Neonatal acute kidney injury during indomethacin therapy: does it predict ductal closure?

Abstract

Background: Preterm newborns are at risk for patent ductus arteriosus, and non-steroidal anti-inflammatory drugs are often used to facilitate patent ductus arteriosus closure. Acute kidney injury is common in critically ill neonates and may be caused by non-steroidal anti-inflammatory drugs. We sought to describe the incidence of acute kidney injury among preterm infants receiving indomethacin and determine whether acute kidney injury during indomethacin therapy is associated with subsequent patent ductus arteriosus closure.

Methods: Retrospective cohort including neonates < 33 weeks gestational age, admitted to two level IIIb neonatal intensive care units between November 2016 and November 2019, who received indomethacin in the first 2 weeks of life. Acute kidney injury in the 7-day period after treatment was defined by neonatal modified Kidney Disease Improving Global Outcomes (KDIGO) criteria. Patent ductus arteriosus closure was defined clinically and/or via echocardiogram. Clinical characteristics were extracted from medical records. Association between acute kidney injury during treatment and successful closure of patent ductus arteriosus was evaluated using chi-square tests and logistic regression.

Results: One hundred fifty preterm infants were included; acute kidney injury occurred in 8% (all KDIGO Stage 1). Patent ductus arteriosus closed in 52.9% of the non-acute kidney injury group and 66.7% of the acute kidney injury group (p = 0.55). Serum creatinine was checked a mean of 3.1 times in the acute kidney injury group and 2.2 times in the non-acute kidney injury group. There was no difference in survival.

Conclusion: We found no association between acute kidney injury during indomethacin therapy and patent ductus arteriosus closure. Paucity of serum creatinine values likely underdiagnosed acute kidney injury. Surveillance of kidney function during indomethacin therapy using more sensitive renal biomarkers may better identify infants who develop acute kidney injury in the context of non-steroidal anti-inflammatory drug use.

Keywords: Acute kidney injury (AKI); Indomethacin; Neonatal; Patent ductus arteriosus (PDA).