Urine Biomarkers Predict Acute Kidney Injury and Mortality in Very Low Birth Weight Infants

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
The Journal of pediatrics (Impact Factor: 3.79). 07/2011; 159(6):907-12.e1. DOI: 10.1016/j.jpeds.2011.05.045
Source: PubMed


To test the hypothesis that noninvasive urinary biomarkers may improve early identification, differentiate causes, and predict outcomes of acute kidney injury (AKI) in very low birth weight subjects.
We performed 2 nested case-control studies to compare the ability of 6 urine biomarkers to predict AKI (rise in serum creatinine of at least 0.3 mg/dL) and mortality (death before 36 weeks postmenstrual age).
Compared to subjects without AKI (n = 21), those with AKI (n = 9) had higher maximum neutrophil gelatinase-associated lipocalin (OR = 1.2 [1.0, 1.6]; P < .01; receiver operator characteristics [ROC] area under the curve [AUC] = .80) and higher maximum osteopontin (OR = 3.2 [1.5, 9.9]; P < .01; ROC AUC = 0.83). Compared with survivors (n = 100), nonsurvivors (n = 23) had higher maximum kidney injury molecule 1 (OR = 1.1 [1.0, 1.2]; P < .02; ROC AUC = 0.64) and higher maximum osteopontin (OR = 1.8 (1.2, 2.7); P < .001; AUC of ROC = 0.78). The combination of biomarkers improved predictability for both AKI and mortality. Controlling for gestational age and birth weight did not affect results considerably.
Urinary biomarkers can predict AKI and mortality in very low birth weight infants independent of gestational age and birth weight.

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    • "In the only study evaluating OPN in neonatal population [43], a nested case-control study with 30 patients (only 9 with AKI) showed that AKI newborns had greater OPN values than controls. Prospective studies are lacking to ascertain OPN value in predicting neonatal AKI. "
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    ABSTRACT: In the past 10 years, great effort has been made to define and classify a common syndrome previously known as acute renal failure and now renamed "acute kidney injury (AKI)." Initially suggested and validated in adult populations, AKI classification was adapted to the pediatric population and recently has been modified for the neonatal population. Several studies have been performed in adults and older children using this consensus definition, leading to improvement in the knowledge of AKI incidence and epidemiology. In spite of these advances, the peculiar renal pathophysiology of critically ill newborn patients makes it difficult to interpret urine output (UO) and serum creatinine (SCr) levels in these patients to diagnose AKI. Also, new urine biomarkers have emerged as a possible alternative to diagnose early AKI in the neonatal population. In this review, we describe recent advances in neonatal AKI epidemiology, discuss difficulties in diagnosing AKI in newborns, and show recent advances in new AKI biomarkers and possible long-term consequences after AKI episode.
    Full-text · Article · Mar 2014
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    • "Some studies have proposed creatinine cut-off values of 1.1 mg/dL to 2 mg/dL after 48 hours, or up to 1.3 mg/dL after 60 hours of age [1,2,13]. Others have proposed definitions based on lack of the initial decrease in serum creatinine levels [14,15]; or conversely, on increased serum creatinine levels above the 99th interval limit based on control studies [16]. More recently, Askenazy et al. proposed an increase in serum creatinine of 0.3 mg/dL, according to the definition of the AKIN (Acute Kidney Injury Network) [15-17]. "
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    ABSTRACT: Renal failure in neonates is associated with an increased risk of mortality and morbidity. But critical values are not known. To define critical values for serum creatinine levels by gestational age in preterm infants, as a predictive factor for mortality and morbidity. This was a retrospective study of all preterm infants born before 33 weeks of gestational age, hospitalized in Nantes University Hospital NICU between 2003 and 2009, with serum creatinine levels measured between postnatal days 3 to 30. Children were retrospectively randomized into either training or validation set. Critical creatinine values were defined within the training set as the 90(th) percentile values of highest serum creatinine (HSCr) in infants with optimal neurodevelopmental at two years of age. The relationship between these critical creatinine values and neonatal mortality, and non-optimal neural development at two years, was then assessed in the validation set. The analysis involved a total of 1,461 infants (gestational ages of 24-27 weeks (n=322), 28-29 weeks (n=336), and 30-32 weeks (803)), and 14,721 creatinine assessments. The critical values determined in the training set (n=485) were 1.6, 1.1 and 1.0 mg/dL for each gestational age group, respectively. In the validation set (n=976), a serum creatinine level above the critical value was significantly associated with neonatal mortality (Odds ratio: 8.55 (95% confidence interval: 4.23-17.28); p<0.01) after adjusting for known renal failure risk factors, and with non-optimal neurodevelopmental outcome at two years (odds ratio: 2.06 (95% confidence interval: 1.26-3.36); p=0.004) before adjustment. Creatinine values greater than 1.6, 1.1 and 1.0 mg/dL respectively at 24-27, 28-29, 30-32 weeks of gestation were associated with mortality before and after adjustment for risk factors, and with non-optimal neurodevelopmental outcome, before adjustment.
    Full-text · Article · Dec 2013 · PLoS ONE
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    • "The same group has also reported that urine biomarkers (again including NGAL and KIM-1) had good predictive value for AKI and mortality in very low birth weight infants. [32]. "
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    ABSTRACT: Premature infants are frequently exposed to aminoglycoside antibiotics. Novel urinary biomarkers may provide a non-invasive means for the early identification of aminoglycoside-related proximal tubule renal toxicity, to enable adjustment of treatment and identification of infants at risk of long-term renal impairment. In this proof-of-concept study, urine samples were collected from 41 premature neonates (≤ 32 weeks gestation) at least once per week, and daily during courses of gentamicin, and for 3 days afterwards. Significant increases were observed in the three urinary biomarkers measured (Kidney Injury Molecule-1 (KIM-1), Neutrophil Gelatinase-associated Lipocalin (NGAL), and N-acetyl-β-D-glucosaminidase (NAG)) during treatment with multiple courses of gentamicin. When adjusted for potential confounders, the treatment effect of gentamicin remained significant only for KIM-1 (mean difference from not treated, 1.35 ng/mg urinary creatinine; 95% CI 0.05-2.65). Our study shows that (a) it is possible to collect serial urine samples from premature neonates, and that (b) proximal tubule specific urinary biomarkers can act as indicators of aminoglycoside-associated nephrotoxicity in this age group. Further studies to investigate the clinical utility of novel urinary biomarkers in comparison to serum creatinine need to be undertaken.
    Full-text · Article · Aug 2012 · PLoS ONE
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