 51.8). Combining PSA and T,15 (PSA,>,4, or PSA,>,2.5, T,15,>,40, or PSA,=,2.5, T,15,>,90) provided the same sensitivity as a 2.5 ng/ml PSA cutoff, but markedly improved diagnostic specificity. CONCLUSIONS We report that T,15 is a urinary biomarker for CaP and suggest that T,15, in combination with PSA, can be used to improve both the sensitivity and specificity of CaP diagnosis. © 2005 Wiley-Liss, Inc. [source] Identification of rat urinary glycoproteome captured by three lectins using gel and LC-based proteomicsELECTROPHORESIS, Issue 21 2008Pyong-Gon Moon Abstract Many different types of urine proteome studies have been done, but urine glycoprotein studies are insufficient. Therefore, we studied the glycoproteins from rat urine, which could be used to identify biomarkers in an animal model. First, urinary proteins were prepared by using the dialysis and lyophilizing methods from rat urine. Glycoproteins enriched with lectin affinity purification, concanavalin A, jacalin and wheat germ agglutinin from the urinary proteins were separated by means of reverse-phase fast protein LC (FPLC) or 1-D PAGE. Each FPLC fraction and 1-D PAGE gel band were trypsin-digested and analyzed by means of nanoLC-MS/MS. LC-MS/MS analyses were carried out by using linear ion trap MS. A total of 318 rat urinary glycoproteins were identified from the FPLC fractions and gel bands; approximately 90% of identified proteins were confirmed as glycoproteins in Swiss-Prot. Many glycoproteins, known as biomarkers, including C-reactive protein, uromodulin, amyloid beta A4 protein, alpha-1-inhibitor 3, vitamin D-binding protein, kallikrein 3 and fetuin-A were identified in this study. By studying urinary glycoproteins collected from rat, these results may help to assist in identifying urinary biomarkers regarding various types of disease models. [source] Urinary L-FABP and anaemia: distinct roles of urinary markers in type 2 diabetesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2010M. Von Eynatten Eur J Clin Invest 2010; 40 (2): 95,102 Abstract Background, Urinary liver-type fatty acid binding protein (L-FABP) and kidney injury molecule (KIM)-1, novel urinary biomarkers of renal tubulointerstitial function, have previously been associated with acute ischaemic kidney injury. We studied the clinical significance of urinary L-FABP, KIM-1 and N -acetyl-,-glucosaminidase (NAG) as potential markers of renal function and chronic ischaemic injury in patients with diabetic nephropathy. Material and methods, A total of 130 type 2 diabetes patients with early diabetic nephropathy and 40 healthy controls were studied. Urinary L-FABP, KIM-1, NAG, albumin excretion rate (AER) and creatinine clearance were obtained from 24-h urine samples, and correlated with measures of red blood cell count, renal function and metabolic control. Results, Urinary L-FABP was significantly increased in diabetes patients compared with healthy controls [8·1 (interquartile 0·6,11·6) vs. 2·4 (0·5,3·6) ,g/g creatinine, P < 0·001] and correlated with AER (r = 0·276, P = 0·002), creatinine clearance (r = ,0·189, P = 0·033) and haemoglobin levels (r = ,0·190, P = 0·030). In multivariable linear regression analysis, haemoglobin (, = ,0·247, P = 0·015) and AER (, = 0·198, P = 0·046) were significant predictors of urinary L-FABP. Prevalent anaemia was independently associated with a 6-fold risk for increased tubulointerstitial kidney damage (upper vs. lower two L-FABP tertiles: OR, 6·06; 95% CI: 1·65,22·23; P = 0·007). Urinary KIM-1 was not significantly associated with kidney function, AER, or measures of red blood cell count while urinary NAG was associated with parameters of glucose control and renal function. Conclusions, Different urinary biomarkers may reflect distinct pathophysiological mechanisms of tubulointerstitial damage in early diabetic nephropathy: Urinary L-FABP could be a novel biomarker for chronic intrarenal ischaemia. [source] Exposure to the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokers from 3 populations with different risks of lung cancerINTERNATIONAL JOURNAL OF CANCER, Issue 10 2009Kiersten S. Derby Abstract Native Hawaiian smokers are at higher risk and Japanese-American smokers at lower risk of lung cancer (LC), compared with white smokers, even after accounting for smoking history. Because variation in carcinogen exposure/metabolism may occur separately of smoking amount, we compared urinary biomarkers of uptake and detoxification