Prenatal programming—effects on blood pressure and renal function

Abstract

Impaired intrauterine nephrogenesis-most clearly illustrated by low nephron number-is frequently associated with low birthweight and has been recognized as a powerful risk factor for renal disease; it increases the risks of low glomerular filtration rate, of more rapid progression of primary kidney disease, and of increased incidence of chronic kidney disease or end-stage renal disease. Another important consequence of impaired nephrogenesis is hypertension, which further amplifies the risk of onset and progression of kidney disease. Hypertension is associated with low nephron numbers in white individuals, but the association is not universal and is not seen in individuals of African origin. The derangement of intrauterine kidney development is an example of a more general principle that illustrates the paradigm of plasticity during development-that is, that transcription of the genetic code is modified by epigenetic factors (as has increasingly been documented). This Review outlines the concept of prenatal programming and, in particular, describes its role in kidney disease and hypertension.

The diabetic pregnancy and offspring blood pressure in childhood: a systematic review and meta-analysis

“…Low nephron number is a powerful predictor of adult hypertension [53,54], and adults with primary hypertension have fewer nephrons than normotensive controls [55]. Nephron count is 13-22% lower in rats born to diabetic mothers [56].…”

Effect of intrauterine growth retardation on liver and long-term metabolic risk

“…14 Another example of permanent alteration induced by developmental plasticity is provided by the observation that adult nephron numbers are reduced both in humans and in animals exposed to suboptimal uterine environment that develop hypertension in adult life. [15][16][17][18] This might represent the consequence of a biological trade-off to spare energy in response to in utero nutrient deprivation, having immediate but no long-term adaptive value.…”

2011 Homer Smith Award

“…[73][74][75] Epidemiologic and morphologic studies of nephron number in autopsy material from individuals of different ages and ethnic backgrounds suggest this is also the case in humans. 66,[73][74][75][76] The finding that ouabain, belonging to the family of CTSs, rescues the development of fetal kidneys exposed to malnutrition may open a new avenue for protection against adverse developmental programming of the kidney and eliminate one risk factor for progressive renal disease.…”