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

Abstract

Background and objectives Serum creatinine (SCr)-based AKI definitions have important limitations, particularly in very low-birth-weight (VLBW) neonates. Urine biomarkers may improve our ability to detect kidney damage. We assessed the association between 14 different urine biomarkers and AKI in VLBW infants.Design, setting, participants, & measurements We performed a prospective cohort study on 113 VLBW infants (weight #1200 g or ,31 weeks' gestation) admitted to a regional neonatal intensive care unit at the University of Alabama at Birmingham between February 2012 and June 2013. SCr was measured on postnatal days 1, 2, 3, and 4 and was combined with clinically measured SCr to determine AKI according to Kidney Disease Improving Global Outcomes AKI definition (increase in SCr $0.3 mg/dl or $50% increase from previous lowest value). Urine was collected on the first 4 days (average number of urine collections, 3; range, 1-4). The maximum urine biomarkers and urine biomarker/creatinine levels were calculated for 12 urine biomarkers, and the minimum urine biomarker and biomarker/creatinine levels were assessed for two urine biomarkers. We compared these values between infants with and those without AKI. Ideal cutoffs, area under the receiver-operating characteristic curve , and area under the curve adjusted for gestational age were calculated.Results Cumulative incidence of AKI during the first 2 postnatal weeks was 28 of 113 (25%). Infants with AKI had higher maximum levels of urine cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, clusterin, and a glutathione S-transferase (2.0, 1.8, 1.7, 1.7, and 3.7 times higher, respectively) than infants without AKI. In addition, infants with AKI had lower minimum levels of epithelial growth factor and uromodulin than those without AKI (1.4 and 1.6 times lower, respectively). Most but not all participants had their maximum (or minimum) biomarker values preceding AKI. These associations remained after adjustment for gestational age.Conclusions Urine biomarkers measured in the first 4 days of life are associated with AKI during the first postnatal weeks. Further evaluations are necessary to determine whether these biomarkers can predict important clinical outcomes. In addition, intervention studies that use biomarkers to stratify enrollment groups are needed before bedside evaluations can be incorporated into care.

Alterations in Serum Lead Levels Following Packed Red Blood Cells Transfusions to Preterms Admitted to Neonatal Intensive Care Unit at Cairo University Pediatric Hospital

“…Multivariate analysis revealed that blood creatinine level after transfusion was the best predictor of BLL% change. This goes in consonance with similar studies which proved that pathologies like acute kidney injury are best predicted by serum creatinine levels which affects up to 20% of critically ill neonates and is associated with an increased risk of mortality (15,16). On the other hand, another studies argued that although blood creatinine is the most commonly used endogenous marker for GFR, it is not the most adequate marker for the neonatal population.…”

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“…Identification of new biomarkers predicting nephrotoxicity and enabling the early detection of AKI could improve patient outcome [139,147,400,401]. …”

“…A neonatal KDIGO classification has been proposed, but serum creatinine may not be reliable as it reflects maternal creatinine and is also dependent on maturity of renal tubule function [136]. Cystatin C levels may reflect renal function better than creatinine, and various biomarkers are being investigated as a tool to detect AKI early [139,140]. The major risk factors for neonatal AKI are preterm birth, LBW, reduced nephron numbers, critical illness, and nephrotoxin exposure [58,136,141,142,143].…”

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“…Creatinine values were acquired using a mass spectrometry based method run in the University of Alabama at Birmingham clinical laboratory. NGAL values were acquired using a Kidney Injury Panel 5 Human kit (KIP-5) microtiter plate assay (Meso Scale Discovery, Rockville, MD, USA) [22]. Insulin levels were measured using the ACCESS ultrasensitive insulin assay kit from Beckman Coulter (Brea, CA, USA).…”