ABSTRACT
BACKGROUND: Bronchopulmonary dysplasia (BPD) portends lifelong organ impairment and death. Our ability to predict BPD in first days of life is limited, but could be enhanced using novel biomarkers. METHODS: Using an available clinical and urine biomarker database obtained from a prospective 113 infant cohort (birth weight ≤1,200 g and/or gestational age ≤31 wk), we evaluated the independent association of 14 urine biomarkers with BPD/mortality. RESULTS: Two of the 14 urine biomarkers were independently associated with BPD/mortality after controlling for gestational age (GA), small for gestational age (SGA), and intubation status. The best performing protein was clusterin, a ubiquitously expressed protein and potential sensor of oxidative stress associated with lung function in asthma patients. When modeling for BPD/mortality, the independent odds ratio for maximum adjusted urine clusterin was 9.2 (95% CI: 3.3-32.8, P < 0.0001). In this model, clinical variables (GA, intubation status, and SGA) explained 38.3% of variance; clusterin explained an additional 9.2%, while albumin explained an additional 3.4%. The area under the curve incorporating clinical factors and biomarkers was 0.941. CONCLUSION: Urine clusterin and albumin may improve our ability to predict BPD/mortality. Future studies are needed to validate these findings and determine their clinical usefulness.
Subject(s)
Albuminuria/diagnosis , Biomarkers/urine , Bronchopulmonary Dysplasia/urine , Albuminuria/mortality , Birth Weight , Bronchopulmonary Dysplasia/diagnosis , Bronchopulmonary Dysplasia/mortality , Clusterin/urine , Female , Gestational Age , Humans , Infant , Infant, Newborn , Infant, Premature , Infant, Small for Gestational Age , Infant, Very Low Birth Weight , Intensive Care Units, Neonatal , Male , Odds Ratio , Risk FactorsABSTRACT
BACKGROUND: Acute kidney injury (AKI) impairs electrolyte balance, alters fluid homeostasis and decreases toxin excretion. More recent data suggest it also affects the physiology of distant organs. METHODS: We performed a prospective cohort study which invloved 122 premature infants [birth weight (BW) ≤1200 g and/or gestational age (GA) <31 weeks] to determine relationships between AKI and bronchopulmonary dysplasia (BPD)/mortality. Days until oxygen discontinuation was compared between those with and without AKI in survivors who received oxygen for ≥24 h. RESULTS: Acute kidney disease, defined by a rise in serum creatinine (SCr) of ≥0.3 mg/dl or an increase in SCr of ≥150%, occurred in 36/122 (30%) of the premature infants. Those with AKI had a 70% higher risk of oxygen requirement or of dying at 28 days of life [relative risk (RR) 1.71, 95% confidence interval (CI) 1.22-2.39; p < 0.002]. This association remained after controlling for GA, pre-eclampsia, 5 min Apgar score and percentage maximum weight change (max % weight Δ) in the first 4 days (RR 1.45, 95% CI 1.07-1.97); p < 0.02). Similar findings were noted for receipt of mechanical ventilation/death by day 28 (adjusted RR 1.53, 95% CI 1.05-2.22; p < 0.03). Those without AKI were 2.5-fold more likely to come off oxygen [hazard ratio (HR) 1.3-5; p < 0.02) than those with AKI, even when controlling for GA, pre-eclampsia, 5 min Apgar and max % weight Δ (multivariate HR 2.0, 95% CI 0.9-4.0; p < 0.06). CONCLUSIONS: In premature infants, AKI is associated with BPD/mortality. As AKI could lead to altered lung physiology, interventions to ameliorate AKI could improve long-term BPD.
