PATHOGENIC ASPECTS OF FUNCTIONAL DISORDERS OF THE URINARY SYSTEM IN TERM NEONATES WITH PATHOLOGY OF EARLY NEONATAL PERIOD

Abstract

Introduction. Formation of the majority of disease conditions in childhood and adulthood is associated with prolongation of pathological processes occurring in the periods of antenatal development and neonatal period. The main damaging factor in the development of disadaptation syndrome in neonates is hypoxia. Increase of knowledge concerning pathogenic links of post-hypoxic damage of the kidneys in the context of the body integrity is rather topical. Objective: to determine pathogenic links promoting formation of functional disorders of the urinary system condition in term neonates with pathology of early neonatal period. Materials and methods. Clinical-paraclinical examination of 80 term neonates has been carried out. The infants divided into four groups depending on the severity degree of disorders of the somatic and neurologic status and renal dysfunction. We used factor analysis of correlation dependences between the main markers of renal dysfunction was applied using the method of principal components in case of a turn of the primary varimax row by means of Statistica Program. Laboratory methods of examination included detection of the levels of creatinine, urea, potassium, sodium in the blood serum and urine; the level of cystatin C in the blood serum with calculation of glomerular filtration rate by creatinine and cystatin C; neutrophil gelatinase-associated lipocalin, total protein, albumin, immunoglobulin G, α1-microglobulin, β2- microglobulin in urine. Examination of infants included also detection of indices of the pro-oxidant system (intensity of oxidative modification of proteins in the blood, malonic dialdehyde in erythrocytes and urine), and antioxidant defense system (ceruloplasmin, HS-groups in plasma, catalase, glucose-S-transferase and γ-glutamyl trasnferase in plasma, glutathione reductase and glucose-6-phosphate dehydrogenase in erythrocytes. Activity of enzymes in urine was investigated and their ratio to the level of creatinine in urine (cholinesterase, aspartate aminopeptidase, alanine aminopeptidase, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transpeptidase. Results and discussion. By means of Kettel method with detection of «Screen plot» criterion it determined six major factors which are important in understanding the character of correlation dependences between the indices involving 63.3% of general dispersion. Complex interrelated mechanisms of equilibrium disorders between stress-induced and stress-limited systems were found to be in the basis of formation of renal dysfunction in term neonates with disadaptation syndrome. At the same time, under conditions of moderate oxygen starvation activation of defense mechanisms of the body is detected, their action is directed to stabilization of hemodynamic and neuro-endocrine mechanisms, activation of metabolic processes promoting maintenance of the stability of the major vital functions including those of the urinary system. Severe hypoxia is associated with deep metabolic disorders with exhaustion of energy and plastic cellular pool and development of pathologic oxidative stress resulting in to destruction of anatomical integrity of the glomerular and tubular renal apparatus, damage of the cellular structures of the kidney epithelium. Considering the conception of the body «integrity» considerable disorders of the functional state of the main excretory organ are associated with further development of endogenous intoxication syndrome and accumulation of final metabolic products, which intensifies the consequences of porthypoxia lesion with the formation of syndrome of multiple organ failure. Conclusions. Conditions of oxygen starvation together with initiation of reaction of pathologic delivery oxidative stress result in deep disorders of interrelations between pro-oxidant and anti-oxidant components, imbalance of ionic homeostasis, changes of metabolic equilibrium with disorders of energy and plastic supply of the cellular functions, further initiation of the processes of apoptosis and/or necrosis. These stipulate organic changes of the renal structural elements and loss of their functional activity with disorders of the mechanisms of glomerular filtration, tubular reabsorption and secretion against the ground of pathological changes of the renal hemodynamics and imbalance of hormonal homeostasis. Understanding of the main pathogenic links of renal dysfunction formation in neonates of the first week of their life can enable to improve the ways of therapeutic correction directed to the elimination of pathological signs and prevention of complications in future.