Impact of gestational age, sex, and postnatal age on urine biomarkers in premature neonates

Saeidi, Behtash; Koralkar, Rajesh; Griffin, Russell; Halloran, Brian; Ambalavanan, Namasivayam; Askenazi, David

doi:10.1007/s00467-015-3129-z

Cited by 49 publications

(55 citation statements)

References 21 publications

(21 reference statements)

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“…We could not assess the impact of postnatal age on urinary biomarkers. Saeidi et al (22) showed that postnatal age affects urine biomarkers measured in the first 4 d of life in preterm infants without AKI. The nested casecontrol study design was not intended to assess the incidence of AKI; it has the advantage of cost and effort reduction with relatively minor loss in statistical efficiency compared with the full-cohort approach (23).…”

Section: Discussionmentioning

confidence: 99%

Early urinary biomarkers of acute kidney injury in preterm infants

et al. 2016

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Background: Acute kidney injury (AKI) in the neonatal intensive care setting is multifactorial and is associated with significant morbidity and mortality. This study evaluates the utility of novel urinary biomarkers to predict the development and/or severity AKI in preterm infants. Methods: We performed a case-control study on a prospective cohort of preterm infants (<32 wk), to compare seven urine biomarkers between 25 infants with AKI and 20 infants without AKI. results: Infants with AKI had significantly higher neutrophil gelatinase-associated lipocalin (NGAL) (median, control (CTRL) vs. AKI; 0.598 vs. 4.24 µg/ml; P < 0.0001). In contrast, urinary epidermal growth factor (EGF) levels were significantly lower in infants who developed AKI compared to controls (median, CTRL vs. AKI; 0.016 vs. 0.006 µg/ml; P < 0.001). The area under the curve (AUC) for NGAL for prediction of stage I AKI on the day prior to AKI diagnosis (day-1) was 0.91, and for the prediction of stage II/III, AKI was 0.92. Similarly, urine EGF was a predictor of renal injury on day -1 (AUC: 0.97 for stage I and 0.86 for stage II/III AKI). conclusion: Urinary biomarkers may be useful to predict AKI development prior to changes in serum creatinine (SCr) in preterm infants.

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Section: Discussionmentioning

confidence: 99%

Early urinary biomarkers of acute kidney injury in preterm infants

et al. 2016

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“…In addition, acute changes in fluid status, which occur during this time period, may have an important effect on SCr values (4,5). Fortunately, urine protein biomarkers show promise of someday being able to help diagnose AKI early in the disease process by noninvasively measuring specific urine proteins (6). Improving the ability to reliably detect AKI would have important implications in the ability to care for critically ill neonates and will also improve the ability to perform clinical research.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Askenazi

Koralkar

Patil

et al. 2016

CJASN

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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.

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“…Urinary biomarkers demonstrated a significant change 24 h prior to contemporary creatinine-based neonatal AKI definition [28]. It is particularly important to recognize the differences in omics biomarkers across different gestational ages, postnatal days, and fluid balance status when designing future validation studies [29][30][31][32].…”

Section: Drug-induced Nephrotoxicitymentioning

confidence: 99%

Metabolomics in Neonatology

Hanna¹,

Brophy²

2016

Metabolomics - Fundamentals and Applications

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Throughout recent decades, the incidence of preterm birth has risen worldwide, and although the majority of preterm neonates now survive infancy, many suffer from debilitating morbidities in the short term and/or increased disease risks in the long term. Traditional diagnostic biomarkers suffer from considerable confounders, limiting their use in the early identification of diseases. There is a need to develop novel biomarkers that can identify, in real time, the evolution of organ dysfunction in an early diagnostic, monitoring, and prognostic fashion. Use of "omics," particularly metabolomics, may provide valuable information regarding functional pathways underlying different pathologies and prediction of clinical outcomes. The emerging knowledge generated by the application of metabolomics in neonatology provides new insights that can help to identify markers of early diagnosis, disease progression, response to treatment, and new therapeutic targets. In this chapter, we review the current knowledge of different metabolomics technologies in neonatal-perinatal medicine, including biomarker discovery, defining as yet unrecognized biologic therapeutic targets, and linking of metabolomics to relevant standard indices and long-term outcomes.

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Impact of gestational age, sex, and postnatal age on urine biomarkers in premature neonates

Cited by 49 publications

References 21 publications

Early urinary biomarkers of acute kidney injury in preterm infants

Early urinary biomarkers of acute kidney injury in preterm infants

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

Metabolomics in Neonatology

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