Abstract
BACKGROUND: Early diagnosis of Acute Kidney Injury (AKI) in neonates is a complex challenge. Novel urinary biomarkers such as uNGAL and TIMP-2*IGFBP7 may be helpful for predicting AKI earlier than changes in serum creatinine (sCr) and urinary output (UOP) in the neonatal period. uNGAL is a marker of tubular injury and its concentration rises immediately after AKI, while the proteins TIMP-2 and IGFBP7 jointly participate in the G1 phase cell cycle arrest processes and their tubular expression and urinary excretion increase in response to kidney damage. The aim of this study is to determine urinary concentrations of uNGAL and TIMP-2*IGFBP7 in term and preterm newborns and to evaluate their predictive role of AKI. METHODS: Forty-two heathy term neonates and twenty-six preterm infants were prospectively recruited at the NICU of Policlinico in Bari, Italy. uNGAL and TIMP-2*IGFBP7 were measured in fresh urinary samples collected via perineal bag either before discharge (term neonates) or over the first week of life (preterm neonates). RESULTS: In term neonates median uNGAL and TIMP-2*IGFBP7 concentrations were 41.40 ng/ml (IQR 20.25-74.5) e 0.22 (ng/ml)(2)/1000 (IQR 0.14-0.34), respectively. In preterm infants without AKI, uNGAL median concentrations over the first week of life ranged between 10 and 16 ng/ml, whereas median concentration of TIMP-2*IGFBP7 ranged between 0.05 and 0.08 (ng/ml)(2)/1000. Preterm infants who developed AKI during the first week of life had significantly higher uNGAL median concentrations compared to preterm infants without AKI (148.5 vs. 10.0, p = 0.04; 324.0 vs. 15.75, p = 0.02; 318.0 vs. 16.0 ng/ml, p = 0.04). Conversely, TIMP-2*IGFBP7 did not significantly increase in preterm infants with AKI. Preterm female neonates without AKI had significantly higher uNGAL than male neonates (46.5 vs. 10.0 ng/ml; Mann-Whitney U-test, p =0.013). CONCLUSIONS: Our data show that uNGAL could be more useful than TIMP-2*IGFBP7 for early detection of AKI in preterm newborns. Further studies are needed to evaluate the role of both biomarkers during AKI and their relationship with gender, gestational age and birth weight.