Prenatal causes of kidney disease.

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.