Omics technologies in screening for kidney disease in children with congenital uropathy

Abstract

Background: Primary vesicoureteral reflux (VUR) is the most common congenital uropathy (CU) in children, leading to the development of reflux nephropathy and chronic kidney disease, reaching the terminal stage in 25-60% of patients. The insufficient sensitivity of modern methods of instrumental and laboratory diagnostics of the initial stages of renal parenchyma damage dictates the need to develop new non-invasive technologies for screening and monitoring kidney conditions in patients with CU.
 Aims: To evaluate the possibility of separating groups of healthy children and children with kidney damage with CU using the analysis of the mass spectra of volatile organic compounds (VOCs) in urine samples.
 Materials and methods: This study involved 42 patients (average age 5.4 + 2.3 years), divided into 2 groups: group 1 24 children with congenital uropathies (grade II-V PMR) and comparison group 2 - 18 patients with minor surgical pathology without pathology of the urinary system. Urine samples were collected before the start of treatment. Composition analysis of VOCs samples was carried out through express-analysis method for biological objects at atmospheric pressure without preliminary preparation using a mass spectrometer with ionization by laser plasma radiation. Urinary levels of markers of inflammation (MCP-1, IL-8, IL-18), angiogenesis (VEGF) and fibrosis (TGF-1) were measured by solid-phase ELISA.
 Results: Composition changes in urine VOCs were detected in group 1 patients with congenital uropathies (VUR). These changes made it possible to distinguish group 1 samples from the comparison group 2. Creatinine level and glomerular filtration rate (GFR) in both groups had no statistical difference. An increase in concentration of inflammatory markers MCP-1, IL-18, IL-8, VEGF angiogenesis and TGF-1 fibrosis was observed in the urine of children with congenital uropathies (VUR) (p0.001). In group 1 patients the concentration of markers did not correlate with the reflux level.
 Conclusions: The performed research allowed to find a set of peaks in the recorded mass spectra, according to which it is possible to divide groups into healthy and sick. It also demonstrated the potential of volatolom analysis to detect kidney damage in children with congenital uropathies. The use of standard methods: creatinine and GFR did not allow us to find a threshold value to divide patient into healthy and sick groups. The increase of biomarkers of inflammation, angiogenesis and fibrosis in the urine of children with congenital uropathies confirmed the presence of persistent kidney damage, parenchymal hypoxia, activation of fibrosis and inflammation in children with CU kidneys.