Does undernutrition during development program renal glomerular injury and hypertension? -From animal studies to patients

在发达国家，低出生体重(LBW)婴儿的数量有所增加。此外，发育过程中的不良事件增加了日后罹患心血管和肾脏疾病的风险。为了确定发育期间营养减少是否导致局灶性节段性肾小球剥离(FSGS)，我们从一个禽类模型到经肾活检诊断的儿童进行了翻译研究。孵化前提取蛋清5-10%的日本鸣禽体重低于对照组。EwWbird的孵化率也降低了，肾小球变小了。此外，围产期雏鸡血浆糖皮质激素水平和肾小球细胞凋亡率较高，导致成年后肾小球数量减少。在成熟的蛋鸡肾小球足细胞中，细胞间黏附分子和裂隙横隔膜保持良好，而毛细血管环呈局灶性膨胀；层粘连蛋白阳性物质聚集在系膜。自1990年以来在新泻大学进行的肾活检(n=206)中，33%(33%)的儿童被诊断为FSGS(n=15)。LBW-FSGS患儿肾小球硬化性病变明显多于正常BW-FSGS患儿，足细胞数低于正常BW-FSGS患儿。受损或不完全成熟的系膜提供的结构支持减少，并可能引发肾硬化症。动物实验结果与临床观察结果一致。LBW可能被认为是FSGS的一个风险因素。

In advanced countries, the number of low birth weight (LBW) babies increased. Moreover, adverse events during development increase vulnerability tocardiovascular and renal disease in later life. To determine whether reduced nutrition duringdevelopment leads to focal segmental glomeruloscleorsis (FSGS), we conducted translationalresearch from an avian model to children diagnosed by renal biopsies. Japanese quail in which5-10% egg white was withdrawn (EwW) before incubation had lower BW than controls. EwWbirds also had a reduced hatching rate and smaller glomeruli. Furthermore, plasmaglucocorticoid levels and glomerular apoptosis were higher in perinatal EwW quail, leading tothe decrease in number of glomeruli in adult. In glomerular podocytes from mature EwW quail,intercellular adhesion molecules and slit diaphragms were well maintained, whereas capillaryloops showed focal ballooning; laminin-positive substance was accumulated in the mesangium.Thirty-three percent (33%) of chidren diagnosed by renal biopsies (n = 206) conducted atNiigata University since 1990 as having FSGS (n = 15) had LBW. The LBW-FSGS childrenshowed glomeruli with sclerotic lesions significantly more than normal BW-FSGS children, andthe number of podocytes was lower. Damaged or incompletely mature mesangium providesreduced architectural support and may trigger the nephrosclerosis. The results from the animalexperiments agree with the clinical observations. LBW may be deemed a risk factor for FSGS.