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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics & Gynaecology, Monash Medical Centre, Monash University, Melbourne, Australia.
authors.forename: Stacey J
authors.initials: SJ
authors.lastname: Ellery
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics & Gynaecology, Monash Medical Centre, Monash University, Melbourne, Australia.
authors.forename: Domenic A
authors.initials: DA
authors.lastname: LaRosa
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton Campus, Melbourne, Australia.
authors.forename: Luise A
authors.initials: LA
authors.lastname: Cullen-McEwen
authors.affiliation: Department of Physiology, Monash University, Clayton Campus, Melbourne, Victoria, Australia.
authors.forename: Russell D
authors.initials: RD
authors.lastname: Brown
authors.affiliation: Institute for Physical Activity and Nutrition, Deakin University, Burwood Campus, Melbourne, Australia.
authors.forename: Rod J
authors.initials: RJ
authors.lastname: Snow
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics & Gynaecology, Monash Medical Centre, Monash University, Melbourne, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Walker
authors.affiliation: Department of Physiology, Monash University, Clayton Campus, Melbourne, Victoria, Australia.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Kett
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics & Gynaecology, Monash Medical Centre, Monash University, Melbourne, Australia.
authors.forename: Hayley
authors.initials: H
authors.lastname: Dickinson
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000503:physiopathology*; D024141:Collagen Type IV / Q000378:metabolism; D003401:Creatine / Q000008:administration & dosage / Q000627:therapeutic use*; D019587:Dietary Supplements; D005260:Female; D007668:Kidney / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000517:prevention & control; D007678:Kidney Glomerulus / Q000503:physiopathology; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D009399:Nephrons / Q000503:physiopathology; D009929:Organ Size; D010100:Oxygen / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal
chemical_list: D024141:Collagen Type IV; D003401:Creatine; D010100:Oxygen