A novel urinary biomarker profile to identify acute kidney injury (AKI) in critically ill neonates: a pilot study

Abstract

Background The goal of this study was to assess the value of a urinary biomarker profile comprised of Neutrophil Gelatinase-associated Lipocalin (NGAL), Fibroblast Growth Factor-2 (FGF-2), and Epidermal Growth Factor (EGF), to detect acute kidney injury (AKI) in critically ill neonates. Methods We conducted a prospective cohort pilot study of at-risk neonates treated in a level IIIC neonatal intensive care unit (NICU) with therapeutic hypothermia (HT) (n = 25) or extracorporeal membrane oxygenation (ECMO) (n=10). Urine was collected at baseline, 48 hours of illness, and > 24 hours post recovery of their corresponding treatments. Control samples were collected from 27 healthy newborns. The data were expressed as urinary concentrations and values normalized for urinary creatinine. AKI was defined as the presence of oliguria >24 hours and/or elevated serum creatinine (SCr), or the failure to improve the estimated creatinine clearance (eCCL) by >50% post recovery. Non-parametric statistical tests and ROC analyses were used to interpret the data. Results Fifteen at risk newborns had AKI. In the first 48 hours of illness, the urinary levels of NGAL and FGF-2 had high sensitivity but poor specificity to identify neonates with AKI. At recovery, low urinary EGF levels identified neonates with AKI with a sensitivity of 74% and specificity of 84%. Overall, in the early stages of a critical illness, the urinary levels of NGAL and FGF-2 were sensitive, but not specific, to identify neonates at risk of AKI. Low EGF levels post-recovery, identified critically ill neonates with AKI. Conclusions These findings require validation in larger prospective studies.

A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy

“…The trough levels of gentamicin were measured in samples drawn 30 min before the daily doses of gentamicin were given. In a separate prospective study involving a subset ( n = 25) of patients enrolled in the current study and 27 healthy controls, urinary biomarkers were assessed during the first week of life as described previously [26]. …”

“…The third group, named the delayed rise in eCrCl (DReCrCl) group, included the remaining newborns who failed to increase their eCrCl by >50 % from birth to the 7th day of life and/or showed elevated SCr values at this time point. This eCrCl cutoff point was associated with changes in urinary biomarkers of AKI in newborns with HIE [26] and may be analogous to the pRIFLE injury criteria, which require an eCrCl decrease of 50 %, and correlates with a worse clinical outcome of critically ill children [11]. …”

“…Urine output was measured according to the NICU standard protocol of care [26]. SCr was measured using the kinetic Jaffe method performed on the Siemens Dimension RXL Chemistry Analyzer (Siemens Healthcare, Erlangen, Germany) at the Children’s Hospital central laboratory.…”

“…The SCr measurements done in control samples from healthy newborns were within the normal range. The urinary levels of neutrophil associated gelatinase lipocalin (NGAL) and epidermal growth factor (EGF) were measured using enzyme-linked-immunoabsorbent assay as described in detailed in our previous studies [26, 28]. …”

Acute Kidney Injury Urine Biomarkers in Very Low-Birth-Weight Infants

“…Prior literature has shown that in premature infants without AKI, urine proteins will be highest among those with the lowest GA, probably because of the passive loss of proteins in the context of immature tubular function (6)(7)(8). Previously, we (7) and others (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) have published data on the ability of urine biomarkers to predict AKI in neonates; however, these studies are limited by the size of the cohort or the use of nested case-control methods, with most of these studies evaluating only one biomarker. In addition, previous studies were subject to risk of misclassification bias, given that many infants had only a few SCr levels measured to determine AKI.…”