Metabolic Changes In Urine Research Articles

Identifying Urinary Metabolic Changes With Vanadium And Polycyclic Aromatic Hydrocarbons Exposures Using Mass-Spectrometry-Based Metabolomics

Purpose: This study aims to investigate urinary metabolic changes after exposure to petrochemical complex pollutants, vanadium (V) and polycyclic aromatic hydrocarbons (PAHs). Methods: We recruited high exposure groups, who live near a petrochemical complex with higher urinary levels of V and 1-hydroxypyrene (1-OHP; PAHs biomarker), aged 9-15 (group A, n=39) and =55 years (group C, n=68). Low exposure groups lived further away from the complex with lower urinary levels of V and 1-OHP, matched to high exposure groups by age 9-15 (group B, n=66) and =55years (group D, n=68). Urine metabolomes were analyzed following Nature protocol using 2 dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS). 3 online databases were used for characterization: Chemical Entities of Biological Interest (ChEBI), Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Human Metabolome Database (HMDB). Partial least-squares-discriminant analysis (PLS-DA) was used to find metabolic changes between exposure groups. Results: GCxGC-TOFMS extracted 478 peaks. PLS-DA examined metabolic profile variances and found clear separation between exposure groups. On the basis of the variable importance in the projection threshold (VIP=1) and p

Clinical and demographic factors associated with compliance and subsequent urinary metabolic changes in first-time ureteral stone formers

Dietary and lifestyle modifications are widely prescribed to prevent recurrence of urolithiasis, although little is known about the clinical and demographic factors associated with patient compliance and urinary metabolic changes. The present study assessed the clinical and demographic factors influencing compliance with a modified diet and lifestyle in first-time ureteric stone formers as well as determined the effects of compliance on urinary stone risk factors. We retrospectively reviewed the medical records of 53 patients presenting with ureteric calcium stones. Using a self-completed questionnaire, patients were classified according to compliance with seven recommendations for modifying diet and lifestyle into good compliance group (complied with ≥ three recommendations) and poor compliance group. Before (on a random diet) and after prescribing the modifications, 24 hour urine samples were collected from those in the good and poor compliance group. The stone size at presentation and initial treatment modality were closely associated with patient compliance (P=0.019, P=0.027, respectively). Citrate excretion significantly increased in the good compliance group after adopting modifications (P=0.012), whereas the poor compliance group did not show a statistically significant difference. Moreover, patients in the poor compliance group showed significantly increased urinary calcium excretion by the end of the study (P=0.040). After adjustments for age, sex, body mass index, and metabolic abnormality status, poor compliance was found to be an independent risk factor for persistence or development of hypocitraturia (OR: 3.885; 95% CI: 1.102~13.694; P=0.035). In conclusion, our results imply that patient education programs regarding diet and lifestyle should be tailored to the individual’s clinical and demographic characteristics.

Identifying early urinary metabolic changes with long-term environmental exposure to cadmium by mass-spectrometry-based metabolomics.

Cadmium (Cd) is a common environmental pollutant, and urinary Cd (UCd) is generally used as a marker of exposure; however, our understanding on the related urinary metabolic changes caused by Cd exposure is still not clear. In this study, we applied a mass-spectrometry-based metabolomic approach to assess the urinary metabolic changes in human with long-term environmental Cd exposure, aimed to identify early biomarkers to assess Cd nephrotoxicity. Urine samples from 94 female never smokers aged 44-70 with UCd in the range of 0.20-68.67 μg/L were analyzed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-ToF-MS) and gas chromatography-mass spectrometry (GC-MS). It was found that metabolites related to amino acid metabolism (L-glutamine, L-cystine, L-tyrosine, N-methyl-L-histidine, L-histidinol, taurine, phenylacetylglutamine, hippurate, and pyroglutamic acid), galactose metabolism (D-galactose and myo-inositol), purine metabolism (xanthine, urea, and deoxyadenosine monophosphate), creatine pathway (creatine and creatinine), and steroid hormone biosynthesis (17-α-hydroxyprogesterone, tetrahydrocortisone, estrone, and corticosterone) were significantly higher among those with a UCd level higher than 5 μg/L. Moreover, we noticed that the level of N-methyl-L-histidine had already started to elevate among individuals with a UCd concentration of ≥2 μg/L. The overall findings illustrate that metabolomics offer a useful approach for revealing metabolic changes as a result of Cd exposure.

