Renal dysfunction in early adulthood following birth asphyxia in male spiny mice, and its amelioration by maternal creatine supplementation during pregnancy

Stacey J. Ellery, Domenic A. Larosa, Luise A. Cullen-Mcewen, Russell D. Brown, Rod J. Snow, David W. Walker, Michelle M. Kett, Hayley Dickinson

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5 Citations (Scopus)

Abstract

Background:Acute kidney injury affects ∼70% of asphyxiated newborns, and increases their risk of developing chronic kidney disease later in life. Acute kidney injury is driven by renal oxygen deprivation during asphyxia, thus we hypothesized that creatine administered antenatally would protect the kidney from the long-term effects of birth asphyxia.Methods:Pregnant spiny mice were fed standard chow or chow supplemented with 5% creatine from 20-d gestation (midgestation). One day prior to term (37-d gestation), pups were delivered by caesarean or subjected to intrauterine asphyxia. Litters were allocated to one of two time-points. Kidneys were collected at 1 mo of age to estimate nephron number (stereology). Renal function (excretory profile and glomerular filtration rate) was measured at 3 mo of age, and kidneys then collected for assessment of glomerulosclerosis.Results:Compared with controls, at 1 mo of age male (but not female) birth-asphyxia offspring had 20% fewer nephrons (P < 0.05). At 3 mo of age male birth-asphyxia offspring had 31% lower glomerular filtration rate (P < 0.05) and greater glomerular collagen IV content (P < 0.01). Antenatal creatine prevented these renal injuries arising from birth asphyxia.Conclusion:Maternal creatine supplementation during pregnancy may be an effective prophylactic to prevent birth asphyxia induced acute kidney injury and the emergence of chronic kidney disease.

Original languageEnglish
Pages (from-to)646-653
Number of pages8
JournalPediatric Research
Volume81
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017

Cite this

@article{98ed9e952f7d45adb427d5cf00f1c635,
title = "Renal dysfunction in early adulthood following birth asphyxia in male spiny mice, and its amelioration by maternal creatine supplementation during pregnancy",
abstract = "Background:Acute kidney injury affects ∼70{\%} of asphyxiated newborns, and increases their risk of developing chronic kidney disease later in life. Acute kidney injury is driven by renal oxygen deprivation during asphyxia, thus we hypothesized that creatine administered antenatally would protect the kidney from the long-term effects of birth asphyxia.Methods:Pregnant spiny mice were fed standard chow or chow supplemented with 5{\%} creatine from 20-d gestation (midgestation). One day prior to term (37-d gestation), pups were delivered by caesarean or subjected to intrauterine asphyxia. Litters were allocated to one of two time-points. Kidneys were collected at 1 mo of age to estimate nephron number (stereology). Renal function (excretory profile and glomerular filtration rate) was measured at 3 mo of age, and kidneys then collected for assessment of glomerulosclerosis.Results:Compared with controls, at 1 mo of age male (but not female) birth-asphyxia offspring had 20{\%} fewer nephrons (P < 0.05). At 3 mo of age male birth-asphyxia offspring had 31{\%} lower glomerular filtration rate (P < 0.05) and greater glomerular collagen IV content (P < 0.01). Antenatal creatine prevented these renal injuries arising from birth asphyxia.Conclusion:Maternal creatine supplementation during pregnancy may be an effective prophylactic to prevent birth asphyxia induced acute kidney injury and the emergence of chronic kidney disease.",
author = "Ellery, {Stacey J.} and Larosa, {Domenic A.} and Cullen-Mcewen, {Luise A.} and Brown, {Russell D.} and Snow, {Rod J.} and Walker, {David W.} and Kett, {Michelle M.} and Hayley Dickinson",
year = "2017",
month = "4",
day = "1",
doi = "10.1038/pr.2016.268",
language = "English",
volume = "81",
pages = "646--653",
journal = "Pediatric Research",
issn = "0031-3998",
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number = "4",

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Renal dysfunction in early adulthood following birth asphyxia in male spiny mice, and its amelioration by maternal creatine supplementation during pregnancy. / Ellery, Stacey J.; Larosa, Domenic A.; Cullen-Mcewen, Luise A.; Brown, Russell D.; Snow, Rod J.; Walker, David W.; Kett, Michelle M.; Dickinson, Hayley.

In: Pediatric Research, Vol. 81, No. 4, 01.04.2017, p. 646-653.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Renal dysfunction in early adulthood following birth asphyxia in male spiny mice, and its amelioration by maternal creatine supplementation during pregnancy

AU - Ellery, Stacey J.

AU - Larosa, Domenic A.

AU - Cullen-Mcewen, Luise A.

AU - Brown, Russell D.

AU - Snow, Rod J.

AU - Walker, David W.

AU - Kett, Michelle M.

AU - Dickinson, Hayley

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Background:Acute kidney injury affects ∼70% of asphyxiated newborns, and increases their risk of developing chronic kidney disease later in life. Acute kidney injury is driven by renal oxygen deprivation during asphyxia, thus we hypothesized that creatine administered antenatally would protect the kidney from the long-term effects of birth asphyxia.Methods:Pregnant spiny mice were fed standard chow or chow supplemented with 5% creatine from 20-d gestation (midgestation). One day prior to term (37-d gestation), pups were delivered by caesarean or subjected to intrauterine asphyxia. Litters were allocated to one of two time-points. Kidneys were collected at 1 mo of age to estimate nephron number (stereology). Renal function (excretory profile and glomerular filtration rate) was measured at 3 mo of age, and kidneys then collected for assessment of glomerulosclerosis.Results:Compared with controls, at 1 mo of age male (but not female) birth-asphyxia offspring had 20% fewer nephrons (P < 0.05). At 3 mo of age male birth-asphyxia offspring had 31% lower glomerular filtration rate (P < 0.05) and greater glomerular collagen IV content (P < 0.01). Antenatal creatine prevented these renal injuries arising from birth asphyxia.Conclusion:Maternal creatine supplementation during pregnancy may be an effective prophylactic to prevent birth asphyxia induced acute kidney injury and the emergence of chronic kidney disease.

AB - Background:Acute kidney injury affects ∼70% of asphyxiated newborns, and increases their risk of developing chronic kidney disease later in life. Acute kidney injury is driven by renal oxygen deprivation during asphyxia, thus we hypothesized that creatine administered antenatally would protect the kidney from the long-term effects of birth asphyxia.Methods:Pregnant spiny mice were fed standard chow or chow supplemented with 5% creatine from 20-d gestation (midgestation). One day prior to term (37-d gestation), pups were delivered by caesarean or subjected to intrauterine asphyxia. Litters were allocated to one of two time-points. Kidneys were collected at 1 mo of age to estimate nephron number (stereology). Renal function (excretory profile and glomerular filtration rate) was measured at 3 mo of age, and kidneys then collected for assessment of glomerulosclerosis.Results:Compared with controls, at 1 mo of age male (but not female) birth-asphyxia offspring had 20% fewer nephrons (P < 0.05). At 3 mo of age male birth-asphyxia offspring had 31% lower glomerular filtration rate (P < 0.05) and greater glomerular collagen IV content (P < 0.01). Antenatal creatine prevented these renal injuries arising from birth asphyxia.Conclusion:Maternal creatine supplementation during pregnancy may be an effective prophylactic to prevent birth asphyxia induced acute kidney injury and the emergence of chronic kidney disease.

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U2 - 10.1038/pr.2016.268

DO - 10.1038/pr.2016.268

M3 - Article

VL - 81

SP - 646

EP - 653

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 4

ER -