Ellery Stacey J, LaRosa Domenic A, Cullen-McEwen Luise A, Brown Russell D, Snow Rod J, Walker David W, Kett Michelle M, Dickinson Hayley
The Ritchie Centre, Hudson Institute of Medical Research and Department of Obstetrics & Gynaecology, Monash Medical Centre, Monash University, Melbourne, Australia.
Department of Anatomy and Developmental Biology, Monash University, Clayton Campus, Melbourne, Australia.
Pediatr Res. 2017 Apr;81(4):646-653. doi: 10.1038/pr.2016.268. Epub 2016 Dec 20.
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.
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.
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.
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.
急性肾损伤影响约70%的窒息新生儿，并增加其日后患慢性肾病的风险。急性肾损伤是由窒息期间肾脏缺氧驱动的，因此我们推测产前给予肌酸可保护肾脏免受出生窒息的长期影响。
从妊娠20天（妊娠中期）开始，给怀孕的刺毛鼠喂食标准饲料或添加5%肌酸的饲料。在足月前一天（妊娠37天），通过剖腹产分娩幼崽或使其遭受宫内窒息。将幼崽分配到两个时间点之一。在1月龄时收集肾脏以估计肾单位数量（体视学）。在3月龄时测量肾功能（排泄情况和肾小球滤过率），然后收集肾脏以评估肾小球硬化。
与对照组相比，1月龄时，雄性（而非雌性）出生窒息后代的肾单位数量减少20%（P<0.05）。3月龄时，雄性出生窒息后代的肾小球滤过率降低31%（P<0.05），肾小球IV型胶原含量增加（P<0.01）。产前肌酸可预防出生窒息引起的这些肾脏损伤。
孕期补充母体肌酸可能是预防出生窒息所致急性肾损伤和慢性肾病发生的有效预防措施。
