In 1988, Brenner et al advanced the hypothesis that the nephron endowment at birth is inversely related to the risk of developing essential hypertension in later life (Am J Hypertens 1:335-347, 1988). This novel perspective on the origins of essential hypertension was taken from the viewpoint that the development and maintenance of hypertension must invoke a renal factor favoring sodium retention, thereby preventing pressure-induced natriuresis from restoring blood pressure toward normal levels. Since nephron numbers in the normal population range from 300,000 to 1,100,000 or more, it was reasoned that a congenital deficit in nephron endowment itself could be the renal risk factor for hypertension: demographic groups in whom hypertension is unusually prevalent tend to have smaller kidneys, implying fewer nephrons, and some inbred hypertensive rat strains have, on average, fewer nephrons than their respective normotensive controls, We argue that recent independent observations in humans relating low birth weight to both increased risk of hypertension in later life and the formation of fewer nephrons at birth lend strong support to the nephron number hypothesis, Moreover, independent experimental studies in rodents suggest that maternal protein intake during gestation is directly related to the numbers of nephrons formed and that when protein intake is restricted, the offspring develop hypertension in maturity, The concept that nephron numbers may be programmed during gestation, as these observations imply, is discussed in relation to the potential advantages and disadvantages of such a mechanism for the next generation; parallels are drawn with the relationship of low birth weight to pancreatic beta cell development and maturity-onset diabetes, We suggest that the programming of fewer nephrons at birth may provide a fitting and overlooked explanation for the eventual development of hypertension in those of low birth weight, especially in cases in which type II diabetes coexists. (C) 1995 by the National Kidney Foundation, Inc.