of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK),a potent lung carcinogen,among 578 smokers in these ethnic/racial groups in Hawaii. We measured the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc) and examined total NNAL (NNAL + NNAL-Gluc) and the NNAL detoxification ratio (NNAL-Gluc:NNAL). Native Hawaiians and Japanese,Americans had lower age- and sex-adjusted mean total NNAL, compared with whites. When further adjusting for urinary nicotine equivalents (the sum of nicotine, cotinine, trans -3,-hydroxycotinine and their respective glucuronides), only the difference between Japanese,Americans and whites was eliminated. Therefore, consistent with their lower LC risk, a lower cigarette smoke exposure explains the lower NNK dose of Japanese,Americans, but it does not explain that of Native Hawaiians. The mean detoxification ratio was also lower in Native Hawaiians and Japanese,Americans, compared with whites, even after adjusting for nicotine equivalents (p < 0.0001). Lower NNAL glucuronidation in Native Hawaiians might contribute to their increased LC risk; however, this is inconsistent with the low glucuronidation ratio similarly observed in the low-risk Japanese-American group and because Native Hawaiians had lower total NNAL levels. Thus, exposure and detoxification of NNK are unlikely to explain, by themselves, the differences in LC risk among the 3 populations studied. © 2009 UICC [source] Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS): A new proteomic urinary test for patients with urolithiasisJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2004Peter A. Cadieux Abstract SELDI-TOF-MS is a highly sensitive protein-analysis tool capable of detecting minute protein profile differences between biological samples. As proteins have been associated with urinary tract calculi, protein-based urinalysis may offer insights into their diagnosis. The purpose of this study was to evaluate SELDI-TOF-MS as a potential method for identifying urinary biomarkers of urolithiasis. Midstream sterile urine samples were obtained from 25 male patients with a confirmed diagnosis of urolithiasis (test group) and 25 male subjects with no known history of the disease (controls). Urinary levels of oxalate, total protein, albumin, and osteopontin were determined. Protein profiles were generated using SELDI-TOF-MS. SELDI-TOF-MS profiling revealed a relationship between protein peak intensities at 67 and 24 kDa that differed between the two groups. The ratio of p67:p24 was found to be less than 1.0 in all of the control samples (mean 0.26), while 18 out of 25 (72%) of the test group samples displayed a ratio greater than 1.0 (total group mean 4.75, P<0.001). Albumin, total protein, and oxalate levels were higher in the test group than the controls. Although SELDI-TOF-MS is not yet in widespread use in hospital and diagnostic laboratories, this system represents a promising new method for rapidly identifying patients with urolithiasis. J. Clin. Lab. Anal. 18:170,175, 2004. © 2004 Wiley-Liss, Inc. [source] Analysis of urinary biomarkers for exposure to alkyl benzenes by isotope dilution gas chromatography-mass spectrometryJOURNAL OF SEPARATION SCIENCE, JSS, Issue 18 2005Adriaan A. S. Marais Abstract A validated GC-MS method for the analysis of urinary metabolites of alkyl benzenes is reported. Metabolites for exposure to toluene, xylene and ethylbenzene were analyzed simultaneously using stable isotope substituted internal standards. The method entailed acidic deconjugation of urine samples followed by extractive alkylation with pentafluorobenzyl bromide as alkylating agent. The resulting pentafluorobenzyl derivatives of ortho -, meta -, para -cresol, mandelic acid (MA), hippuric acid (HA) and ortho -, meta -, para -methylhippuric acid (MHA) were then quantified by SIM. Optimized reaction conditions for the extractive alkylation step are reported. The derivatives were found to be sufficiently stable for overnight batch analysis. The LODs were below 0.1 ,mol/L for the cresols and below 1 ,mol/L for MA and the HAs. Within-batch precision for o -MHA was 7%, for m -MHA 5%, for p -MHA 5.2% and below 5% for the rest of the analytes. [source] Review: Neutrophil gelatinase-associated lipocalin: A troponin-like biomarker for human acute kidney injuryNEPHROLOGY, Issue 4 2010PRASAD DEVARAJAN ABSTRACT Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which currently depends on functional markers