Diminished Systemic Amino Acids Metabolome and Lipid Peroxidation in Ureteropelvic Junction Obstruction (UPJO) Infants Requiring Surgery

Olga Begou; Antigoni Pavlaki; Olga Deda; Alexander Bollenbach; Kathrin Drabert; Helen Gika; Evangelia Farmaki; John Dotis; Nikoleta Printza; Georgios Theodoridis; Dimitrios Tsikas

doi:10.3390/jcm10071467

Diminished Systemic Amino Acids Metabolome and Lipid Peroxidation in Ureteropelvic Junction Obstruction (UPJO) Infants Requiring Surgery

J Clin Med. 2021 Apr 2;10(7):1467. doi: 10.3390/jcm10071467.

Authors

Olga Begou^{1

2

3}, Antigoni Pavlaki⁴, Olga Deda^{2

5}, Alexander Bollenbach³, Kathrin Drabert³, Helen Gika^{2

5}, Evangelia Farmaki⁶, John Dotis⁴, Nikoleta Printza⁴, Georgios Theodoridis^{1

2}, Dimitrios Tsikas³

Affiliations

¹ Laboratory of Analytical Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
² Biomic_AUTh, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center, B1.4, 10th km Thessaloniki-Thermi Rd, P.O. Box 8318, 57001 Thessaloniki, Greece.
³ Core Unit Proteomics, Hannover Medical School, Institute of Toxicology, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
⁴ Paediatric Nephrology Unit, First Department of Paediatrics, Hippokratio Hospital, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
⁵ Laboratory of Forensic Medicine and Toxicology, School of Medicine, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
⁶ Paediatric Immunology and Rheumatology Referral Center, First Department of Paediatrics, Hippokratio Hospital, University Campus, 54124 Thessaloniki, Greece.

Abstract

Congenital anomalies of the urinary tract, and particularly of obstructive nephropathy such as ureteropelvic junction obstruction (UPJO) in infants, can later lead to chronic kidney disease and hypertension. Fundamental questions regarding underlying mechanisms remain unanswered. The aim of the present study was to quantitate the systemic amino acids metabolome in 21 UPJO infants requiring surgery (Group A) and 21 UPJO infants under conservative treatment (Group B). Nineteen healthy age-matched infants served as controls (Group C). Serum amino acids involved in several pathways and representative metabolites, including the L-arginine-derived nitric oxide (NO) metabolites nitrite and nitrate and the lipid peroxidation biomarker malondialdehyde (MDA) were measured by gas chromatography-mass spectrometry (GC-MS) methods using their stable-isotope labeled analogs as internal standards after derivatization to their methyl esters N-pentafluoropropionic amides (amino acids) and to their pentafluorobenzyl derivatives (nitrite, nitrate, MDA). The concentrations of the majority of the biomarkers were found to be lower in Group A compared to Group B. Statistical analysis revealed clear differentiation between the examined study groups. Univariate statistical analysis highlighted serum homoarginine (q = 0.006), asymmetric dimethylarginine (q = 0.05) and malondialdehyde (q = 0.022) as potential biomarkers for UPJO infants requiring surgery. Group A also differed from Group B with respect to the diameter of the preoperative anterior-posterior renal pelvis (AP) as well as regarding the number and extent of inverse correlations between AP and the serum concentrations of the biomarkers. In Group A, but not in Group B, the AP diameter strongly correlated with hydroxy-proline (r = -0.746, p = 0.0002) and MDA (r = -0.754, p = 0.002). Our results indicate a diminished amino acids metabolome in the serum of UPJO infants requiring surgery comparing to a conservative group.

Keywords: GC-MS; UPJO; amino acids; biomarkers; neonates; patient stratification; serum.