MO635: Early Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients is Associated with A Particular Ganglioside Profile, Identified by High-Resolution Tandem Mass Spectrometry:A Pilot Study

Autor: Anca Suteanu-Simulescu, Raluca Ica, Mirela Sarbu, Cristian Munteanu, Florica Gadalean, Adrian Vlad, Silvia Velciov, Cristina Anca Gluhovschi, Flaviu Bob, Catalin Jianu, Octavian Cretu, Livia Oana Milas, Maria Mogos, Mihaela Patruica, Balint Lavinia, Ienciu Silvia, Alina Diana Zamfir, Ligia Petrica
Rok vydání: 2022
Předmět:
Zdroj: Nephrology Dialysis Transplantation. 37
ISSN: 1460-2385
0931-0509
DOI: 10.1093/ndt/gfac076.028
Popis: BACKGROUND AND AIMS Metabolic biomarkers are of high importance for the identification of early renal involvement in the course of type 2 diabetes mellitus (DM). Gangliosides, which are complex cell type-specific glycosphingolipids, consist of a sialylated oligosaccharide chain attached to a ceramide of different composition with respect to the sphingoid base and fatty acid residues [1]. Gangliosides play a major role in the pathogenesis of diabetic kidney disease (DKD). The aim of the study was to assess the pattern of urinary gangliosides in patients with type 2 DM. METHOD The urine gangliosidome of 30 type 2 DM patients (10 normo-, 10 micro-, and 10 macroalbuminuric) has been investigated in a cross-sectional pilot study, by a comparative assay with 10 healthy controls. Following the optimization of urine ganglioside extraction procedure [2, 3], we have determined the composition of native ganglioside mixtures from the 24-h collected urine samples using a modern bioanalytical platform based on nanoelectrospray ionization (nanoESI) high-resolution mass spectrometry (HR MS) on an Orbitrap instrument. RESULTS HR MS screening and fragmentation analysis by tandem MS revealed that: (i) the urinary gangliosidome of type 2 DM patients contains a significantly higher number of distinct species differing in either their glycan or ceramide structure than the controls; (ii) the ganglioside urinary level was significantly increased in normoalbuminuric patients compared with healthy control subjects; (iii) the gangliosidome of macroalbuminuric patients is characterized by an elevated overall sialic acid content than normo- and microalbuminuric diabetics and more complex structures, including fucosylated, O-GalNAc- and CH3COO--modified compounds; (iv) the degree of sialylation of species presented correlations with the level of albuminuria and renal function; (v) further detailed structural analysis of a type GQ1(d18:1/18:0) species (identified only in macroalbuminuric patients) demonstrated that the present isomer is of type D (all four syalic acids are linked to the inner galactose). CONCLUSION HR MS by tandem MS methods, using an Orbitrap instrument, are a reliable tool for the identification of a particular ganglioside profile in the urine of type 2 DM patients. The sialylated species and those altered by peripheral attachments to the glycan core might be considered useful indicators of early DKD.
Databáze: OpenAIRE
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