such as serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers of structural kidney injury (akin to troponin in acute myocardial injury) has hampered our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The discovery, translation and validation of neutrophil gelatinase-associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed. NGAL is emerging as an excellent stand-alone troponin-like structural biomarker in the plasma and urine for the early diagnosis of AKI, and for the prediction of clinical outcomes such as dialysis requirement and mortality in several common clinical scenarios. The approach of using NGAL as a trigger to initiate and monitor therapies for AKI, and as a safety biomarker when using potentially nephrotoxic agents, is also promising. In addition, it is hoped that the use of sensitive and specific biomarkers such as NGAL as endpoints in clinical trials will result in a reduction in required sample sizes, and hence the cost incurred. Furthermore, predictive biomarkers like NGAL may play a critical role in expediting the drug development process. However, given the complexity of AKI, additional biomarkers (perhaps a panel of plasma and urinary biomarkers) may eventually need to be developed and validated for optimal progress to occur. [source] Detection of urinary biomarkers for early diagnosis of acute renal allograft rejection by proteomic analysisPROTEOMICS - CLINICAL APPLICATIONS, Issue 6 2009Xiongfei Jia Abstract Acute allograft rejection has been recognized as a major impediment to improved success in renal transplantation. Timely detection and control of rejection are very important for the improvement in long-term renal allograft survival. Thus, biomarkers for early diagnosis of acute rejection are required urgently to clinical medication. This study seeks to search for such biomarker candidates by comparing patients' pre-treatment urinary protein profiling with their post-treatment urinary protein profiling. A total of 15 significantly and consistently down-regulated protein candidates were identified. Among them, alpha-1-antichymotrypsin precursor (AACT), tumor rejection antigen gp96 (GP96) and Zn-Alpha-2-Glycoprotein (ZAG) were selected for further analysis. The results indicated that Western Blot assay of AACT, GP96 and ZAG had advanced the diagnosis time of acute renal rejection by 3 days, compared with current standard clinical observation and laboratory examination. Furthermore, the double-blind detection revealed that the accuracy, sensitivity and specificity of the diagnosis of acute renal rejection of AACT, GP96 and ZAG were 66.67%/100%/60%, 83.33%/100%/80% and 66.67%/100%/60%, respectively, and 100%/100%/100% in combination. In conclusion, urinary protein AACT, GP96 and ZAG could be a set of potential biomarkers for early non-invasive diagnosis of the acute rejection after renal transplantation. [source] Dynamic urinary proteomic analysis reveals stable proteins to be potential biomarkersPROTEOMICS - CLINICAL APPLICATIONS, Issue 3 2009Wei Sun Abstract Human urinary proteome analysis is a convenient and efficient approach for understanding disease processes affecting the kidney and urogenital tract. Many potential biomarkers have been identified in previous differential analyses; however, dynamic variations of the urinary proteome have not been intensively studied, and it is difficult to conclude that potential biomarkers are genuinely associated with disease rather then simply being physiological proteome variations. In this paper, pooled and individual urine samples were used to analyze dynamic variations in the urinary proteome. Five types of pooled samples (first morning void, second morning void, excessive water-drinking void, random void, and 24,h void) collected in 1,day from six volunteers were used to analyze intra-day variations. Six pairs of first morning voids collected a week apart were used to study inter-day, inter-individual, and inter-gender variations. The intra-day, inter-day, inter-individual, and inter-gender variation analyses showed that many proteins were constantly present with relatively stable abundances, and some of these had earlier been reported as potential disease biomarkers. In terms of sensitivity, the main components of the five intra-day urinary proteomes were similar, and the second morning void is recommended for clinical proteome analysis. The advantages and disadvantages of pooling samples are also discussed. The