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

Abstract

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.

Impact of Gestational Age and Birth Weight on Amikacin Clearance on Day 1 of Life

“…We found a positive correlation between amikacin clearance and GA, as has been described for aminoglycosides (18,20,(35)(36)(37)(38)(39). The absolute value of amikacin clearance (0.61 ml/kg per min) is comparable to previously reported values (0.52 to 0.6 ml/kg per min (17)(18)(19)40). Also, the distribution volume of amikacin was similar to previously reported values of 0.58 L/kg (18) and 0.59 L/kg (17).…”

“…Previously, the clearance of amikacin was used as a marker of GFR in neonates (17)(18)(19)(20) because aminoglycoside clearance correlates well with GFR (21). Amikacin is often used in neonates in whom perinatal infection is suspected, and amikacin levels are routinely monitored.…”

Factors affecting postnatal changes in serum creatinine in preterm infants with gestational age <32 weeks

“…22 We have also found that in infants with hsPDA, SeCr increase preceded ibuprofen administration, this suggesting that a renal impairment because of PDA and/or associated conditions exists before starting NSAID therapy. Concerning this point, many studies demonstrated that prophylactic or therapeutic ibuprofen, as with other cyclooxygenase inhibitors, may not be exempt from causing renal adverse effects, [23][24][25] but few investigations have explored the effect on renal function of PDA before and independently from ibuprofen treatment. Vanpée et al 26 showed that sick VLBW infants having a PDA and requiring mechanical ventilation had lower creatinine clearances and significantly higher fractional sodium excretion than controls; however, their study also included few infants who had received NSAID for ductus closure before evaluating renal function.…”

Safety of opioid patch initiation in Australian residential aged care

“…NsNSAIDs affect renal blood flow, glomerular filtration and renal drug clearance (Allegaert, Vanhole et al, 2005). Renal failure in association with nsNSAID use has occurred in neonates (Andreoli, 2004) and older children (Taber & Mueller, 2006), usually in the setting of other haemodynamic compromise.…”

“…Neonatal bolus and short-term use for patent ductus arteriosus closure can produce pulmonary hypertension and alterations in cerebral (Naulaers et al, 2005), gastrointestinal and renal blood flow (Allegaert, Vanhole et al, 2005;Aranda & Thomas, 2006). Relative effects of indomethacin (indometacin) and ibuprofen on the risk of intraventricular haemorrhage continue to be debated (Aranda et al, 1997;Ment et al, 2004).…”