Ravnskov U
Scand J Immunol. 1998 Nov;48(5):469-74.
Membranous glomerulonephritis (MGN) is said to be caused by circulating autoantibodies against antigen(s) located to the epithelial side of the glomerular capillaries. Membranous glomerulonephritis with severe renal damage can be produced experimentally by injections of heterologous antibodies, but this model is obviously of questionable relevance. It can also be produced by immunizing the animal with antigen mixed with Freund's adjuvant, but this model does not prove that the damage is exerted by antibodies because Freund's adjuvant is nephrotoxic and is itself able to produce MGN. It has not yet been demonstrated experimentally that autologous antibodies alone can produce more than trace or transient proteinuria; and kidney biopsies in unselected humans have shown that MGN is a frequent finding in individuals with normal urine and normal renal function, indicating that a subepithelial formation of immune complexes is also harmless to humans. Severe glomerulonephritis without immune complex formation can easily be produced experimentally with many nephrotoxic chemicals. It is therefore suggested that the primary event in MGN, and probably other subgroups, is a toxic or allergic tubulointerstitial reaction to chemicals or drugs and that the formation of glomerular immune complexes is a later and secondary phenomenon. In agreement, renal function and the course in MGN and other glomerulonephritides are strongly correlated with the degree of tubulointerstitial damage, but totally unrelated to the degree of glomerular damage. The hypothesis explains why a large number of patients with endstage renal failure owing to glomerulonephritis have been heavily exposed to environmental pollutants.
膜性肾小球肾炎（MGN）据说是由针对位于肾小球毛细血管上皮侧抗原的循环自身抗体引起的。通过注射异种抗体可实验性地产生伴有严重肾损伤的膜性肾小球肾炎，但该模型的相关性显然存疑。也可通过用与弗氏佐剂混合的抗原免疫动物来产生，但该模型并不能证明损伤是由抗体所致，因为弗氏佐剂具有肾毒性，自身就能导致膜性肾小球肾炎。目前尚未通过实验证明自体抗体 alone 能产生超过微量或短暂性蛋白尿的情况；对未经过挑选的人类进行肾活检显示，膜性肾小球肾炎在尿液正常且肾功能正常的个体中很常见，这表明上皮下免疫复合物的形成对人类也是无害的。使用多种肾毒性化学物质可很容易地在实验中产生无免疫复合物形成的严重肾小球肾炎。因此有人提出，膜性肾小球肾炎以及可能其他亚组中的主要事件是对化学物质或药物的毒性或过敏性肾小管间质反应，而肾小球免疫复合物的形成是后期的继发现象。与此一致的是，膜性肾小球肾炎和其他肾小球肾炎的肾功能及病程与肾小管间质损伤程度密切相关，但与肾小球损伤程度完全无关。该假说解释了为何大量因肾小球肾炎导致终末期肾衰竭的患者曾大量接触环境污染物。
