Quantitative, Targeted Analysis of Gut Microbiota Derived Metabolites Provides Novel Biomarkers of Early Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients
Lavinia Balint,
Carmen Socaciu,
Andreea Iulia Socaciu,
Adrian Vlad,
Florica Gadalean,
Flaviu Bob,
Oana Milas,
Octavian Marius Cretu,
Anca Suteanu-Simulescu,
Mihaela Glavan,
Silvia Ienciu,
Maria Mogos,
Dragos Catalin Jianu,
Ligia Petrica
Affiliations
Lavinia Balint
Department of Internal Medicine II—Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, County Emergency Hospital, 300041 Timisoara, Romania
Carmen Socaciu
Center for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania
Andreea Iulia Socaciu
Department of Occupational Health, University of Medicine and Pharmacy “Iuliu Haţieganu”, Victor Babes 8, 400347 Cluj-Napoca, Romania
Adrian Vlad
Center for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania
Florica Gadalean
Department of Internal Medicine II—Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, County Emergency Hospital, 300041 Timisoara, Romania
Flaviu Bob
Department of Internal Medicine II—Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, County Emergency Hospital, 300041 Timisoara, Romania
Oana Milas
Department of Internal Medicine II—Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, County Emergency Hospital, 300041 Timisoara, Romania
Octavian Marius Cretu
Department of Surgery I—Division of Surgical Semiology I, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, Emergency Clinical Municipal Hospital, 300041 Timisoara, Romania
Anca Suteanu-Simulescu
Department of Internal Medicine II—Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, County Emergency Hospital, 300041 Timisoara, Romania
Mihaela Glavan
Department of Internal Medicine II—Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, County Emergency Hospital, 300041 Timisoara, Romania
Silvia Ienciu
Department of Internal Medicine II—Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, County Emergency Hospital, 300041 Timisoara, Romania
Maria Mogos
Department of Internal Medicine II—Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, County Emergency Hospital, 300041 Timisoara, Romania
Dragos Catalin Jianu
Center for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania
Ligia Petrica
Department of Internal Medicine II—Division of Nephrology, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, County Emergency Hospital, 300041 Timisoara, Romania
Diabetic kidney disease (DKD) is one of the most debilitating complications of type 2 diabetes mellitus (T2DM), as it progresses silently to end-stage renal disease (ESRD). The discovery of novel biomarkers of early DKD becomes acute, as its incidence is reaching catastrophic proportions. Our study aimed to quantify previously identified metabolites from serum and urine through untargeted ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques, such as the following: arginine, dimethylarginine, hippuric acid, indoxyl sulfate, p-cresyl sulfate, L-acetylcarnitine, butenoylcarnitine and sorbitol. The study concept was based on the targeted analysis of selected metabolites, using the serum and urine of 20 healthy subjects and 90 T2DM patients with DKD in different stages (normoalbuminuria—uACR 300 mg/g). The quantitative evaluation of metabolites was performed with pure standards, followed by the validation methods such as the limit of detection (LOD) and the limit of quantification (LOQ). The following metabolites from this study resulted as possible biomarkers of early DKD: in serum—arginine, dimethylarginine, hippuric acid, indoxyl sulfate, butenoylcarnitine and sorbitol and in urine—p-cresyl sulfate.