Nephron number, hypertension, renal disease, and renal failure
Nephron number, hypertension, renal disease, and renal failure
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DOI：
10.1681/asn.2005020172
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发表时间：
2005-09-01
影响因子：
13.6
通讯作者：
Amann, K
中科院分区：
文献类型：
--
作者：
Hoy, WE;Hughson, MD;Amann, K
原发性高血压是西方世界最常见的疾病之一，影响约26.4%的成年人口，并且正在增加（1）。其原因是异质性的，包括遗传和环境因素（2），但一些观察结果指出肾脏在其发生中的重要作用（3）。除了肾小管转运机制的变化，例如，可能会影响盐的处理，肾脏的结构特征也可能导致高血压。由于人口增长，寿命延长和风险因素的变化，慢性肾脏疾病的负担也在全球范围内增加。虽然单一原因的疾病模型仍然被广泛推广，但多决定因素或“多击”模型，可以适应个人或群体中的多种风险因素，可能更适用（4，5）。不久前，Brenner和他的同事提出，较低的肾单位数量易患原发性高血压和肾脏疾病。他们还提出，高血压和进行性肾功能不全可能是由肾小球肥大和肾小球内高血压引发和加速的，而肾小球肥大和肾小球内高血压是随着肾单位数量减少而发展的（8）。在这篇综述中，我们总结了最近的研究，揭示了这些假设的数据。这些数据为“Barker假说”的可能机制提供了新的解释，该假说认为胎儿宫内发育迟缓易导致日后患慢性疾病（9）。综述描述了肾单位数量的估计方法及其范围、一些决定因素和形态学相关因素。然后考虑肾单位数量减少的可能原因。最后，协会的高血压和肾脏疾病与肾单位数量减少被认为是，并讨论了一些潜在的临床意义。
Essential hypertension is one of the most common diseases in the Western world, affecting about 26.4% of the adult population, and it is increasing (1). Its causes are heterogeneous and include genetic and environmental factors (2), but several observations point to an important role of the kidney in its genesis (3). In addition to variations in tubular transport mechanisms that could, for example, affect salt handling, structural characteristics of the kidney might also contribute to hypertension.The burden of chronic kidney disease is also increasing worldwide, due to population growth, increasing longevity, and changing risk factors. Although single-cause models of disease are still widely promoted, multideterminant or "multihit" models that can accommodate multiple risk factors in an individual or in a population are probably more applicable (4,5). In such a framework, nephron endowment is one potential determinant of disease susceptibility.Some time ago, Brenner and colleagues (6,7) proposed that lower nephron numbers predispose both to essential hypertension and to renal disease. They also proposed that hypertension and progressive renal insufficiency might be initiated and accelerated by glomerular hypertrophy and intraglomerular hypertension that develops as nephron number is reduced (8). In this review, we summarize data from recent studies that shed more light on these hypotheses. The data supply a new twist to possible mechanisms of the "Barker hypothesis," which proposes that intrauterine growth retardation predisposes to chronic disease in later life (9).The review describes how nephron number is estimated and its range and some determinants and morphologic correlates. It then considers possible causes of low nephron numbers. Finally, associations of hypertension and renal disease with reduced nephron numbers are considered, and some potential clinical implications are discussed.