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A high-performance liquid chromatography-tandem mass spectrometry-based targeted metabolomics kidney dysfunction marker panel in human urine.

ABSTRACT: Previous studies have examined and documented fluctuations in urine metabolites in response to disease processes and drug toxicity affecting glomerular filtration, tubule cell metabolism, reabsorption, oxidative stress, purine degradation, active secretion and kidney amino acylase activity representative of diminished renal function. However, a high-throughput assay that incorporates metabolites that are surrogate markers for such changes into a kidney dysfunction panel has yet to be described.A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay for the quantification of ten metabolites associated with the Krebs cycle, purine degradation, and oxidative stress in human urine was developed and validated. Normal values were assessed in healthy adult (n=120) and pediatric (n=36) individuals. In addition, 9 pediatric renal transplant recipients patients were evaluated before and after initial dosing of the immunosuppressant tacrolimus in a proof-of-concept study.The assay met all predefined acceptance criteria. The lower limit of quantification ranged from 0.1 to 1000 ?mol/l. Inter-day trueness and imprecisions ranged from 91.4-112.9% and 1.5-12.4%, respectively. The total assay run time was 5.5 minutes. Concentrations of glucose, sorbitol, and trimethylamine oxide (TMAO) were elevated in pediatric renal transplant patients (n=9) prior to transplantation as well as before and immediately after initial dosing of tacrolimus. One month post-transplant urine metabolite patterns matched those of healthy children (n=36).The LC-MS/MS assay will provide the basis for further large-scale clinical studies to explore these analytes as molecular markers for the patients with renal insufficiency.

SUBMITTER: Klepacki J

PROVIDER: S-EPMC6028022 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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A high-performance liquid chromatography-tandem mass spectrometry-based targeted metabolomics kidney dysfunction marker panel in human urine.

Klepacki Jacek J Klawitter Jost J Klawitter Jelena J Thurman Joshua M JM Christians Uwe U

Clinica chimica acta; international journal of clinical chemistry 20150411

<h4>Background</h4>Previous studies have examined and documented fluctuations in urine metabolites in response to disease processes and drug toxicity affecting glomerular filtration, tubule cell metabolism, reabsorption, oxidative stress, purine degradation, active secretion and kidney amino acylase activity representative of diminished renal function. However, a high-throughput assay that incorporates metabolites that are surrogate markers for such changes into a kidney dysfunction panel has ye ...[more]

PMID: 25871999

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Project description:Both obesity and the metabolic syndrome are risk factors for type 2 diabetes and cardiovascular disease. Identification of novel biomarkers are needed to distinguish metabolic syndrome from equally obese individuals in order to direct them to early interventions that reduce their risk of developing further health problems. We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established metabolic syndrome criteria (i.e. elevated waist circumference, hypertension, elevated fasting glucose, elevated triglycerides, and low high-density lipoprotein cholesterol) in plasma samples from obese men ( n = 29; BMI = 35.5 ± 5.2 kg/m2) and women ( n = 40; 34.9 ± 6.7 kg/m2), of which 26 met the criteria for metabolic syndrome (17 men and 9 women). Compared to obese individuals without metabolic syndrome, univariate statistical analysis and partial least squares discriminant analysis showed that a specific group of metabolites from multiple metabolic pathways (i.e. purine metabolism, valine, leucine and isoleucine degradation, and tryptophan metabolism) were associated with the presence of metabolic syndrome. Receiver operating characteristic curves generated based on the PLS-DA models showed excellent areas under the curve (0.85 and 0.96, for metabolites only model and enhanced metabolites model, respectively), high specificities (0.86 and 0.93), and good sensitivities (0.71 and 0.91). Moreover, principal component analysis revealed that metabolic profiles can be used to further differentiate metabolic syndrome with 3 versus 4-5 metabolic syndrome criteria. Collectively, these findings support targeted metabolomics approaches to distinguish metabolic syndrome from obesity alone, and to stratify metabolic syndrome status based on the number of criteria met. Impact statement We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established MetS criteria. To our best knowledge, the findings of this study provide the first evidence that metabolic profiles can be used to differentiate participants with MetS from similarly obese individuals who do not meet established criteria of MetS. Furthermore, the study demonstrated that within MetS participants, their unique metabolic profiles correlated to the number of criteria used for MetS determination. Taken together, this metabolic profiling approach can potentially serve as a novel tool for MetS detection and monitoring, and provide useful metabolic information for future interventions targeting obesity and MetS.

Dataset Information

A high-performance liquid chromatography-tandem mass spectrometry-based targeted metabolomics kidney dysfunction marker panel in human urine.

Publications

A high-performance liquid chromatography-tandem mass spectrometry-based targeted metabolomics kidney dysfunction marker panel in human urine.

Similar Datasets

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