Baseline Values of Candidate Urine Acute Kidney Injury Biomarkers Vary by Gestational Age in Premature Infants

Askenazi, David; Koralkar, Rajesh; Levitan, Emily B.; Goldstein, Stuart L.; Devarajan, Prasad; Khandrika, Srikrishna; Mehta, Ravindra L.; Ambalavanan, Namasivayam

doi:10.1203/pdr.0b013e3182275164

Cited by 130 publications

(150 citation statements)

References 31 publications

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“…Chen et al (19) reported lower urine EGF levels in infants with severe perinatal asphyxia compared with controls, suggesting that EGF may play a role in the repair of acute renal injury after asphyxia. We controlled for birth weight as a potential confounder in evaluating the association between urine biomarkers and AKI to ensure that the detected changes in these biomarkers are not simply a reflection of prematurity (20). Askenazi et al (21) demonstrated that urinary biomarkers can predict AKI and mortality in very-low-birth-weight infants independent of gestational age and birth weight.…”

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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“…Another study has examined the role of gestational age within the urinary proteome looking at pre-selected markers. Urinary levels of neutrophil gelatinase-associated lipocalin, osteopontin, and beta-2 microglobulin decreased as the gestational age of the infant increased (26). Our study used a targeted approach to identifying markers of renal development and we have discovered a number of novel markers that may play a role in renal development or renal injury.…”

Section: Articlesmentioning

confidence: 94%

“…This study reveals marked differences in urinary cytokines between infants undergoing completion of nephrogenesis and those undergoing normal postnatal renal maturation. Gestational and postnatal age affect the urinary levels of many proteins and cytokines (26). Another study has examined the role of gestational age within the urinary proteome looking at pre-selected markers.…”

Section: Articlesmentioning

confidence: 99%

Evolution of the urinary proteome during human renal development and maturation: variations with gestational and postnatal age

et al. 2012

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Background: Low birth weight is associated with deficits in nephron number in the infant kidney and increased risk of adulthood hypertension and renal dysfunction. Urinary biomarkers may be potential indicators of renal reserve, but little is known about the influence of gestational and postnatal age on the expression of urinary proteins. The aims of this study were to determine the relationships between selected urinary proteins and renal maturation. We hypothesized that urinary protein patterns would change over time during late nephrogenesis and renal maturation. Methods: Urine samples were collected at birth and over 12 mo from preterm (33-35 wk) and term (38-40 wk) infants. candidate urinary proteins were identified by antibody array and quantified with enzyme-linked immunosorbent assay. results: Preterm infants at birth were found to have relatively elevated levels of insulin-like growth factor binding protein-1, -2, and -6, monocyte chemotactic protein-1, cD14, and sialic acid-binding Ig-like lectin 5. These markers gradually decline to levels similar to those of full-term infants by 2-6 mo of life. In contrast, many urinary markers in healthy full-term infants remain stable over the first year of life. conclusion: Gestational and postnatal age must be considered when evaluating the utility of urinary biomarkers. P remature infants are challenged to adapt to an ex utero environment while organogenesis remains incomplete. In humans, ~60% of nephrons develop during the third trimester (1) with nephrogenesis complete at 32-36 wk gestation (2). Although the kidney continues to mature for an additional 1-2 y, full-term infants have a complete endowment of nephrons, varying widely from 250,000 to 1.8 million per kidney, by 36 wk gestation (2,3) and do not form new nephrons after birth. However, the duration of nephrogenesis and the health of the nephrons in infants born prematurely remain unknown. There appears to be a correlation between gestational age and nephron number in large animal species. Studies in baboons demonstrate a direct correlation between gestational age and nephron number (4). Moreover, prematurely delivered baboons continue to develop nephrons after birth, but the length of gestation inversely correlates with the number of abnormal nephrons (4) (the lower the gestational age the higher the number of abnormal nephrons). There may be a limited window for nephrogenesis to continue postnatally in humans. A single autopsy study has shown that nephrogenesis appears to continue for 40 postnatal days in extremely preterm human infants and then cease (5). A smaller complement of nephrons may not be reflected by renal dysfunction in the preterm infant. However, adults born at a low birth weight, with a reduced number of nephrons, are at increased risk of hypertension, impaired kidney function, and cardiovascular disease (6).As the overall mortality of the premature population decreases, the risk of long-term morbidity in this population emerges (7). Barker and Martyn (8) established a framework for th...

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“…Recent studies have shown that immature neonates have higher concentrations of these biomarkers in the urine. This is probably due to the inability of the immature tubules to reabsorb proteins (6,30,31). There are very few studies that have examined these biomarkers in the neonates.…”

Section: Discussionmentioning

confidence: 99%

Urinary kidney injury molecule-1 rapid test predicts acute kidney injury in extremely low-birth-weight neonates

et al. 2015

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Background:The new urinary and serum biomarkers are discovered and are being investigated. With them we can diagnose acute kidney injury (AKI) faster and more precisely and they also have a significant role in the outcome prediction. Methods: The study included 22 extremely low-birthweight neonates who were hospitalized in the neonatal intensive care units. They were divided into two groups based on serum creatinine (SCr) level-with and without AKI. Detection and quantification of urinary kidney injury molecule-1 (uKIM-1) was done on the third day of life, using commercially available KIM-1 rapid test. Subsequently, measurements were repeated only in subjects who were diagnosed with AKI, at different values of SCr. results: Logistic regression analysis showed that AKI is an independent risk factor for mortality. In a group of neonates with AKI, 50% of neonates administered the KIM-1 rapid test showed positive findings. KIM-1 rapid test was positive in patients with a wide range of SCr levels (range of 78.73-385 µmol/l), but all subjects had oliguria and died in the next 24 h. conclusion: KIM-1 is a significant predictor of death. On the other hand, our study failed to prove that KIM-1 rapid test has any significance for early prediction of AKI.

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Baseline Values of Candidate Urine Acute Kidney Injury Biomarkers Vary by Gestational Age in Premature Infants

Cited by 130 publications

References 31 publications

Early urinary biomarkers of acute kidney injury in preterm infants

Early urinary biomarkers of acute kidney injury in preterm infants

Evolution of the urinary proteome during human renal development and maturation: variations with gestational and postnatal age

Urinary kidney injury molecule-1 rapid test predicts acute kidney injury in extremely low-birth-weight neonates

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