Urinary metabolomic changes as a predictive biomarker of asthma exacerbation

Urinary metabolomic changes as a predictive biomarker of asthma exacerbation

Urinary Cadmium as a Marker of Exposure in Epidemiological Studies

Urinary cadmium (U-Cd) is commonly interpreted in epidemiological studies to measure cadmium accumulated in the kidney, and is thus used as a marker of long-term exposure. This concept is based primarily on occupational cohorts exposed to high Cd levels, and its generalization to populations chronically exposed to lower environmental Cd levels—primarily through tobacco and foods grown on contaminated soil—is of central importance to studies of health outcomes, including heart disease, cancer, kidney disease, and osteoporosis, that have been associated with Cd (Jarup and Akesson 2009). In their article, Chaumont et al. (2013) described complications with understanding Cd body burden from U-Cd. However, several items in the article would benefit from clarification. Evidence presented by Chaumont et al. (2013) included stratified plots of log-transformed U-Cd with age, comparing men and women and, separately, by smoking status. The authors observed an approximately constant offset between current smokers and nonsmokers, which they interpreted to mean that the difference in U-Cd did not change with age—in contrast to the expectation based on U-Cd reflecting accumulation of Cd in the kidney. However, a constant offset between curves on a log-scale implies that the ratio, not the difference, is constant. Because the curves have generally upward trends, the difference in U-Cd between current smokers and nonsmokers must be increasing. Furthermore, Figure 2 and Table 2 of Chaumont et al. (2013) showed higher mean U-Cd in former smokers compared with never-smokers over a range of ages, as expected if U-Cd reflects, at least in part, cumulative exposure. Nonetheless the authors stated, “We observed no differences … between former and never-smoker adults.” The difference did not reach statistical significance, which might be explained by the modest sample size and broad distribution of U-Cd in former smokers, who were more often male than never-smokers and who may have varied widely in smoking dose and may have quit smoking years before the study. A more informative investigation of the association of U-Cd with smoking would use multivariate regression, controlling for these variables. Many studies from a variety of populations have demonstrated higher U-Cd in former smokers (Adams and Newcomb 2013; Adams et al. 2011; Gunier et al. 2013; McElroy et al. 2007; Olsson et al. 2002; Paschal et al. 2000). Chaumont et al. (2013) concluded that estimates of dietary Cd intake from food contamination data might be more useful than U-Cd for exposure assessment. It seems unlikely that individual-level exposure measurement based on dietary recall would be superior to measurement of U-Cd whether U-Cd reflects long-term or recent exposure, or a combination. Chaumont et al. (2013) highlighted the importance of carefully considering human Cd physiology, particularly in children and adolescents. Clearly the relationship between U-Cd and Cd exposure is complex. Yet the results of Chaumont et al. do not warrant abandonment of U-Cd as a measure of environmental exposure for epidemiological studies.

Metabolic changes in urine during and after pregnancy in a large, multiethnic population-based cohort study of gestational diabetes.

