Abstract
Tocolysis with nonsteroidal anti-inflammatory drugs (NSAIDs) has been widely accepted for several years. Recently, the use of the cyclooxygenase-2 (COX2) preferential NSAID nimesulide has been proposed. However, data reporting neonatal acute renal failure or irreversible end-stage renal failure after maternal ingestion of nimesulide question the safety of this drug for the fetus and the neonate. Therefore, this study was designed to define the renal effects of nimesulide in newborn rabbits. Experiments were performed in 28 newborn rabbits. Renal function and hemodynamic parameters were measured using inulin and para-aminohippuric acid clearances as markers of GFR and renal blood flow, respectively. After a control period, nimesulide 2, 20, or 200 μg/kg was given as an i.v. bolus, followed by a 0.05, 0.5, or 5 μg · kg−1 · min−1 infusion. Nimesulide administration induced a significant dose-dependent increase in renal vascular resistance (29, 37, and 92%, respectively), with a concomitant decrease in diuresis (−5, −23, and −44%), GFR (−12, −23, and −47%), and renal blood flow (−23, −23, and −48%). These results are in contrast with recent reports claiming that selective COX2 inhibition could be safer for the kidney than nonselective NSAIDs. These experiments confirm that prostaglandins, by maintaining renal vasodilation, play a key role in the delicate balance regulating neonatal GFR. We conclude that COX2-selective/preferential inhibitors thus should be prescribed with the same caution as nonselective NSAIDs during pregnancy and in the neonatal period.
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Abbreviations
- AQP2:
-
aquaporin 2
- CH2O:
-
free-water clearance
- COX:
-
cyclooxygenase
- FF:
-
filtration fraction
- HR:
-
heart rate
- MAP:
-
mean arterial blood pressure
- NSAID:
-
nonsteroidal anti-inflammatory drug
- PAH:
-
para-aminohippuric acid
- PG:
-
prostaglandin
- RBF:
-
renal blood flow
- RVR:
-
renal vascular resistance
- UV:
-
urine flow rate
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Acknowledgements
We thank M. Julita and M. Thonney Viani for skillful technical help and valuable contributions in the laboratory.
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Supported by the Swiss National Science Foundation (grant nos. 3200-052463.97/1 and 3200-064041.00).Presented in part at the 7th Congress of the European Society for Developmental, Perinatal & Pediatric Pharmacology, Limassol, Cyprus, November 2001; and at the 36th Annual Meeting of the European Society for Pediatric Nephrology, Bilbao, Spain, September 2002.
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Prévot, A., Mosig, D., Martini, S. et al. Nimesulide, a Cyclooxygenase-2 Preferential Inhibitor, Impairs Renal Function in the Newborn Rabbit. Pediatr Res 55, 254–260 (2004). https://doi.org/10.1203/01.PDR.0000100904.17064.47
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DOI: https://doi.org/10.1203/01.PDR.0000100904.17064.47
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