Koleganova N, Piecha G, Ritz E
Ruperto Carola University Heidelberg, Heidelberg, Germany.
Blood Purif. 2009;27(1):48-52. doi: 10.1159/000167008. Epub 2009 Jan 23.
It has recently been increasingly recognised that disturbed intra-uterine development may impact on renal and cardiovascular risk in adult life, e.g. albuminuria and chronic kidney disease, hypertension, type 2 diabetes or cardiovascular events. According to Barker's hypothesis, when resources in utero are restricted, their allocation to the development of the kidney and pancreatic islets is restricted to guarantee appropriate development of the brain and heart. The underlying epigenetic mechanisms involve modification of gene expression by altered DNA methylation and histone acetylation as well as by allocation of stem cells. The result of this trade-off between the brain and kidney during organogenesis is a diminished number of nephrons ('nephron underdosing') which predisposes to albuminuria and risk of chronic kidney disease, as well as hypertension. In parallel, changed appetite centres, insulin resistance and beta-cell development predispose to obesity, metabolic syndrome and type 2 diabetes and the resulting renal sequelae. Numerous factors may trigger intra-uterine restriction of fetal growth, such as uterine underperfusion, maternal malnutrition, hyperglycaemia and hyperinsulinaemia of the mother, smoking or medications.
最近人们越来越认识到，子宫内发育紊乱可能会影响成年后的肾脏和心血管疾病风险，例如蛋白尿和慢性肾病、高血压、2型糖尿病或心血管事件。根据巴克假说，当子宫内资源受限，这些资源对肾脏和胰岛发育的分配就会受限，以确保大脑和心脏的正常发育。潜在的表观遗传机制包括通过改变DNA甲基化和组蛋白乙酰化以及干细胞分配来修饰基因表达。在器官发生过程中，大脑和肾脏之间这种权衡的结果是肾单位数量减少（“肾单位剂量不足”），这易导致蛋白尿和慢性肾病风险以及高血压。同时，食欲中枢改变、胰岛素抵抗和β细胞发育会导致肥胖、代谢综合征和2型糖尿病以及由此产生的肾脏后遗症。许多因素可能引发胎儿生长的子宫内受限，如子宫灌注不足、母亲营养不良、母亲高血糖和高胰岛素血症、吸烟或药物。