data presented describe a pool of stable urinary proteins seen under different physiological conditions. Any significant qualitative or quantitative changes in these stable proteins may mean that such proteins could serve as potential urinary biomarkers. [source] Development and validation of a gas chromatography/mass spectrometry metabonomic platform for the global profiling of urinary metabolitesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2008Kishore K. Pasikanti This paper presents a simple and reliable gas chromatography/mass spectrometry (GC/MS) method for the metabonomic analysis of human urine samples. The sample preparation involved the depletion of excess urea via treatment with urease and subsequent protein precipitation using ice-cold ethanol. An aliquot of the mixture was separated, dried, trimethylsilyl (TMS)-derivatized and 1.0,µL of the derivatized extract was injected into the GC/MS system via split injection (1:10). Approximately 150 putative metabolites belonging to different chemical classes were identified from the pooled human urine samples. All the identified metabolites were selected to evaluate precision and stability of the GC/MS assay. More than 95% of the metabolites demonstrated good reproducibility, with intra-day and inter-day precision values below 15%. Metabolic profiling of 53 healthy male and female urine samples in combination with pattern recognition techniques was performed to further validate the GC/MS metabolite profiling assay. Principal component analysis (PCA) followed by orthogonal partial least squares analysis (OPLS) revealed differences between urinary metabolite profiles of healthy male and female subjects. This validated GC/MS metabolic profiling method may be further applied to the metabonomic screening of urinary biomarkers in clinical studies. Copyright © 2008 John Wiley & Sons, Ltd. [source] The combination of the biomarkers urinary C-terminal telopeptide of type II collagen, serum cartilage oligomeric matrix protein, and serum chondroitin sulfate 846 reflects cartilage damage in hemophilic arthropathyARTHRITIS & RHEUMATISM, Issue 1 2009Nathalie W. D. Jansen Objective Hemophilic arthropathy, with characteristics of inflammatory (rheumatoid arthritis) and degenerative (osteoarthritis) joint damage, occurs at an early age, is associated with minor comorbidity, and is restricted to 3 pairs of large joints. The aim of this study was to determine whether commonly used serum and/or urinary biomarkers of cartilage and bone turnover for which assay kits are commercially available are associated with the severity of joint damage in patients with various degrees of hemophilic arthropathy and, thus, whether this disease could be useful in the identification and evaluation of such biomarkers. Methods Blood and urine samples were collected from 36 patients with various degrees of hemophilic arthropathy. Commercially available assays for the most frequently investigated serum and urine biomarkers were performed: urinary C-terminal telopeptide of type I collagen (CTX-I), urinary CTX-II, serum CTX-I, serum CTX-II, serum cartilage oligomeric matrix protein (COMP), serum cartilage cleavage products C1,2C and C2C, and serum chondroitin sulfate 846 (CS-846). Radiographs of the ankles, knees, and elbows in all patients were evaluated for the degree of joint damage according to the Pettersson score, which is based on cartilage and periarticular bone changes and is specific for hemophilic arthropathy. Results Urinary CTX-II, serum C1,2C, and serum CS-846 levels correlated with the overall Pettersson score and with the joint space narrowing component. Regression analysis showed that combined indexes of different markers increased the degree of correlation for the combination of urinary CTX-II, serum COMP, and serum CS-846. Bone-specific markers (urinary/serum CTX-I and serum C1,2C) did not correlate with specific bone-related items of the Pettersson score (osteoporosis and erosions). Conclusion These results support the idea that a combination of biomarkers relates significantly better to the severity of joint damage than do individual biomarkers. The combination of urinary CTX-II, serum COMP, and serum CS-846 correlated best with the degree of arthropathy. Because of its specific characteristics and restricted involvement, hemophilic arthropathy may prove useful in the screening of newly developed biomarkers of joint damage. [source] | ||||||||||||||||