Acute kidney injury among preterm infants receiving non-steroidal anti-inflammatory drugs for patent ductus arteriosus

Abstract

Background: Nonsteroidal anti-inflammatory drugs (NSAID) are a frequently prescribed class of medication in the neonatal intensive care unit (NICU). Hospitalized patients receiving NSAID therapy are at an increased risk of acute kidney injury (AKI). Our primary objective was to reveal AKI epidemiology in NSAID-exposed premature infants admitted to the NICU using a standardized definition.Methods: This retrospective study included infants born at ≤34 weeks gestational age who received NSAID for intraventricular haemorrhage prophylaxis [“prophylaxis group”] or symptomatic treatment for patent ductus arteriosus (PDA) [“treatment group”] between January and December 2014 at British Columbia Women’s Hospital NICU. All available serum creatinine (SCr) and 12-hour urine output (UO) were recorded from admission till day 7 post NSAID exposure. AKI incidence was determined using the modified Kidney Disease: Improving Global Outcomes (KDIGO) classification with an increase in SCr (ΔSCr) (50% rise from prior SCr within 7 days or 26.5 mmol/L rise within 48 hours) and/or UO < 1 mL/kg/hour, excluding the first 24 h of life.Results: We identified 70 eligible subjects, 32 of whom received prophylactic NSAID (prophylaxis group), and 38 received indomethacin or ibuprofen for treatment of symptomatic PDA (treatment group), with an overall AKI incidence of 23% (16/70). The treatment group had a higher proportion of infants with SCr monitoring during the NSAID than the prophylaxis group (87% vs. 13%, p<0.001). Based upon the above defined criteria (fulfilling at least one—either the UO or SCr monitoring criteria), the prophylaxis group had a significantly lower AKI rate compared with the treatment group (9% vs. 34%; p=0.014). Conclusions: AKI incidence is higher in infants treated with NSAID for symptomatic PDA than in those treated prophylactically during the first day of life, based on the criteria applied. However, the burden of AKI may be underestimated in the prophylaxis group due to fewer available SCr values after exposure, and inability to utilize UO criteria in the 1st 24 hours of life. Standardized protocols for monitoring daily SCr and UO after exposure should be implemented for all neonates with NSAID exposure and should be considered to improve AKI recognition.