Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy

Abstract

Capillary electrophoresis coupled with time-of-flight mass spectrometry was used to explore new serum biomarkers with high sensitivity and specificity for diabetic nephropathy (DN) diagnosis, through comprehensive analysis of serum metabolites with 78 diabetic patients. Multivariate analyses were used for identification of marker candidates and development of discriminative models. Of the 289 profiled metabolites, orthogonal partial least-squares discriminant analysis identified 19 metabolites that could distinguish between DN with macroalbuminuria and diabetic patients without albuminuria. These identified metabolites included creatinine, aspartic acid, γ-butyrobetaine, citrulline, symmetric dimethylarginine (SDMA), kynurenine, azelaic acid, and galactaric acid. Significant correlations between all these metabolites and urinary albumin-to-creatinine ratios (p < 0.009, Spearman's rank test) were observed. When five metabolites (including γ-butyrobetaine, SDMA, azelaic acid and two unknowns) were selected from 19 metabolites and applied for multiple logistic regression model, AUC value for diagnosing DN was 0.927 using the whole dataset, and 0.880 in a cross-validation test. In addition, when four known metabolites (aspartic acid, SDMA, azelaic acid and galactaric acid) were applied, the resulting AUC was still high at 0.844 with the whole dataset and 0.792 with cross-validation. Combination of serum metabolomics with multivariate analyses enabled accurate discrimination of DN patients. The results suggest that capillary electrophoresis-mass spectrometry based metabolome analysis could be used for DN diagnosis.

Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol

“…Dried aqueous metabolites were reconstituted with 50 ml of Milli-Q water that contained two reference compounds (200 mM each of 3-aminopyrrolidine and trimesic acid). Samples were analysed using capillary electrophoresis-electrospray ionization (ESI)-time-of-flight mass spectrometry (TOFMS) in both positive and negative mode 39 . In brief, cationic metabolites were separated in a fused silica capillary (50 mm i.d.…”

Systems biology analysis reveals role of MDM2 in diabetic nephropathy

“…On the contrary, metabolites are the final product of cellular processes, providing a direct link to phenotypes (1). For this reason, an increasing number of studies have been conducted to discover metabolites whose levels significantly change in a specific clinical condition (2)(3)(4). In a previous study, we identified a panel of 13 metabolites that were robustly altered in patients with diabetic nephropathy (3), thus motivating us to investigate the underlying molecular networks linked to these metabolites.…”

Capillary electrophoresis mass spectrometry based metabolomics

“…Importantly, CE also gives complementary information to HILIC [13], as well as, significantly better peak shape in many cases. It is therefore not surprising that CE-MS has already been considered for multiple metabolomics studies covering several applications, from aging [19], amino acid analysis [20,21] [46][47][48][49][50][51][52][53], CVD [54][55][56][57][58], diabetes [59][60][61][62][63][64][65], lifestyle [61][62][63][64][65][66][67][68][69][70][71], kidney disease [72,73], liver disease [74][75][76][77][78][79][80][81][82], the microbiome [83][84]…”