Neonatal acute kidney injury: predictive and diagnostic value of urinary protein biomarkers

Department of Pediatrics, Neonatology and Perinatal Medicine, Higher State Educational Establishment of Ukraine“Bukovinian State Medical University”, Chernivtsi, UkraineBackground. The prevalence of acute kidney injury (AKI) reaches ~30% in neonates admitted to a tertiary level neonatal intensive care unit. Novel urinary biomarkers are useful for the prediction and diagnosis of AKI. The objective of this work was to determine the predictive and diagnostic value of urinary protein biomarkers for AKI in critically sick full-term newborns. Materials and methods. A prospective cohort study of 150 full-term neonates was performed. Group I included 55 healthy newborns, group II – 50 critically ill newborns without AKI, group III – 45 critically ill newborns with AKI. Creatinine levels in serum (SCr), urinary concentration of total protein (UTPr), urinary albumin (UAlb), urinary immunoglobulin G (UIgG), urinary α1-microglobulin (Uα1-MG) and β2-microglobulin (Uβ2-MG) were measured on the 3rd day of life. In case the data were available, 2×2 tables were constructed to derive sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and cut-off level of urinary protein biomarkers. The area under the receiver operating characteristic (AUROC) curve was used to deduce the diagnostic accuracies of them. Results. Considering AUROC values, the results of the conducted statistical analysis demonstrated that the biggest diagnostic value concerning AKI determination in critically ill term newborns was peculiar for the model with determination of UIgG level (AUROC 0.79; 95% СІ 0.69-0.88, р<0.001 with сut-off level ≥ 5.1 mg/L). Similar diagnostic value was found in the models with determination of Uα1-MG (AUROC 0.73; 95% СІ 0.64-0.84, р<0.05 with сut-off level ≥ 42 mg/L) and UTPr (AUROC 0.73; 95% СІ 0.62-0.83, р<0.05 with сut-off level ≥ 186 mg/L). The model with determination of UAlb (AUROC 0.64; 95% СІ 0.53-0.76, р<0.05 with сut-off level ≥ 23.0 mg/L) possessed the least diagnostic value. The laboratory test with determination of Uβ2-MG level demonstrated the absence of diagnostic value concerning AKI determination in term newborns (AUROC 0.56; 95% СІ 0.5-0.68, р>0.05 with сut-off level ≥ 2.95 mg/L). Conclusions: 1. A comprehensive clinical-paraclinical examination should be performed for timely diagnostics of AKI in critically ill term newborns with determination of early markers of renal dysfunction including urinary protein biomarkers. 2. Considering the values of AUROC the level of diagnostic value of the presented biomarkers concerning detection of AKI was determined: UIgG > Uα1-MG, UTPr > UAlb with absent diagnostic value of Uβ2-MG. 3. None of the presented diagnostic models demonstrated high discriminating ability with high values of Se and Sp at the same time concerning detection of AKI in critically ill newborns

Statutul sistemelor pro-oxidant şi antioxidant de protecţie la nou-născuţii critic bolnavi: un studiu preliminar

