Biomarkers in neonates receiving potential nephrotoxic drugs.

OBJECTIVE: Novel biomarkers, such as kidney injury molecule-1 (KIM-1), cystatin, and neutrophil gelatinase-associated lipocalin (NGAL) were shown to predict acute kidney injury (AKI) earlier than serum creatinine in critically ill. We carried out the present study to evaluate these biomarkers in addition to conventional in our neonates. PATIENTS AND METHODS: We recruited 70 neonates of various gestational age groups receiving one or more potential nephrotoxic drug/s. Daily urine samples were collected for estimating KIM-1, cystatin, and NGAL. Modified neonatal kidney disease improving global outcomes (mKDIGO) classification was used in defining AKI. RESULTS: A significant trend in increased urine concentrations of KIM-1, cystatin, and NGAL were observed as we proceed from term to preterm categories. Strong positive correlation was observed between urine albumin and urine albumin creatinine ratio (ACR), and strong negative correlations between urine creatinine and urine cystatin, and between urine creatinine with urine NGAL. A moderate positive correlation was observed between urine KIM-1 and urine cystatin, between urine KIM-1 and urine NGAL, and between urine cystatin and urine NGAL; and a moderate negative correlation was observed between urine creatinine and urine KIM-1. Seven neonates met the mKDIGO criteria for AKI and ROC plot revealed that baseline KIM-1 and NGAL can significantly predict possible drug-induced AKI in neonates. CONCLUSIONS: Urine KIM-1, cystatin, and NGAL are significantly correlated with several other conventional biomarkers that reflect renal function in critically ill neonates. Baseline urine KIM-1 and NGAL concentrations can predict the AKI following potential nephrotoxic drug use in this population.

Intravenous frusemide does not interact pharmacodynamically with acetaminophen in critically ill preterm neonates with patent ductus arteriosus.

OBJECTIVE: Evidence is controversial regarding the effect of concomitant frusemide with acetaminophen therapy in neonates with patent ductus arteriosus (PDA). PATIENTS AND METHODS: Critically ill neonates diagnosed with hemodynamically significant PDA by echocardiography and receiving intravenous acetaminophen were recruited. Dosing regimens of frusemide, and acetaminophen, and the sizes of ductus arteriosus following treatment, were evaluated. RESULTS: Fifty-one neonates were recruited. Forty-six (90.2%) had moderate-sized, and five (9.8%) had large-sized ductus arteriosus. Forty (78.4%) neonates had a successful closure. Twenty-four received concomitant frusemide with a median (range) cumulative dose of 3 (0.8-13) mg; duration of 2 (1-13) days; and a fraction of overlapping days with acetaminophen therapy of 0.4 (0.2-1). Twenty-one (87.5%) neonates that received frusemide had a successful ductal closure compared to 70.4% of those without (p >0.05). CONCLUSIONS: We did not observe any significant influence in the outcomes of acetaminophen therapy with concomitant frusemide in preterm neonates with PDA.