Greive K A, Nikolic-Paterson D J, Guimarães M A, Nikolovski J, Pratt L M, Mu W, Atkins R C, Comper W D
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Am J Pathol. 2001 Sep;159(3):1159-70. doi: 10.1016/S0002-9440(10)61792-0.
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 approximately -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 the 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. This 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 the glomerular basement membrane. It is also apparent that approaches to glomerular pathology and proteinuria as risk factors in renal disease must be reassessed.
长期以来，肾病状态下白蛋白分数清除率的增加一直被归因于肾小球滤过屏障功能障碍。本研究使用放射性标记的大鼠血清白蛋白、转铁蛋白、IgG和多分散性菲可，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小球肾炎中体内分数清除率的变化。在对照大鼠中，通过证明羧甲基菲可（价态约为-39）与不带电荷的菲可具有相同的分数清除率，证实了电荷选择性的缺乏。两种疾病对分数清除率测量表现出相似的影响，提示存在潜在的共同机制。在疾病状态下，通过放射性测定的蛋白质分数清除率与通过放射免疫测定法测定的结果之间具有良好的一致性。与对照组相比，疾病状态下IgG的分数清除率有轻微增加，这与等效大小菲可的变化情况相似，提示这种增加是由于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，与白蛋白等效大小的菲可的分数清除率均未增加，而通过放射性测定白蛋白的分数清除率增加了12至14倍，通过放射免疫测定法测定则增加了4500至6600倍。本研究表明，肾小球肾炎并非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处理的改变所致。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研究方法。
