The effects of maternal health on fetal kidney development and its function

在澳大利亚土著居民中，肾脏疾病很流行。虽然其中大部分可以通过有效控制A组链球菌皮肤感染来预防，但也有证据表明，对终末期肾病的高易感性与肾脏宫内发育不良有关，因为低出生体重是一个诱发因素。肾功能受损的母亲往往生下体重不足的婴儿。没有关于母体肾功能不全对胎儿肾脏发育的影响的知识。我们最近开发了一种动物模型，可以研究母体肾功能障碍对其后代肾脏发育的影响。人类在最后三个月形成了肾脏中60%的功能单位（肾单位）。绵羊，像人类一样（不像老鼠），在子宫内的生命中完全形成了它们将拥有的所有肾单位。虽然胎儿肾脏在羊水的形成中起着重要作用，但胎儿体液和电解质稳态的调节取决于母体肾功能通过经胎盘转移。如果母体肾功能降低，则胎儿肾脏可能会通过经胎盘平衡暴露于更大的体积和溶质负荷。这可能对肾脏发育产生深远影响，特别是如果再加上母亲饮食不足和母亲盐摄入量高。在这些条件下，我们预测胎儿肾脏的发育将受损，出生后肾功能下降。这意味着肾脏会更快地“老化”。因此，受影响的个人将倾向于在成年后患肾病。在我们的动物模型中，我们将研究母体肾功能不全、胎儿营养不良和母体高盐摄入对胎儿肾脏发育和功能的影响和相互作用。

There is an epidemic of renal disease among Australian aborigines. While much of this could have been prevented by effective control of Group A streptococcal skin infections, there is also evidence that the high susceptibility to end-stage renal disease is related to poor intrauterine development of the kidney as low- birth weight is a predisposing factor. Mothers, whose renal function is impaired, tend to have babies which are low birth weight. There is no knowledge about the effects of maternal renal dysfunction on development of the fetal kidney. We have recently developed an animal model in which we can study the effects of maternal renal dysfunction on the development of the kidney of her offspring. Human beings form 60% of the functional units (nephrons) in the kidney in the last trimester. Sheep, like human beings (and unlike rats), completely form all the nephrons that they will ever have, during intrauterine life. While the fetal kidneys play an essential role in the formation of amniotic fluid, regulation of fetal fluid and electrolyte homeostasis depends on maternal renal function via transplacental transfer. If maternal renal function is reduced, it is likely that the fetal kidneys will be exposed to a greater volume and solute load through transplacental equilibration. This may have a profund effect on renal development especially if coupled with an inadequate maternal diet and a high maternal salt intake. Under these conditions we predict that development of the fetal kidney will be impaired and renal capacity after birth, reduced. This means that the kidney will 'age' more rapidly. Thus the affected individual would be predisposed to renal disease in adult life. In our animal model we will study the effects and interactions of maternal renal insufficiency, poor fetal nutrition and a high maternal salt intake on fetal kidney development and function.