High-Resolution Tandem Mass Spectrometry Identifies a Particular Ganglioside Pattern in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus Patients
Anca Suteanu-Simulescu,
Alina Diana Zamfir,
Raluca Ica,
Mirela Sarbu,
Cristian V. A. Munteanu,
Florica Gadalean,
Adrian Vlad,
Flaviu Bob,
Dragos Catalin Jianu,
Ligia Petrica
Affiliations
Anca Suteanu-Simulescu
Department of Internal Medicine II, Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
Alina Diana Zamfir
Department of Condensed Matter, National Institute for Research and Development in Electrochemistry and Condensed Matter, 300569 Timisoara, Romania
Raluca Ica
Department of Condensed Matter, National Institute for Research and Development in Electrochemistry and Condensed Matter, 300569 Timisoara, Romania
Mirela Sarbu
Department of Condensed Matter, National Institute for Research and Development in Electrochemistry and Condensed Matter, 300569 Timisoara, Romania
Cristian V. A. Munteanu
Department of Bioinformatics & Structural Biochemistry, Institute of Biochemistry, 060031 Bucharest, Romania
Florica Gadalean
Department of Internal Medicine II, Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
Adrian Vlad
Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania
Flaviu Bob
Department of Internal Medicine II, Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
Dragos Catalin Jianu
Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania
Ligia Petrica
Department of Internal Medicine II, Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
Considering the valuable information provided by glycosphingolipids as molecular markers and the limited data available for their detection and characterization in patients suffering from Type 2 diabetic kidney disease (DKD), we developed and implemented a superior method based on high-resolution (HR) mass spectrometry (MS) and tandem MS (MS/MS) for the determination of gangliosides in the urine of DKD patients. This study was focused on: (i) testing of the HR MS and MS/MS feasibility and performances in mapping and sequencing of renal gangliosides in Type 2 DM patients; (ii) determination of the changes in the urine gangliosidome of DKD patients in different stages of the disease—normo-, micro-, and macroalbuminuria—in a comparative assay with healthy controls. Due to the high resolution and mass accuracy, the comparative MS screening revealed that the sialylation status of the ganglioside components; their modification by O-acetyl, CH3COO−, O-fucosyl, and O-GalNAc; as well as the composition of the ceramide represent possible markers for early DKD detection, the assessment of disease progression, and follow-up treatment. Moreover, structural investigation by MS/MS demonstrated that GQ1d(d18:1/18:0), GT1α(d18:1/18:0) and GT1b(d18:1/18:0) isomers are associated with macroalbuminuria, meriting further investigation in relation to their role in DKD.