This study aims to identify novel markers for gestational diabetes (GDM) in the biochemical profile of maternal urine using NMR metabolomics. It also catalogs the general effects of pregnancy and delivery on the urine profile. Urine samples were collected at three time points (visit V1: gestational week 8–20; V2: week 28±2; V3∶10–16 weeks post partum) from participants in the STORK Groruddalen program, a prospective, multiethnic cohort study of 823 healthy, pregnant women in Oslo, Norway, and analyzed using 1H-NMR spectroscopy. Metabolites were identified and quantified where possible. PCA, PLS-DA and univariate statistics were applied and found substantial differences between the time points, dominated by a steady increase of urinary lactose concentrations, and an increase during pregnancy and subsequent dramatic reduction of several unidentified NMR signals between 0.5 and 1.1 ppm. Multivariate methods could not reliably identify GDM cases based on the WHO or graded criteria based on IADPSG definitions, indicating that the pattern of urinary metabolites above micromolar concentrations is not influenced strongly and consistently enough by the disease. However, univariate analysis suggests elevated mean citrate concentrations with increasing hyperglycemia. Multivariate classification with respect to ethnic background produced weak but statistically significant models. These results suggest that although NMR-based metabolomics can monitor changes in the urinary excretion profile of pregnant women, it may not be a prudent choice for the study of GDM.

1H-NMR-based metabonomic analysis of metabolic profiling in diabetic nephropathy rats induced by streptozotocin

Elucidation of the metabolic profiling in diabetic nephropathy (DN) rats is of great assistance for understanding the pathogenesis of DN. In this study, ¹H-nuclear magnetic resonance (NMR)-based metabonomics combined with HPLC measurements was used to quantitatively analyze the metabolic changes in urine and kidney extracts from diabetic 2-wk and 8-wk rats induced by streptozotocin (STZ). Pattern recognition analysis of either urine or kidney extracts indicated that the two diabetic groups were separated obviously from the control group, suggesting that the metabolic profiles of the diabetic groups were markedly different from the control. The diabetic 8-wk rats showed lower levels of creatine, dimethylamine, and higher levels of ascorbate, succinate, lactate, citrate, allantoin, 2-ketoglutarate, and 3-hydrobutyrate (3-HB) in the urine samples. Moreover, the diabetic 8-wk rats displayed lower levels of succinate, creatine, myo-inositol, alanine, lactate, and ATP, and higher levels of 3-HB and glucose in the kidney extracts. The observed metabolic changes imply the enhanced pathways of either lipid or ketone body synthesis and decreased pathways of either tricarboxylic acid cycle or glycolysis in DN rats compared with the control. Our results suggest that the energy metabolic changes are associated with the pathogenic process of DN.

TH‐D‐201C‐09: Evaluation of Metabolomics Data Using Univariate and Multivariate Statistical Analysis Techniques

Purpose: To quantify urinary metabolic changes in experimental animals as they transitioned from healthy to tumor bearing. Univariate and multivariate statistical tests were used to identify patterns of metabolic behaviour that changed in a significant manner. Receiver operator characteristic (ROC) curve analysis was used to evaluate the utility of the tests. Method and Materials: Human GBM cells were grown as xenografts in NIH iii nude mice at 6 weeks of age. Urine samples were collected daily beginning one week prior to cell injections and lasting four weeks after injection. Selected samples were run on an Oxford 800MHz cold probe NMR Spectrometer (Oxford England) utilizing a 1‐D NOESY pulse sequence. The acquired spectra were analyzed by targeted profiling using Chenomx Suite 5.1 (Chenomx Inc Edmonton Canada). The paired t‐test was used to evaluate changes in metabolite concentrations in the pre‐injection population compared to the post‐injection population. The same test was also applied to metabolite ratios. Principal component analysis (PCA) and partial least squares discriminant analysis (PDS‐DA) were used to search for more complicated relationships in the data. Results: Application of the t‐test to the ratios of metabolites revealed 20 ratios that were significant beyond the Bonferroni correction threshold and 152 more ratios were significant under the FDR condition. Of the significant ratios 7 had an AUC greater than 0.9 and 68 had an AUC between 0.8 and 0.9. After correcting for changes found in the control animals 12 and 36 ratios that satisfied the Bonferroni and FDR thresholds respectively. 6 ratios had an AUC exceeding 0.9 and a further 16 having an AUC greater than 0.8. Conclusion: Metabolic profiling of urine samples in animal models demonstrates that this technique has the potential to serve as a screening tool for certain types of cancers.

