Abstract

C-Mannosyl tryptophan (CMW) is a unique glycosylated amino acid, and a candidate novel biomarker of renal function. In type 2 diabetes (T2D), a combination of metabolites including CMW has recently been the focus of novel biomarkers for the evaluation of renal function and prediction of its decline. However, previous quantification methods for serum CMW have several limitations. We recently established a novel assay for quantifying serum CMW. Serum CMW from 99 Japanese patients with T2D was quantified by this assay using hydrophilic interaction liquid chromatography. The serum CMW levels were cross-sectionally characterized in relation to clinical features, including renal function and vascular complications. Serum CMW level was more strongly correlated with serum creatinine and cystatin C levels and with eGFR than with albumin urea level. The ROC curve to detect eGFR < 60 ml/min/1.73 m2 revealed that the cutoff serum CMW level was 337.5 nM (AUC 0.883). Serum CMW levels were higher in patients with a history of macroangiopathy than in those without history. They correlated with ankle-brachial pressure index, whereas cystatin C did not. Serum CMW levels quantified by the novel assay could be useful in evaluation of glomerular filtration of renal function and peripheral arterial disease in T2D.

Highlights

  • C-Mannosyl tryptophan (CMW) is a unique glycosylated amino acid, which is composed by linking a monosaccharide, mannose and an aromatic amino acid, Trp, through a C–C ­bond[1]

  • Quantification of estimated glomerular filtration rate (eGFR) based on those two markers is strongly recommended in several guidelines for assessment of renal function in relation to diabetic nephropathy, which is necessary to confirm the stage of ­CKD13,14

  • The precision and accuracy of the assay were expressed as the relative standard deviation (RSD) (%) and the relative error (RE) (%), respectively, and the lower limit of quantification (LLOQ) was within ± 20%, and the other quality control (QC) levels were all within ± 15% for the nominal analytes (Table 1)

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Summary

Introduction

C-Mannosyl tryptophan (CMW) is a unique glycosylated amino acid, which is composed by linking a monosaccharide, mannose and an aromatic amino acid, Trp, through a C–C ­bond[1]. Quantification of eGFRs based on those two markers is strongly recommended in several guidelines for assessment of renal function in relation to diabetic nephropathy, which is necessary to confirm the stage of ­CKD13,14. These biomarkers still have several l­imitations[12,15]. We first quantified serum CMW levels by the novel assay and characterized them in relation to the clinical characteristics including present biomarkers for renal function in patients with type 2 diabetes (T2D). We investigated the clinical advantage of quantifying the absolute value of CMW beyond the assessment of renal function

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