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

A. Frunză, Y. Hodovanets
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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 paraclinicalexaminations 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 wasconducted, 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 Criteriafor Kidney Disease: Improving Global Outcomes as modifi ed by J. G. Jetton and D. J. Askenazi (2015). The international scaleNeonatal 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 Europeon Human Rights and Biomedicine (April 4, 1997), the World Medical Association Declaration of Helsinki on Ethical Principlesfor 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 andPerinatal 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 dysfunctionand 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. \nConclusions. The basis for the development of moderate and severe renal dysfunction in premature infants with perinatalpathology is polyetiology against the background of morphological and functional immaturity of the body, which has a clearrelationship 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.","PeriodicalId":162458,"journal":{"name":"Neonatology, surgery and perinatal medicine","volume":"18 8","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neonatology, surgery and perinatal medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.24061/2413-4260.xiv.1.51.2024.5","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

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 paraclinicalexaminations 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 wasconducted, 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 Criteriafor Kidney Disease: Improving Global Outcomes as modifi ed by J. G. Jetton and D. J. Askenazi (2015). The international scaleNeonatal 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 Europeon Human Rights and Biomedicine (April 4, 1997), the World Medical Association Declaration of Helsinki on Ethical Principlesfor 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 andPerinatal 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 dysfunctionand 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 perinatalpathology is polyetiology against the background of morphological and functional immaturity of the body, which has a clearrelationship 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.
围产期病理早产儿的肾功能障碍:危险因素、实验室损伤标志物的敏感性和特异性
研究工作在布科维尼亚国立医科大学儿科、新生儿科和围产期医学系的研究框架内进行:研究项目 "改进新生儿和婴儿围产期病理学的预后、诊断和治疗方向,优化孕期观察和康复计划"(国家注册号 0115U002768,实施期限 2015-2019年);研究项目 "不同年龄组儿童病理情况下植物调节的时间生物学和适应方面及特点"(国家注册号 0122U002245,实施期限 2020-2024年)。研究结果表明,从统计学角度看,严重肾功能不全的风险与一些对新生儿早期发育产生不利影响的产前和产后因素有关。这些因素包括孕期和分娩时的胎儿窘迫、紧急剖宫产、自然流产和早产风险以及胎儿-胎盘血流受损。据统计,中度和重度肾功能不全的发生与孕产妇患有心血管、泌尿系统和贫血等先天性疾病有关(P<0.005)。早产儿围产期病理结构往往是综合的,难以诊断。相当一部分新生儿有多器官功能衰竭综合征的临床表现,包括肾功能不全的迹象。因此,研究一组最新的肾功能障碍潜在生物标志物(如胱抑素 C、α-1-微球蛋白、β-2-微球蛋白和微量白蛋白),以建立一个适当的预后模型,并及时在这类儿童中形成风险群体,是非常适宜的。结论患有围产期疾病的早产儿出现中度和重度肾功能不全的基础是机体形态和功能不成熟背景下的多病因,这与胎龄和出生体重有明显的关系。出生时 "未成熟 "肾脏的代偿和适应能力有限,在合并病理的情况下,这对病程的严重程度起着重要作用。在肾功能不全的早期阶段对其进行早期预后和诊断,可以提高医疗护理的质量和效率,改善治疗效果。
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