Nonselective cyclo-oxygenase inhibitors and glomerular filtration rate in preterm neonates

The adverse effects of nonselective cyclo-oxygenase (COX) inhibitors on the immature kidney have been described in newborn rabbits, but it is much more laborious and difficult to study its relative impact on renal function in human neonates. Amikacin clearance was therefore used as surrogate marker to study the impact of nonselective COX-inhibitors on glomerular filtration rate. Clinical characteristics and amikacin clearance of infants on respiratory support were retrospectively collected. Results in neonates in whom either ibuprofen-lysine or acetylsalicylic acid was administered prophylactically to induce closure of a patent asymptomatic ductus arteriosus were compared to infants not cotreated with any COX-inhibitor (Mann-Whitney U-, chi-square tests). Amikacin clearance was calculated in 142 infants, of whom 50 were cotreated with ibuprofen and 33 with acetylsalicylic acid. There were no significant differences in clinical characteristics between the three groups. Compared to controls (0.52, range 0.09-2.33 ml/kg/min), a significant similar decrease in amikacin clearance in infants cotreated with ibuprofen (0.38, range 0.13-0.80 ml/kg/min, p < 0.01) or acetylsalicylic acid (0.38, range 0.13-0.78 ml/kg/min, p < 0.01) was demonstrated. Using amikacin clearance as marker, a significant and similar reduction in glomerular filtration rate was documented in preterm infants cotreated with ibuprofen or acetylsalicylic acid.