The adverse renal effects of prostaglandin-synthesis inhibitors in the newborn rabbit.
Nonsteroidal anti-inflammatory drugs are frequently used during pregnancy (premature labor, polyhydramnios) and the immediate postnatal period (closure of patent ductus arteriosus). This article evaluates the renal effect of 3 nonspecific COX inhibitors (aspirin, indomethacin, and ibuprofen) in newborn rabbits. Five groups of anesthetized, ventilated, normoxemic 6-day-old rabbits (n = 52) were administered intravenous aspirin (40 mg/kg), indomethacin (2 mg/kg), and ibuprofen (0.02, 0.2, 2.0 mg/kg, respectively). Renal function and hemodynamics as assessed by inulin and para-aminohippuric acid clearances were measured before and in the hour after drug administration. In all groups of animals, the nonselective COX inhibitors induced an increase in renal vascular resistance and a consequent decrease in glomerular filtration rate and renal blood flow. Urine flow rate decreased significantly in all groups, except in the group receiving the lowest dose of ibuprofen. In newborn rabbits, aspirin, indomethacin, and ibuprofen induced intense renal vasoconstriction, which resulted in impaired renal function. This observation illustrates the major renal protective role played by the vasodilatory prostaglandins during the neonatal period, when the kidney is perfused at very low perfusion pressure. We conclude that all COX inhibitors should be administered with the same caution to the preterm neonate.
Guignard
Jean-Pierre
JP
Renal Unit, Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Jean-Pierre.Guignard@chuv.hospvd.ch
D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007052:Ibuprofen / Q000009:adverse effects; D007213:Indomethacin / Q000009:adverse effects; D007444:Inulin / Q000502:physiology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D011817:Rabbits; D010130:p-Aminohippuric Acid / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007444:Inulin; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin; D010130:p-Aminohippuric Acid