Glomerular permselectivity factors are not responsible for the increase in fractional clearance of albumin in rat glomerulonephritis

Glomerular permselectivity factors are not responsible for the increase in fractional clearance of albumin in rat glomerulonephritis
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DOI:
10.1016/s0002-9440(10)61792-0
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发表时间:
2001-09-01
影响因子:
6
通讯作者:
Comper, WD
Comper, WD
中科院分区:
医学2区
文献类型:
--
作者:
Greive, KA;Nikolic-Paterson, DJ;Comper, WD

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肾病状态下白蛋白清除率增加长期以来一直被归因于肾小球选择性通透性功​​能障碍。本研究使用放射性标记的大鼠血清白蛋白、转铁蛋白、IgG和多分散聚蔗糖,研究了它们在嘌呤霉素氨基核苷肾病和抗肾小球基底膜肾炎中体内清除分数的变化。在对照大鼠中,通过证明羧甲基聚蔗糖(化合价类似于-39)与不带电的聚蔗糖具有相同的清除率分数,证实了电荷选择性的缺乏。两种疾病对清除率测量值表现出相似的影响,表明潜在的共同机制。在疾病中,通过放射性测定的蛋白质清除率与通过放射免疫测定法测定的蛋白质清除率之间存在良好的一致性。与对照相比,疾病中 IgG 的清除分数小幅增加是明显的,这反映了等效尺寸 Ficoll 的变化,表明死亡增加是因为肾小球毛细血管壁中一小部分大孔的形成。然而,在这两种疾病中,与白蛋白相当大小的聚蔗糖的清除率分数没有增加,但根据放射性测定,白蛋白的清除率分数增加了12至14倍,根据放射免疫测定法测定,增加了4500至6600倍。 Ibis 研究表明,肾小球肾炎不是一种与肾小球对白蛋白通透性变化相关的疾病,而是由于肾小球基底膜远端细胞对白蛋白的处理发生了变化。同样明显的是,必须重新评估将肾小球病理学和蛋白尿作为肾脏疾病危险因素的方法。
The increased fractional clearance of albumin in nephrotic states has long been attributed to glomerular permselectivity dysfunction. Using radiolabeled rat serum albumin, transferrin, IgG, and polydisperse Ficoll, this study investigated the changes in their in vivo fractional clearance in puromycin aminonucleoside nephrosis and anti-glomerular basement membrane glomerulonephritis. in control rats the lack of charge selectivity was confirmed by the demonstration that carboxymethyl Ficoll (valence similar to -39) had the same fractional clearance as uncharged Ficoll. Both diseases exhibited similar effects on fractional clearance measurements suggesting an underlying common mechanism. in disease, there was good agreement between the fractional clearance of proteins determined by radioactivity as compared to those determined by radioimmunoassay. A small increase in the fractional clearance for IgG was evident in disease as compared to controls, which mirrored the change in the equivalent size Ficoll, suggesting that die increase is because of the development of a small proportion of large pores in the glomerular capillary wall. There was no increase, however, in the fractional clearance of Ficoll of equivalent size to albumin in either disease, yet the fractional clearance of the albumin increased by 12 to 14 times as determined by radioactivity and 4500 to 6600 times as determined by radioimmunoassay. Ibis study demonstrates that glomerulonephritis is not a disease associated with changes in glomerular permeability to albumin but is because of alterations in albumin processing by cells distal to die glomerular basement membrane. It is also apparent that approaches to glomerular pathology and proteinuria as risk factors in renal disease must be reassessed.