Acute kidney injury in neonates: risk factors, pathogenesis bases, principles of diagnostics and medical management.

Babintseva А.G., Hodovanets Yu.D. Acute kidney injury in neonates: risk factors, pathogenesis bases, principles of diagnostics and medical management. – Chernivtsi: BSMU, 2019. – 200 p.

The monograph presents generalization of the modern literature data and the results of own original studies concerning etiopathogenic mechanisms and clinical-paraclinical peculiarities of renal dysfunction in neonates with perinatal pathology. The algorithm of prognostication and diagnostics of acute renal injury is reported using up-to-date laboratory and functional markers.

Maternal age over 35, chronic urinary pathology, gestational maternal pyelonephritis, life threatening fetal distress during pregnancy and/or labor, have been found to be the most valuable risk factors promoting development of acute kidney injury in critically sick neonates. Statistically valuable associations have been determined between the formation of acute kidney injury in neonates with assessment by Apgar score less than 3 points at the end of the first and fifth minute after birth, diagnosis of severe asphyxia, arterial hypotension syndrome, “white spot” positive symptom and gastro-intestinal disorders. Additional postnatal risk factors deteriorating renal dysfunction in neonates are administration of loop diuretics, drugs of inotropic and sedative action. 

The main clinical-paraclinical symptoms indicative of severe disorders of the urinary system functional state in neonates with perinatal pathology have been determined those including swelling syndrome, pathologic positive balance of the body weight ≥ 5% from the initial one, and pathologic hourly urine output ≤ 2 ml/kg/hour during first 72 hours of life. 

Increased severity of renal dysfunction in early neonatal period is associated with pathologic changes of glomerular barrier which is evidenced by an increased level of cystatin C in the blood serum, increased urinary excretion of the whole protein, albumin and immunoglobulin G, and tubular dysfunction evidenced by excessive urinary excretion of neutrophil gelatinase-associated lipocalin, α₁-microglobulin and β₂-microglobulin.

Formation of renal dysfunction in neonates is associated with statistically valuable activity of glomerular filtration marker – cholinesterase – in urine, as well as superficial enzymes of «brush border» (alkaline phosphatase, γ-glutamyltransferase), cytosol (alanine aminotransferase) and mitochondria (aspartate aminotransferase) of the nephrothelial cells.

The data of instrumental examination have evidenced prevailing pathologic mechanisms activating vasoconstriction of the renal vessels with inhibition of rate characteristics of the renal blood circulation and deterioration of general renal vascularization in neonates during their first week of life under conditions of severe perinatal pathology. 

Increasing severity of perinatal pathology and thereafter renal dysfunction in neonates is associated with reliable intensity increase of protein oxidative modification in the blood plasma and Malone aldehyde in the erythrocytes and urine, as well as decreased enzymatic activity of glutathione reductase in erythrocytes, glutathione-S-transferase and γ-glutamyl transferase in the blood plasma, and the level of ceruloplasmin in the blood plasma. 

The scientific knowledge concerning pathogenic mechanisms of renal dysfunction formation in neonates has been extended, namely, the role of pathologic delivery oxidative stress reactions against the ground of reduced activity of the antioxidant protective system, ionic homeostasis imbalance, disorders of metabolism and regional renal hemodynamics resulting in disorders of glomerular filtration, tubular reabsorption and secretion.

The algorithm of prognosis, diagnostics and differentiation diagnostics has been suggested to determine severity of renal dysfunction in neonates with pathology of early neonatal period by means of discriminating analysis of the most valuable indexed perinatal risk factors and a complex of additional paraclinical indices.

The system of diagnostic-therapeutic measures directed to prevention and correction of renal dysfunction in patients of intensive neonatal resuscitation units has been elaborated.  In addition to the common methods used in the complex of treatment the agent with anti-hypoxic and antioxidant action has been introduced containing succinic acid, nicotinamide, riboxin and riboflavin in a comprehensive treatment of children with the signs of moderate and severe perinatal pathology; as well as a drug from methyl xanthine group with theophylline as an active agent to prevent adenosine-induced renal vasoconstriction and development of acute kidney injury in critically sick neonates.

The monograph is of a certain scientific-practical value, it is recommended for scientists, neonatologists, pediatricians, pediatric nephrologists, pediatric anaesthesiologists, interns, and medical students.   

Key words: Neonate; Kidney; Renal Dysfunction; Acute Kidney Injury; Renal Marker; Oxidative Stress; Antioxidants; Methylxanthine.