RENAL DYSFUNCTION IN PRETERM INFANTS WITH PERINATAL PATHOLOGY: RISK FACTORS, SENSITIVITY AND SPECIFICITY OF LABORATORY MARKERS OF DAMAGE

Abstract

The main burden of neonatal morbidity in critically ill preterm infants, despite signifi cant achievements and rapid development of care technologies, is most often associated with neonatal sepsis, perinatal asphyxia and the development of multiple organ failure syndrome. As a component of this syndrome, newborns with combined perinatal pathology in the early neonatal period manifest severe renal dysfunction up to acute kidney injury, which is closely correlated with increased mortality. The incidence of acute kidney injury in critically ill preterm infants varies widely, ranging from 25 to 77 % according to diff erent neonatal data. A major problem in the fi eld of neonatal nephrology is the lack of uniform approaches for the diagnosis of moderate and severe renal dysfunction at the subclinical stage, which would allow the timely formation of risk groups and the optimization of interventional strategies. Aim of the study. To analyze the data on clinical characteristics, risk factors, and results of additional paraclinical examinations in preterm infants with gestational age of 34-36/6 weeks who had severe and moderate perinatal pathology during the early neonatal period. Material and methods. A comprehensive study of 91 premature infants with moderate and severe perinatal pathology was conducted, of which group I consisted of 30 children with severe perinatal pathology at 34-36/6 weeks’ gestation, group II – 30 children with moderate perinatal pathology at 34-36/6 weeks’ gestation; group III (control) consisted of 31 conditionally healthy premature infants at 34-36/6 weeks’ gestation. The diagnosis of acute kidney injury in neonates in the comparison groups was made according to the International Criteria for Kidney Disease: Improving Global Outcomes as modifi ed by J. G. Jetton and D. J. Askenazi (2015). The international scale Neonatal Multiple Organ Dysfunction Score was used to assess the severity of multiorgan dysfunction in perinatal pathology. The eff ectiveness of therapeutic interventions was assessed using the international scale Neonatal Therapeutic Intervention Scoring Scale, and the severity of the patient’s condition in dynamics was assessed using the neonatal scale Score for Neonatal Acute Physiology. Methods of laboratory research. The study of the biochemical spectrum of urine in children of the observation groups, in particular, the determination of the level of markers of kidney damage – alpha-1-microglobulin, beta-2-microglobulin, microalbumin, cystatin C was carried out on the basis of the problematic research laboratory of the Bukovinian State Medical University of the Ministry of Health of Ukraine using the automatic analyzer «ACCENT-200» and «ACCENT-200 II CEN». Urine was collected on the 3rd day of life (between 48-72 hours of life), in sterile disposable containers, in the amount of at least 5 ml. At the same time, a blood sample for cystatin C determination was taken in the amount of 0.5-1.0 ml, in accordance with the rules of asepsis and antisepsis in disposable sterile tubes. A turbodimensional immunoassay was used to determine the concentration of cystatin C and urinary microalbumin. Determination of alpha-1-microglobulin was performed using an ACCENT-200 automated analyzer by measuring agglutination by change in absorbance (572 nm), with actual concentration determined by interpolation from a calibration curve constructed using calibrators of known concentration. The concentration of beta-2-microglobulin in urine was determined by the method of competitive chemiluminescence analysis. The studies were conducted in accordance with the basic provisions of GCP (1996), the Convention of the Council of Europe on Human Rights and Biomedicine (April 4, 1997), the World Medical Association Declaration of Helsinki on Ethical Principles for Research Involving Human Subjects (1964-2008), Order of the Ministry of Health of Ukraine No. 690 of September 23, 2009 (as amended by Order of the Ministry of Health of Ukraine No. 523 of July 12, 2012). Statistical analysis of the results was performed using Statistica 10 software (StatSoft Inc., USA, 2010), MedCalc software (version 16.1) with calculation of chi-squared, odds ratio (OR), 95 % confi dence interval (CI), statistically signifi cant diff erences between the study groups were considered at a value of p<0.005. Receiver operating characteristic (ROC) curves, area under ROC (AUROC), sensitivity (SN), and specifi city (SP) were analyzed using MedCalc software (version 16.1). The research work was carried out within the framework of research of the Department of Pediatrics, Neonatology and Perinatal Medicine of the Bukovinian State Medical University: Research project «Improvement of directions of prognostication, diagnosis and treatment of perinatal pathology in newborns and infants, optimization of schemes of catamnestic observation and rehabilitation» (State registration number 0115U002768, term of implementation 2015-2019); Research project «Chronobiological and adaptive aspects and features of vegetative regulation in pathological conditions in children of diff erent age groups» (State registration number 0122U002245, term of implementation 2020-2024). Study results. The data obtained showed statistically signifi cant associations between the risk of severe renal dysfunction and a number of antenatal and postnatal factors that adversely aff ect the course of the early neonatal period. These included fetal distress during pregnancy and delivery, emergency cesarean section, risk of spontaneous abortion and preterm birth, and impaired fetal- placental blood fl ow. Statistically signifi cant associations with the development of moderate and severe renal dysfunction are associated with a burdened history of maternal extragenital pathology, namely cardiovascular, urinary system, and anemia (p<0.005). The structure of perinatal pathology in preterm infants is often combined and diffi cult to diagnose. A signifi cant proportion of newborns had clinical manifestations of multiple organ failure syndrome, including signs of renal dysfunction. Therefore, it is expedient to study a set of the latest potential biomarkers of renal dysfunction, such as cystatin C, alpha-1-microglobulin, beta-2-microglobulin and microalbumin, in order to create an appropriate prognostic model and timely form risk groups among this category of children. Conclusions. The basis for the development of moderate and severe renal dysfunction in premature infants with perinatal pathology is polyetiology against the background of morphological and functional immaturity of the body, which has a clear relationship with gestational age and birth weight. The compensatory and adaptive properties of the «immature» kidneys at birth are limited, which, in the presence of combined pathology, plays a signifi cant role in shaping the severity of the course of the disease. Early prognosis and diagnosis of renal dysfunction in the early stages of its development makes it possible to improve the quality and eff ectiveness of medical care and improve treatment outcomes.

Keywords

• Children; Preterm Infants; Acute Kidney Injury; Risk Factors; Clinical Characteristics; Laboratory Diagnostics