title: Maternal nutrition, low nephron number, and hypertension in later life: pathways of nutritional programming.
abstract: A large body of epidemiologic literature supports an inverse relation between birth weight and both systolic blood pressure and prevalence of hypertension, but mechanisms through which lower birth weight increases risk for hypertension are not established. This article advances the view that 1) permanently reduced nephron number is essential but not alone sufficient to mediate nutritionally induced hypertension; and 2) fetally programmed propensity for increased appetite and accelerated postnatal growth, thus generating inappropriately increased body mass, is a necessary "second hit" to actualize hypertension vulnerability. Based on decades of nephrologic research, this increased ratio of body mass (excretory load) to nephron number (excretory capacity) induces intrarenal compensations (tubular and glomerular hypertrophy with single-nephron hyperfiltration and intrarenal renin-angiotensin II activation), which maintain normal glomerular filtration rate at the expense of systemic and glomerular hypertension and at the risk of progressive renal disease. The vigor of the intrarenal compensatory responses is markedly greater in the immature than in the mature kidney, potentially explaining the greater risk of nephron deficits being present early in life as compared with the minimal risk in adult kidney donors. Effective interventions have not yet been defined. Suboptimal maternal nutrition, pervasive in both developed and developing countries, offers a window of opportunity to enhance the cardiovascular and renal health of future generations.
authors: OHSU Heart Research Center and Division of Nephrology and Hypertension, Department of Medicine and Research Service, Oregon Health and Science University and Portland Veterans Administration Medical Center, Portland, OR 97239, USA. bagbys@ohsu.edu
authors: Susan P
authors: SP
authors: Bagby
mesh_terms: D005260:Female; D047109:Fetal Development / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D007231:Infant, Newborn; D007668:Kidney / Q000033:anatomy & histology*; D039382:Maternal Nutritional Physiological Phenomena; D008954:Models, Biological; D009399:Nephrons; D012307:Risk Factors