Indomethacin administered early in the postnatal period results in reduced glomerular number in the adult rat

Background/Aims: Indomethacin and ibuprofen are administered to close a patent ductus arteriosus during active glomerulogenesis. Light and electron microscopic glomerular changes with no change in glomerular number were seen following indomethacin and ibuprofen treatment during glomerulogenesis at 14 days after birth in a neonatal rat model. This present study aimed to determine whether longstanding renal structural changes are present at 30 days and 6 months (equivalent to human adulthood). Methods: Rat pups were administered indomethacin or ibuprofen antenatally on day18-20 (indomethacin 0.5 mg/kg/dose; ibuprofen 10 mg/kg/dose) or postnatally intraperitoneally from day 1 to 3 or day 1 to 5 (indomethacin 0.2 mg/kg/dose; ibuprofen 10 mg/kg/dose). Control groups received no treatment or normal saline intraperitoneally. Pups were sacrificed at 30 days of age and 6 months of age. Tissue blocks from right kidneys were prepared for light and electron microscopic examination, while total glomerular number was determined in left kidneys using unbiased stereology. Results: Eight pups were included in each group from 14 maternal rats. At 30 days and 6 months there were persistent EM abnormalities of the glomerular basement membrane in those receiving postnatal indomethacin and ibuprofen. There were no significant LM findings at 30 days or 6 months. At 6 months there were significantly fewer glomeruli in those receiving postnatal indomethacin but not ibuprofen (p=0.003) Conclusions: Indomethacin administered during glomerulogenesis appears to reduce the number of glomeruli in adulthood. Alternative options for closing a PDA should be considered including ibuprofen as well as emerging therapies such as paracetamol.