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: 3.74). 07/2011; 159(6):907-12.e1. DOI: 10.1016/j.jpeds.2011.05.045
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Acute kidney injury (AKI) is associated with increased risk of morbidity and mortality in critically ill children and adults. Neonates remain an understudied group, although previous evidence suggests that this association holds true for them as well. Attention to the issue of neonatal AKI is increasing. New studies in very low-birthweight infants, infants with congenital heart disease who undergo cardiopulmonary bypass, those who receive extracorporeal membrane oxygenation and infants with perinatal depression continue to demonstrate that AKI is common in neonates and associated with increased risk of morbidity and mortality. Additional advances in the field of neonatal AKI include adaptation of modern, categorical AKI definitions, as well as further evaluation of novel urinary biomarkers (e.g., neutrophil gelatinase-associated lipocalin) in this patient group. AKI is an independent risk factor for poor outcomes in critically ill neonates. Our ability to improve outcomes for these patients depends on heightened awareness of this issue both at the bedside as well as in research, commitment to using standardized AKI definitions in order to pool and compare data more effectively and improvement in our diagnostic methods with better AKI biomarkers so that we can identify AKI and intervene much earlier in the disease course.
    Current opinion in pediatrics 01/2012; 24(2):191-6. DOI:10.1097/MOP.0b013e32834f62d5 · 2.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Urinary interleukin-18 and cystatin-C are suggested to be biomarkers for predicting acute kidney injury (AKI). The aims of this study are to examine whether the urinary concentrations of interleukin-18 and cystatin-C vary with gestational age and other factors in non-AKI control neonates, and to determine whether urinary interleukin-18 and cystatin-C can predict AKI development in non-septic critically ill neonates, independently of potential confounders. We enrolled 62 non-septic critically ill neonates. Urine was collected every 48-72 h during the first 10 days of life. Urinary concentration of cystatin-C, but not interleukin-18, decreased with increasing gestational age and body weight, but not with increasing postnatal age in non-AKI control neonates. Both urinary interleukin-18 and cystatin-C were associated with AKI, even after controlling for gestational and postnatal age, birth weight, gender, Apgar score and the score for neonatal acute physiology in non-septic critically ill neonates. Urinary interleukin-18 and cystatin-C had odds ratios of 2.27 and 2.07, and achieved the area under-the-receiver-operating-characteristic curve of 0.72 and 0.92, respectively, for predicting AKI. The urinary concentration of cystatin-C, but not interleukin-18, may decrease with increasing renal maturity. Both urinary interleukin-18 and cystatin-C are independently predictive of AKI in non-septic critically ill neonates.
    Pediatric Nephrology 01/2012; 27(5):851-60. DOI:10.1007/s00467-011-2072-x · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To identify urine biomarkers predictive of acute kidney injury (AKI) in infants admitted to level 2 and 3 neonatal intensive care units with birth weight >2000 g and 5-minute Apgar score ≤ 7. A nested case-control study was performed comparing 8 candidate urine AKI biomarkers in infants with AKI (defined as a rise in serum creatinine of at least 0.3 mg/dL or a serum creatinine elevation ≥ 1.7 mg/dL persisting for 3 days) and 24 infants from the described cohort without AKI. Urine was analyzed for neutrophil gelatinase-associated lipocalin, osteopontin, cystatin C, albumin, β(2) microglobulin, epithelial growth factor, uromodulin (UMOD), and kidney injury molecule 1. Compared with the infants without AKI, those with AKI had higher levels of urine cystatin C (1123 pg/mL [95% CI, 272-4635 pg/mL] vs 90 pg/mL [95% CI, 39-205 pg/mL]; P < .004; area under the receiver operating characteristic curve [AUC] = 0.82), lower levels of UMOD (11.0 pg/mL [95% CI, 5.7-21.4 pg/mL] vs 26.2 pg/mL [95% CI, 17.4-39.4 pg/mL]; P < .03; AUC = 0.77), and lower levels of epithelial growth factor (6.7 pg/mL [95% CI, 4.0-11.3 pg/mL] vs 17.4 pg/mL [95% CI, 12.7-23.8 pg/mL; P = .003; AUC = 0.82). Although the differences were not statistically significant, levels of urine neutrophil-associated gelatinase lipocalin, kidney injury molecule 1, and osteopontin trended higher in infants with AKI. Urinary biomarkers can predict AKI in neonates admitted to level 2 and 3 neonatal intensive care units.
    The Journal of pediatrics 03/2012; 161(2):270-5.e1. DOI:10.1016/j.jpeds.2012.02.007 · 3.74 Impact Factor
Show more