STATISTICAL DATA AND ANALYSIS OF LITERATURE SOURCES ON PATHOPHYSIOLOGICAL MECHANISMS OF THE CROSSTALK BETWEEN ACUTE KIDNEY AND LIVER INJURY IN PRETERM NEWBORNS DURING THE EARLY NEONATAL PERIOD

Acute kidney injury (AKI) and acute liver failure (ALF) are common and potentially dangerous complications in neonates admitted to the NICU. This article reviews data on the adverse effects of AKI on liver function and the development of ALF in preterm neonates. Infants with hemodynamically significant patent ductus arteriosus (hsPDA) are highlighted. Aim. To analyze risk factors and the incidence of liver damage in preterm newborns who experienced AKI during the early neonatal period. Materials and methods. The study retrospectively analyzed the medical history of 74 preterm infants admitted to the anesthesiology and neonatal intensive care unit. Patients were examined using a complex of general clinical, biochemical, immunoenzymatic, and instrumental methods, as well as measuring the urinary neutrophil gelatinase-associated lipocalin (NGAL) biomarker and performing statistical analysis. Scientific research was conducted in accordance with the provisions of GCP (1996), the Convention of the Council of Europe on Human Rights and Biomedicine (April 4, 1997), the Declaration of Helsinki of the World Medical Association on the Ethical Principles for Conducting Scientific Research with Human Participation (1964-2008), and the Order of the Ministry of Health of Ukraine No. 690 dated September 23, 2009 (as amended by the Order of the Ministry of Health of Ukraine No. 523 dated July 12, 2012). The distribution of patients was carried out depending on the AKI development, that was diagnosed and stratified by the severity based on the neonatal modification of the 2012 KDIGO criteria. AKI was diagnosed according to the Pediatric Acute Liver Failure Study Group recommendations: prothrombin time ≥20 seconds after vitamin K administration or International Normalized Ratio values ≥2 units). Results. AKI was diagnosed in 36.5% of all preterm infants studied and 77.8% of them had hsPDA. ALF manifestations were mostly detected on day 5 and accounted for 79.3% of infants with AKI, 3 times more frequent in its severe course (p<0.05) and 4.2 times more frequent than in those without AKI signs (p<0.05). Correlation analysis of blood creatinine levels on days 3 and 10 showed a direct association with the development of AKI (ρ=0.496, p˂0.05 and ρ=0.456, p˂0.05, respectively). At the same time, AKI was 3.4 times (p<0.05) more severe when combined with ALF. An increase in bilirubin levels to levels indicating the need for phototherapy was directly correlated with the development of AKI (ρ=0.544, p˂0.05). Episodes of hypoglycemia and the need for its additional correction were directly correlated with the severity and duration of AKI (ρ=0.349, p˂0.05 and ρ=0.556, p˂0.05, respectively). In addition, 78% of the children were predisposed to lactic acidosis. The diagnostic value of urinary NGAL for AKI in preterm infants was 229.7±94.82 (208.5; 176-297.3). An NGAL concentration of 249.0±113.27 (210; 185.5-302) tripled the odds of developing AKI (p˂0.05). Elevated urine NGAL was an independent prognostic factor for 28-day mortality. Unfortunately, all 6 infants with urine NGAL levels above 250 μg/L developed severe AKI with ALF manifestations and died in the neonatal period. Analysis of the perinatal history of the studied preterm infants showed a statistically significant association between AKI and ALF in those infants whose mothers had a history of renal disease, chronic infection, or chorioamnionitis. Conclusions. Understanding the impact of acute kidney injury on liver function in preterm infants can help address the issues of early diagnosis, management and prevention of acute liver failure and improve outcomes of care for these infants. Identification of early pathological manifestations using biomarkers and analysis of patient history are needed to prevent complications caused by the complex and potentially dangerous vicious circle related to kidney-liver crosstalk.