Untargeted Metabolomics by Ultra-High-Performance Liquid Chromatography Coupled with Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometry Analysis Identifies a Specific Metabolomic Profile in Patients with Early Chronic Kidney Disease

Author:

Glavan Mihaela-Roxana12,Socaciu Carmen3ORCID,Socaciu Andreea Iulia4,Gadalean Florica12,Cretu Octavian M.5,Vlad Adrian6ORCID,Muntean Danina M.78,Bob Flaviu12,Milas Oana12,Suteanu Anca12ORCID,Jianu Dragos Catalin910,Stefan Maria12,Balint Lavinia12,Ienciu Silvia12,Petrica Ligia12ORCID

Affiliation:

1. Department of Internal Medicine II—Nephrology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania

2. Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania

3. Research Center for Applied Biotechnology and Molecular Therapy BIODIATECH, SC Proplanta, 400478 Cluj-Napoca, Romania

4. Department of Occupational Health, University of Medicine and Pharmacy “Iuliu Haţieganu”, 400347 Cluj-Napoca, Romania

5. Department of Surgery—Surgical Semiotics, “Victor Babeş” University of Medicine and Pharmacy, 300041 Timişoara, Romania

6. Department of Internal Medicine II—Diabetes and Metabolic Diseases, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania

7. Department of Functional Sciences—Pathophysiology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania

8. Center for Translational Research and Systems Medicine, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania

9. Deptartment of Neurosciences—Neurology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania

10. Centre for Cognitive Research in Neuropsychiatric Pathology, Clinical County Emergency Hospital, Victor Babeș” University of Medicine and Pharmacy, 300723 Timișoara, Romania

Abstract

Chronic kidney disease (CKD) has emerged as one of the most progressive diseases with increased mortality and morbidity. Metabolomics offers new insights into CKD pathogenesis and the discovery of new biomarkers for the early diagnosis of CKD. The aim of this cross-sectional study was to assess metabolomic profiling of serum and urine samples obtained from CKD patients. Untargeted metabolomics followed by multivariate and univariate analysis of blood and urine samples from 88 patients with CKD, staged by estimated glomerular filtration rate (eGFR), and 20 healthy control subjects was performed using ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry. Serum levels of Oleoyl glycine, alpha-lipoic acid, Propylthiouracil, and L-cysteine correlated directly with eGFR. Negative correlations were observed between serum 5-Hydroxyindoleacetic acid, Phenylalanine, Pyridoxamine, Cysteinyl glycine, Propenoylcarnitine, Uridine, and All-trans retinoic acid levels and eGFR. In urine samples, the majority of molecules were increased in patients with advanced CKD as compared with early CKD patients and controls. Amino acids, antioxidants, uremic toxins, acylcarnitines, and tryptophane metabolites were found in all CKD stages. Their dual variations in serum and urine may explain their impact on both glomerular and tubular structures, even in the early stages of CKD. Patients with CKD display a specific metabolomic profile. Since this paper represents a pilot study, future research is needed to confirm our findings that metabolites can serve as indicators of early CKD.

Funder

“Victor Babeș” University of Medicine and Pharmacy, Faculty of Medicine, Timișoara, Romania

Centre for Molecular Research in Nephrology and Vascular Disease, “Victor Babeș” University of Medicine and Pharmacy, Faculty of Medicine, Timișoara, Romania

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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