Indomethacin and Renal impairment in neonates

Abstract

Renal impairment occurs in neonates receiving indomethacin for treatment of patent ductus arteriosus. Inhibition of cyclooxygenase within the neonatal kidney results in decreased prostaglandin synthesis and consequent reduction in renal perfusion. Indomethacin has been reported to cause short-term reduction in glomerular filtration that resolves after cessation of the drug. There is little information on the long-term effects of postnatal exposure to indomethacin. The aim of this study was to determine the incidence of renal impairment in infants treated with indomethacin in a single center, to determine whether there is evidence of renal impairment on day 30 or at discharge, and to identify risk factors for renal impairment. In a retrospective study, infants of less than 30 weeks completed gestation who received indomethacin to close the ductus arteriosus were matched with infants of the same gestation, birth weight, and severity of illness. Serum creatinine and glomerular filtration rates (GFR) were obtained prior to commencing indomethacin and on days 2, 7, and 30 following indomethacin administration. Acute renal failure was defined as an increase in creatinine of greater than 25%. Of those infants who were less than 30 weeks completed gestation, 24% had acute renal failure following indomethacin administration. There was a significant elevation in serum creatinine on day 2 and day 7 (P<0.0001, P=0.002) and a decrease in GFR on day 2 and day 7 (P<0.0001, P=0.01) following administration of indomethacin. Renal function had normalized by day 30 or discharge. The incidence of acute renal failure in neonates treated with indomethacin is clinically significant. Renal function returns to normal by day 30. Linear regression found no statistical significance for gestational age, day of indomethacin dosing, Clinical Risk Index for Babies (CRIB) score, and presence of an umbilical artery catheter to confound the effect of indomethacin on renal function.