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

BACKGROUND: Acute Kidney Injury (AKI) affects ~70% of asphyxiated newborns, and increases their risk of developing chronic kidney disease (CKD) later in life. AKI 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-days gestation (mid-getstation). One day prior to term (37-days gestation), pups were delivered by caesarean or subjected to intrauterine asphyxia. Litters were allocated to one of two time-points. Kidneys were collected at one month of age to estimate nephron number (stereology). Renal function (excretory profile and GFR) was measured at three months of age, and kidneys then collected for assessment of glomerulosclerosis. RESULTS: Compared to controls, at one month of age male (but not female) birth-asphyxia offspring had 20% fewer nephrons (P<0.05). At three months of age male birth-asphyxia offspring had 31% lower GFR (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 AKI and the emergence of CKD.Pediatric Research (2016); doi:10.1038/pr.2016.268.