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

Abstract

Background. 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.