Department of Pediatrics, Neonatology and Perinatal Medicine of Bukovinian State Medical University, UkraineBackground & objectives: the objective of this research is to study the status of the pro-oxidant and antioxidant defense systems and the relations between different components of these systems in critically ill newborns. Methods: the basic group of observation included 25 ill-term neonates who had clinical symptoms of disorders on their first week of life and received treatment in the Neonatal Intensive Care Unit. The control group included 37 apparently healthy term neonates. The study included detection of the pro-oxidant system (oxidative modification of proteins (OMP), malondialdehyde (MDA)) and antioxidant defense system (ceruloplasmin (CP), catalase (CT), gamma-glutamyl transpeptidase (GGTP)) at 48-72 hours of life. Results: The obtained results showed that newborns from the basic group as compared to the children from the control group had significantly increased OMP and MDA levels and CP activity and significantly increased CT and GGTP activities. The formation of qualitatively new relations between components of pro-oxidant and antioxidant systems and individual components in the middle of the antioxidant system in ill newborns was found in this study. Interpretation & conclusions: we concluded that term newborns who had clinical symptoms of disorders on their first week of life demonstrated excessive activation of pro-oxidant processes, inadequate antioxidant protection, and formation of new relations between components of these systems and individual components in the middle of the antioxidant system. The immature all systems and organs of these babies along with both intracellular oxygen-free radical toxicity and extracellularly generated cytotoxic products of activated inflammatory cells need special medical protection as a part of postnatal therapeutic care.Context şi Obiective: obiectivul acestei cercetări este de a studia statutul sistemelor pro-oxidant şi antioxidant de protecţie şi relaţiile dintre diferitele componente ale acestor sisteme la nou-născuţii critic bolnavi. Metode: grupul de studiu a inclus 25 copii bolnavi născuţi la termen, care au avut semne clinice patologice în prima lor săptămână de viaţă şi care au primit tratament în secţia de terapie intensivă pentru nou-născuţi. Grupul de control a inclus 37 copii născuţi la termen şi aparent sănătoşi. Studiul a inclus detecţia sistemului pro-oxidant (modifi - carea oxidativă a proteinelor (MOP), malondialdehida (MDA)) şi sistemului antioxidant de protecţie (ceruloplasmina (CP), catalaza (CT), gama-glutamil transpeptidaza (GGT)) la 48-72 ore de viaţă. Rezultate: rezultatele obţinute au arătat că la nou-născuţii din grupul de studiu, comparativ cu copiii din grupul de control, a crescut în mod semnificativ nivelul MOP şi MDA şi activitatea CP, precum şi semnificativ a crescut CT şi activitatea GGTP. Am stabilit formarea relaţiilor calitativ noi între componentele sistemelor pro-oxidant şi antioxidant şi componentele individuale din interiorul sistemului antioxidant la nou-născuţii bolnavi. Interpretare şi concluzii: am concluzionat că copiii născuţi la termen, care au avut semne clinice patologice în prima lor săptămână de viaţă au demonstrat o activare excesivă a proceselor pro-oxidante, o protecţie antioxidantă inadecvată şi formarea relaţiilor noi între componentele acestor sisteme şi componente individuale în interiorul sistemului antioxidant. Imaturitatea sistemelor şi organelor la aceşti copii, toxicitatea oxigenului intracelular al radicalilor liberi şi produsele citotoxice generate extracelular de celulele infl amatorii activate necesită o protecţie medicală specială ca parte a îngrijirii terapeutice postnatale

Evaluating the effectiveness of integrated marketing communications while implementing a CRM system in the agricultural industry

This article deals with the problem of insufficient objective characteristics for determining the productivity of integrated marketing communications in business and organizations of various fields of activity, including those involved in ecology, energy, etc. The relevance of the work is due to the massive distribution of various marketing communications tools, often customized and used today through CRM systems. The aim of the study is to determine the criteria for evaluating the effectiveness of integrated marketing communications tools, reflected in CRM systems. The author uses methods of the structural and functional approach. The research is based on the descriptive and analytical method. The result of the work is a list of parameters reflected in the CRM system. They can help consider the degree of effectiveness of integrated marketing communications used in business and organizations of various fields of activity, including those involved in the field of ecology, energy, etc. Moreover, the list of criteria can be used to determine the degree of successful implementation of a CRM system and individual tools of integrated marketing communications

Urinary protein markers of renal dysfunction in full-term newborns with disorders of early neonatal period

Background: Urinary proteins may help to understand the physiology and diagnose renal dysfunction in sick infants. The renal function in ill full-term newborns with disorders of early neonatal period by means of detecting specific protein biomarkers in the urine was studied. Materials and methods: A prospective cohort study on 205 full-term newborns was performed including 55 healthy infants, 55 newborns with clinical signs of moderate disorders of early neonatal period, 50 newborns with severe neonatal disorders without acute kidney injury (AKI), and 45 newborns with both severe neonatal disorders and AKI. The urinary concentrations of total protein (UTPr), albumin (UAlb), immunoglobulin G (UIgG), α1-microglobulin (Uα1-MG), and β2-microglobulin (Uβ2-MG) were determined by means of laboratory tests. Results: As compared to healthy newborns, full-term neonates with moderate disorders of early neonatal period developed dysfunction of the glomerular membrane (selective proteinuria with excessive excretion of UAlb), and proximal tubules (increased Uα1-MG). More severe neonatal disorders in term newborns are accompanied by selective proteinuria together with more pronounced tubular failure (excessive urinary excretion of Uα1-MG and Uβ2-MG). Formation of AKI in term infants is associated with complex disorders of all structural elements of the nephron, manifested by extremely high levels of total protein markers of glomerular (UTPr, UAlb and UIgG) and tubular (Uα1-MG and Uβ2-MG) dysfunction in urine. Conclusions: The measurement of urinary protein biomarkers in sick full-term newborns with clinical signs of disorders of early neonatal period demonstrated renal dysfunction not only in infants with AKI. The biochemical changes found in critically ill newborns require timely diagnosis promoting the right choice of intensive therapy with the aim to prevent the development of severe renal pathology and chronic renal failure in the future