Luyckx Valerie A, Brenner Barry M
Renal Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Kidney Int Suppl. 2005 Aug(97):S68-77. doi: 10.1111/j.1523-1755.2005.09712.x.
More and more evidence is emerging that highlights the far-reaching consequences of prenatal (intrauterine) programming on organ function and adult disease. In humans, low birth weight (LBW) occurs more frequently in disadvantaged communities among whom there is often a disproportionately high incidence of adult cardiovascular disease, hypertension, diabetes mellitus, and kidney disease. Indeed, many epidemiologic studies have found an inverse association between LBW and higher blood pressures in infancy and childhood, and overt hypertension in adulthood. Multiple animal models have demonstrated the association of LBW with later hypertension, mediated, at least in part, by an associated congenital nephron deficit. Although no direct correlation has been shown between nephron number and birth weight in humans with hypertension, nephron numbers were found to be lower in adults with essential hypertension, and glomeruli tend to be larger in humans of lower birth weight. An increase in glomerular size is consistent with hyperfiltration necessitated by a reduction in total filtration surface area, which suggests a congenital nephron deficit. Hyperfiltration manifests clinically as microalbuminuria and accelerated loss of renal function, the prevalence of which are higher among adults who had been of LBW. A kidney with a reduced nephron number has less renal reserve to adapt to dietary excesses or to compensate for renal injury, as is highlighted in the setting of renal transplantation, where smaller kidney to recipient body-weight ratios are associated with poorer outcomes, independent of immunologic factors. Both hypertension and diabetes are leading causes of end-stage renal disease worldwide, and their incidences are increasing, especially in underdeveloped communities. Perinatal programming of these 2 diseases, as well as of nephron number, may therefore have a synergistic impact on the development of hypertension and kidney disease in later life. Existing evidence suggests that birth weight should be used as a surrogate marker for future risk of adult disease. Although the ideal solution to minimize morbidity would be to eradicate LBW, until this panacea is realized, it is imperative to raise awareness of its prognostic implications and to focus special attention toward early modification of risk factors for cardiovascular and renal disease in individuals of LBW.
越来越多的证据表明，产前（子宫内）编程对器官功能和成人疾病具有深远影响。在人类中，低出生体重（LBW）在弱势社区更为常见，这些社区中成人心血管疾病、高血压、糖尿病和肾脏疾病的发病率往往过高。事实上，许多流行病学研究发现，低出生体重与婴儿期和儿童期较高的血压以及成年期明显的高血压之间存在负相关。多种动物模型已经证明低出生体重与后期高血压有关，至少部分是由相关的先天性肾单位缺陷介导的。虽然在患有高血压的人类中，肾单位数量与出生体重之间没有直接相关性，但在原发性高血压成人中发现肾单位数量较低，而低出生体重的人肾小球往往较大。肾小球大小的增加与总滤过表面积减少所必需的超滤一致，这表明存在先天性肾单位缺陷。超滤在临床上表现为微量白蛋白尿和肾功能加速丧失，在低出生体重的成年人中其患病率更高。肾单位数量减少的肾脏适应饮食过量或补偿肾损伤的肾储备较少，这在肾移植的情况下得到了突出体现，即较小的肾脏与受体体重比与较差的结果相关，与免疫因素无关。高血压和糖尿病都是全球终末期肾病的主要原因，而且它们的发病率正在上升，特别是在不发达社区。因此，这两种疾病以及肾单位数量的围产期编程可能对晚年高血压和肾脏疾病的发展产生协同影响。现有证据表明，出生体重应作为未来成人疾病风险的替代指标。虽然将发病率降至最低的理想解决方案是消除低出生体重，但在实现这一万灵药之前，必须提高对其预后影响的认识，并特别关注对低出生体重个体心血管和肾脏疾病风险因素的早期干预。
