Frunza A. Improvement of the Methods to Prognosticate and Diagnose renal dysfunction of Preterm newborns with perinatal pathology.

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0824U002414

Applicant for

Specialization

  • 228 - Педіатрія

19-06-2024

Specialized Academic Board

ДФ 76.600.080

Bukovinian State Medical University

Essay

It has been established that renal dysfunction in preterm infants with perinatal pathology, in addition to non-specific clinical signs, is characterised by certain changes in laboratory markers and indicators of additional functional research methods. Biomarkers of dysfunction are: increased levels of cystatin C and creatinine in blood serum. Markers of tubulo-glomerular dysfunction are: increased urinary levels of microalbumin, alpha-1-microglobulin, beta-2-microglobulin, creatinine and urea. Taking into account the sensitivity and specificity of the tests, the most significant diagnostic tests for determining the severity of disorders of the functional state of the urinary system in premature infants, taking into account the gestational age and severity of perinatal pathology, were determined. An additional paraclinical criterion to characterise the severity of renal haemodynamic disturbances in preterm infants with perinatal pathology is the calculation of the RI index over the main renal arteries by Doppler examination. It has been established that an RI value of 0.70 or less indicates the absence of local haemodynamic disturbances, RI value of more than 0.71 indicates a moderate degree of renal haemodynamic disturbances, and an RI value of more than 0.85 indicates severe renal blood flow disturbances. The scientific provisions on the main pathogenetic mechanisms of urinary system dysfunction in preterm infants with perinatal pathology of varying severity have been expanded, in particular by defining the role of oxidative stress at birth. It was established that the main pathogenetic mechanisms of urinary system dysfunction in perinatal pathology in premature infants are tubulo-glomerular hypoxia accompanied by endothelial dysfunction, dysregulation of glomerular vasculogenesis mechanisms, development of microvascular leakage syndrome and activation of the inflammatory process accompanied by significant activation of free radical oxidation processes against the background of birth oxidative stress with insufficient antioxidant defence system. On the basis of the data obtained, taking into account the most sensitive and specific laboratory indicators of blood serum and urine, on the basis of multifactorial correlation analysis, a diagnostic model was developed to determine the urinary system dysfunction in premature infants with a probability of 83.87%, which has the following formula Yst = 0.29.f1 + 0.33.f2 + 0.07.f3 + 0.07.f4 + 0.05.f5 In order to make a diagnosis and determine the severity of renal dysfunction in perinatal pathology, an individual mathematical model should be developed for each child, taking into account the correlation coefficients of the factors and their significance in a given clinical case. The presence of renal dysfunction is confirmed taking into account the direction of the value vector, which is in the range "-1<Yst<+1": the value "Yst>+1" corresponds to significant disorders of the urinary system, the value "Yst<-1" corresponds to the absence of signs of urinary system dysfunction. The application of the proposed improved diagnostic complex, taking into account the analysis of anamnestic data, clinical features of the course of the disease, as well as the use of generally accepted and recommended additional methods of examination (cystatin C level in blood serum; microalbumin, alpha-1-microglobulin, beta-2-microglobulin levels in urine; calculation of RI on the basis of ultrasound examination data) allows to improve methods of prognostication, diagnosis and differential diagnosis of the severity of renal dysfunction in premature infants in the early neonatal period, to identify in time newborn risk groups for development of disorders of the functional state of the urinary system in conditions of perinatal pathology. The introduction of the recommended diagnostic complex, together with other measures to improve medical care, has improved the effectiveness of medical care for preterm infants and reduced the rate of early neonatal mortality in the neonatal intensive care unit of the Clinical Maternity Hospital No. 2 in Chernivtsi from 4.05‰ to 1.22‰ in 2019-2023.

Research papers

Babintseva A., Agafonova L., Koshurba I., Frunza A., Bevcyk A. Neonatal acute kidney injury: predictive and diagnostic value of urinary protein biomarkers. Buletin de Perinatologie. 2017;4:45-50.

Фрунза АВ. Гостре пошкодження нирок у передчасно народжених дітей: перинатальні чинники ризику. Неонатологія, хірургія та перинатальна медицина. 2019;9(2):45-52.

Phrunza A, Hodovanets Y, Babintseva A, Kovtyuk N, Makarova O. Laboratory Diagnostic Criteria of Renal Impairment in Premature Newborns with Severe Perinatal Pathology. Proceeding of CBU in Medicine and Pharmacy. 2020;1:12-7.

Годованець ЮД, Фрунза АВ. Перспективні уринарні біомаркери з огляду на патогенетичні механізми гострого пошкодження нирок у передчасно народжених дітей. Неонатологія, хірургія та перинатальна медицина. 2021;11(3):27-33.

Hodovanets, Y., & Frunza, A. Predictive factors and clinical features of urinary tract dysfunction in preterm infants.Neonatology, Surgery and Perinatal Medicine, 2023; 13(4): 40–48.

Frunza A., Hodovanets Yu. Renal dysfunction in preterm infants with perinatal pathology: risk factors, sensitivity and specificity of laboratory markers of damage. Neonatology, Surgery and Perinatal Medicine, 2024; 1(4): 30–40.

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