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

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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-β1) 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-β1 fibrosis was observed in the urine of children with congenital uropathies (VUR) (p<0.001). 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.

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About the authors

Aygul B. Bukharina

Prokhorov General Physics Institute of the Russian Academy of Sciences

Email: ay15@mail.ru
ORCID iD: 0000-0003-3627-3302
SPIN-code: 3189-1112
Russian Federation, Moscow

Anastasia O. Fedulkina

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: n.fedulkina@mail.ru
ORCID iD: 0000-0002-6232-2123

Student

Russian Federation, Moscow

Karmina N. Demidova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: negmatova.karmina@mail.ru
ORCID iD: 0000-0002-4638-6370
SPIN-code: 9281-4273
Russian Federation, Moscow

Andrei V. Pento

Prokhorov General Physics Institute of the Russian Academy of Sciences

Email: pentan@mail.ru
ORCID iD: 0000-0001-5122-8265
SPIN-code: 6035-3748

PhD in Physical and Mathematical Sciences

Russian Federation, Moscow

Larisa D. Maltseva

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: lamapost@mail.ru
ORCID iD: 0000-0002-4380-4522
SPIN-code: 7725-2499

PhD, Assistant Professor

Russian Federation, Moscow

Yaroslav O. Simanovsky

Prokhorov General Physics Institute of the Russian Academy of Sciences

Email: yaroslav@kapella.gpi.ru
ORCID iD: 0000-0003-0779-1135
SPIN-code: 3438-9329

PhD in Technical Sciences

Russian Federation, Moscow

Sergei M. Nikiforov

Prokhorov General Physics Institute of the Russian Academy of Sciences

Email: 15925@mail.ru
ORCID iD: 0000-0001-7510-4355
SPIN-code: 9359-0557

PhD in Physical and Mathematical Sciences

Russian Federation, Moscow

Olga L. Morozova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: morozova_ol@list.ru
ORCID iD: 0000-0003-2453-1319
SPIN-code: 1567-4113
Scopus Author ID: 55805379800
ResearcherId: R-9125-2017

MD, PhD, Professor

Russian Federation, Moscow

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Supplementary files

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1. Figure 1. Scheme of a mass spectrometer with a VOC input device: 1 - reflectron time-of-flight mass spectrometer; 2 - laser plasma created by pulsed laser radiation; 3 - metal target; 4 - pulsed Nd:YAG laser; 5 - lens with a focal length of 5 cm; 6 - ionization chamber; 7 - a test tube with a urine sample installed on the pneumatic connector

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2. Figure 2. Dependence of the total ion current on time in the study of urine samples: 1 — area of air displacement in the test tube by argon, duration ~ 30 s (shaded in blue); 2 — recording section of a stable mass spectrum, duration ~ 120 s (shaded red) and when an empty tube is installed (unshaded area). The inset shows a single mass spectrum of a urine sample.

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3. Figure 3. The result of applying the principal component method to the analysis of mass spectra of VOCs in the urine of patients (blue dots) and healthy (red dots)

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4. Figure 4. Comparison of the results of the mass spectrometric analysis of VOC and the test for creatinine and GFR: A - comparison with the test for creatinine; B - comparison with GFR test

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