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

Alison L Kent, Mark E Koina, Lina Gubhaju, Luise A Cullen-McEwen, John F Bertram, John Lynnhtun, Bruce Shadbolt, Michael C Falk, Jane E Dahlstrom

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1105 - 1110
Number of pages6
JournalAmerican Journal of Physiology - Renal Physiology
Volume307
Issue number10
DOIs
Publication statusPublished - 2014

Cite this

Kent, Alison L ; Koina, Mark E ; Gubhaju, Lina ; Cullen-McEwen, Luise A ; Bertram, John F ; Lynnhtun, John ; Shadbolt, Bruce ; Falk, Michael C ; Dahlstrom, Jane E. / Indomethacin administered early in the postnatal period results in reduced glomerular number in the adult rat. In: American Journal of Physiology - Renal Physiology. 2014 ; Vol. 307, No. 10. pp. 1105 - 1110.
@article{3c8910b396074282a713277737434856,
title = "Indomethacin administered early in the postnatal period results in reduced glomerular number in the adult rat",
abstract = "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.",
author = "Kent, {Alison L} and Koina, {Mark E} and Lina Gubhaju and Cullen-McEwen, {Luise A} and Bertram, {John F} and John Lynnhtun and Bruce Shadbolt and Falk, {Michael C} and Dahlstrom, {Jane E}",
year = "2014",
doi = "10.1152/ajprenal.00328.2014",
language = "English",
volume = "307",
pages = "1105 -- 1110",
journal = "American Journal of Physiology - Renal Physiology",
issn = "1522-1466",
publisher = "American Physiological Society",
number = "10",

}

Indomethacin administered early in the postnatal period results in reduced glomerular number in the adult rat. / Kent, Alison L; Koina, Mark E; Gubhaju, Lina; Cullen-McEwen, Luise A; Bertram, John F; Lynnhtun, John; Shadbolt, Bruce; Falk, Michael C; Dahlstrom, Jane E.

In: American Journal of Physiology - Renal Physiology, Vol. 307, No. 10, 2014, p. 1105 - 1110.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Indomethacin administered early in the postnatal period results in reduced glomerular number in the adult rat

AU - Kent, Alison L

AU - Koina, Mark E

AU - Gubhaju, Lina

AU - Cullen-McEwen, Luise A

AU - Bertram, John F

AU - Lynnhtun, John

AU - Shadbolt, Bruce

AU - Falk, Michael C

AU - Dahlstrom, Jane E

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://ajprenal.physiology.org/content/307/10/F1105.full-text.pdf+html

U2 - 10.1152/ajprenal.00328.2014

DO - 10.1152/ajprenal.00328.2014

M3 - Article

VL - 307

SP - 1105

EP - 1110

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 1522-1466

IS - 10

ER -