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

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

doi:10.3390/jcm10071467

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.

Highlights

One of the most common abnormalities detected upon prenatal ultrasound examination is hydronephrosis [1]
Serum samples of 42 neonates and infants with ureteropelvic junction obstruction (UPJO) and 19 age-matched healthy controls were analyzed by gas chromatography–mass spectrometry (GC–MS) for the quantitative determination of several amino acids and their metabolites, especially including the L-arginine/nitric oxide (NO) pathway, which has been reported to play a role in UPJO [19,20,21]
The results of the present study observed by GC–MS and those of a previous study observed by Hydrophilic interaction liquid chromatography (HILIC)–MS/MS, i.e., by using two orthogonal analytical techniques on serum samples, revealed in part confirmative and in part complementary observations and potential biomarkers that are considered to help better understand the underlying biochemical mechanisms and to lead to an improvement of the clinical situation of UPJO infants by surgical and potentially by therapeutic treatment

Summary

Introduction

One of the most common abnormalities detected upon prenatal ultrasound examination is hydronephrosis [1]. The management of a patient who suffers from mild or severe hydronephrosis is considered “easier” since the clinical outcome is usually predictable. Children suffering from severe hydronephrosis will require surgical intervention in almost 100% of the cases [5]. Patients suffering from moderate hydronephrosis present with a significant variability of clinical outcomes. Given the wide variation in the clinical course of children with moderate hydronephrosis, there is no unanimity on the criteria for surgical treatment [6]. Detection of hydronephrosis has reduced cases of severe renal damage due to obstruction or infections. The challenge remains the following: How to predict at an early stage which of these prenatally detected infants will benefit from surgical treatment before irreversible renal damage is established

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