Changes of metabolic profiles in urine after oral administration of quercetin in rats

Quercetin has been studied extensively. However, its actions in vivo are not well understood. We investigated the overall metabolic changes in urine after oral quercetin administration in rats and try to provide useful information on the actions of quercetin in vivo. Rats were orally administered a single dose of quercetin aglycon (40mg/kg body weight). Urine samples were collected and subjected to 1H nuclear magnetic resonance (NMR)-based metabolomic analysis and high performance liquid chromatography–mass spectrometry (HPLC–MS). Significant changes of metabolic profiles were observed in urine after quercetin administration. Relative increase in the concentrations of choline, creatinine, dimethylglycine, hippurate, taurine, trimethylamine N-oxide and reduction in acetate, alanine, lactate were observed. The concentrations of citrate, 2-oxoglutarate and succinate increased in the 0–24h period after treatment and decreased thereafter. Some peaks assignable to quercetin metabolites were found in the aromatic regions of 1H NMR spectra. HPLC–MS analysis identified quercetin, methyl quercetin, quercetin sulfate, quercetin monoglucuronide, and methyl quercetin monoglucuronide in urine after administration of quercetin. Our current findings indicate that quercetin behaves not only as an antioxidant, but also a modulator for some metabolic processes in vivo. The active forms of quercetin present in the biofluids must be investigated further.

A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human

Type 2 diabetes mellitus is the result of a combination of impaired insulin secretion with reduced insulin sensitivity of target tissues. There are an estimated 150 million affected individuals worldwide, of whom a large proportion remains undiagnosed because of a lack of specific symptoms early in this disorder and inadequate diagnostics. In this study, NMR-based metabolomic analysis in conjunction with multivariate statistics was applied to examine the urinary metabolic changes in two rodent models of type 2 diabetes mellitus as well as unmedicated human sufferers. The db/db mouse and obese Zucker (fa/fa) rat have autosomal recessive defects in the leptin receptor gene, causing type 2 diabetes. 1H-NMR spectra of urine were used in conjunction with uni- and multivariate statistics to identify disease-related metabolic changes in these two animal models and human sufferers. This study demonstrates metabolic similarities between the three species examined, including metabolic responses associated with general systemic stress, changes in the TCA cycle, and perturbations in nucleotide metabolism and in methylamine metabolism. All three species demonstrated profound changes in nucleotide metabolism, including that of N-methylnicotinamide and N-methyl-2-pyridone-5-carboxamide, which may provide unique biomarkers for following type 2 diabetes mellitus progression.

Vanillactic acid in the urine of melanoma patients

Arsenic exposure is considered a major environmental threat to human health. It is already known that high-level arsenic exposure has adverse effects on human health. Since the pregnant women are known to be more susceptible to some chemical exposures than ordinary people, the understanding regarding the health effects of low-level arsenic exposure on pregnant women is critical and remains unclear. The aim of this study is to investigate the urinary metabolic changes of pregnant women exposed to low-dose arsenic, and to identify biomarkers from metabolomics analysis. Urine samples of 246 pregnant women were collected in the first trimester of pregnancy and were divided into three groups based on the tertile distribution of urinary arsenic concentrations which were determined using inductively coupled plasma mass spectrometry (ICP-MS). Changes in the metabolite profile were measured using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS). Arsenic- related metabolic biomarkers were investigated by comparing the samples of the first and third tertiles of arsenic exposure classifications using a partial least-squares discriminant model (PLS-DA). Nine urine potential biomarkers were putatively identified, including LysoPC (14:0), glutathione, 18-carboxy-dinor-LTE4, 20-COOH-LTE4, cystathionine ketimin, 1-(beta-d-ribofuranosyl)-1,4-dihydronicotinamide, thiocysteine, p-cresol glucuronide and vanillactic acid. The obtained results showed that environmental arsenic exposure, even at low levels, could cause metabolite alterations in pregnant women which might be associated with adverse health outcomes. This is the first report on metabolic changes in pregnant women for arsenic exposure. The findings may be valuable for the arsenic risk assessment for pregnant women.