SERUM CYSTATIN C, URINARY α1-MICROGLOBULIN AND β2-MICROGLOBULIN AS MARKERS TO DETECT NEONATAL ACUTE KIDNEY INJURY

The risk of acute kidney injury (AKI) in hospitalized critically ill newborns without primary renal disease remains to be high in both term and premature infants. The diagnosis of AKI in newborns is problematic with current methods that rely on two functional abnormalities: functional changes in serum creatinine (SCr) and urine output. They both are late consequences of injury and not predictive markers of the injury itself [1]. Novel urinary biomarkers are useful for the prediction of AKI. Most promising are the urine markers neutrophil gelatinase-associated lipocalin, interleukin-18, kidney injury molecule and other. Each of these has shown considerable promise diagnosing AKI earlier than SCr using disease controls [2, 3]. This clinical study investigated whether two markers of glomerular dysfunction (serum creatinine (SCr) and serum cystatin C (SCysC)) and two markers of tubular dysfunction (urinary α1-microglobulin (Uα1-MG) and urinary β2-microglobulin (Uβ2-MG)) were suitable for detecting AKI according to the neonatal Acute Kidney Injury (nAKIN) criteria. Materials and Methods. A prospective cohort study of 95 critically ill full-term neonates was performed. Fifty critically ill newborns without AKI (group I) and forty five critically ill newborns with AKI (group II) were included. The definition of AKI proposed by Jetton and Askenazi based on the nAKIN classification was used: increase of SCr by 0.3 mg/dl (25.6 μmol/l) or by 150-200% from the previous value and/or level of urine output less than 0.5 ml/kg/h for 6 to 12 hours [4]. The exclusion criteria of the study were birth weight ≤ 2500g, early neonatal sepsis and major congenital anomalies of the kidneys and urinary tract. Urine and blood samples were collected on the 2-3rd day and in cases of anuria/oliguria after restoration of diuresis. SCr level was measured using enzymatic method by ADVIA®KC 1800/2400 Chemistry System (Siemens Healthcare Diagnostics, USA), SCysC, Uα1-MG and Uβ2-MG levels were measured using immunonephelometric method by BN ProSpec Siemens (Siemens Healthcare Diagnostics, USA). All the tests kits were manufactured by the laboratory Gemeinschaftslabor Cottbus (Germany). The data obtained were statistically processed by means of the programs Statistica 7.0 (StatSoftInc., USA) and MedCalc Software (Version 16.1). The results of each group are expressed as mean (M) and standard error (m) for symmetric distribution. The normality of data distribution was tested using Shapiro-Wilks test for sample size ≥ 30. To compare continuous variables parametric tests (independent t test) were used. Fisher’s exact test was used to compare categorical variables. The difference of the parameters was considered to be statistically significant with р<0.05. In case the data were available, 2×2 tables were compiled to derive sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and cutoff level of four markers. The area under the receiver operating characteristic (ROC) curve was used to deduce the diagnostic accuracies of them. Results. No statistical differences exist in the gestational age, body weight or gender signs of the respective groups. The critically ill neonates from group I had serious disorders in the first week of their life. Fifteen (30.0%) newborns had signs of moderate asphyxia, 3 (6.0%) had severe asphyxia, 8 (16.0%) had meconium aspiration, 10 (20.0%) had moderate hypoxic-ischemic encephalopathy (HIE), and 14 (28.0%) had severe HIE. Most newborns in this group had clinical signs of multiple organ dysfunction syndrome (MODS): all of them had severe respiratory failure, 12 (24.0%) had cardiovascular failure, 9 (18.0%) had hemorrhagic syndrome, 6 (12.0%) had seizures, 5 (10.0%) had anemia, and 3 (6.05%) had necrotising enterocolitis. In group II, 8 (17.8%) newborns had signs of moderate asphyxia, 12 (26.7%) had severe asphyxia (pII-III<0.05), 9 (20.0%) had meconium aspiration, 6 (13.3%) had moderate HIE, and 10 (22.2%) had severe HIE. MODS occurred in all critically ill full-term neonates with AKI. Severe respiratory failure was found in all 45 (100.0%) patients in group II, cardiovascular failure in 31 (68.9%; pII-III<0.05), hemorrhagic syndrome in 9 (20.0%), seizures in 9 (20.0%), and anaemia in 8 (17.8%). 8 (17.8%) neonates with AKI developed necrotising enterocolitis. Certain association between AKI and severe asphyxia, cardiovascular failure, and necrotising enterocolitis was found. The results of measurement of biochemical serum and urine markers are presented in Tab. 1. AKI formation in term children is accompanied by total disorders in the functioning of glomerular and tubular renal apparatus. It was evidenced by statistically much higher levels of SCr, SCysC and Uα1-MG in children of the ІІ group as compared to the children from the І group of the study.