Mackenzie H S, Lawler E V, Brenner B M
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kidney Int Suppl. 1996 Jun;55:S30-4.
In 1988, Brenner, Garcia and Anderson advanced the hypothesis that the nephron endowment at birth is inversely related to the risk of developing essential hypertension in later life. This novel perspective on the origins of essential hypertension was taken from the viewpoint that the development and maintenance of hypertension must involve 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 shortfall 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 counterparts. 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 support to this 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 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.
1988年，布伦纳、加西亚和安德森提出了一个假说，即出生时的肾单位数量与日后患原发性高血压的风险呈负相关。这一关于原发性高血压起源的新观点源自这样一种看法，即高血压的发生和维持必定涉及一个有利于钠潴留的肾脏因素，从而阻止压力性利钠作用使血压恢复至正常水平。由于正常人群中的肾单位数量在30万至110万甚至更多之间，因此有人推断，肾单位数量先天性不足本身可能就是高血压的肾脏危险因素：高血压异常普遍的人群往往肾脏较小，这意味着肾单位数量较少，而且一些近交系高血压大鼠品系平均而言比各自的正常血压对照品系的肾单位数量更少。最近在人类中的独立观察发现，低出生体重与日后患高血压风险增加以及出生时形成的肾单位数量减少都有关联，这支持了这一肾单位数量假说。此外，在啮齿动物中的独立实验研究表明，孕期母体蛋白质摄入量与形成的肾单位数量直接相关，当蛋白质摄入量受到限制时，后代成年后会患高血压。正如这些观察结果所暗示的，肾单位数量可能在孕期就已被编程的这一概念，将结合这种机制对下一代的潜在利弊进行讨论。同时还将低出生体重与胰腺β细胞发育及成年发病型糖尿病的关系进行了类比。我们认为，出生时肾单位数量较少的编程现象可能为低出生体重者最终患高血压提供了一个恰当但被忽视的解释。
