Non-systemic glomerulonephritis: exposure to nephro- and immunotoxic chemicals predispose to immunologic harassment

Glomerulonephritis is thought to be caused by immune complexes trapped or formed in the glomeruli. But immune complexes are found in the glomeruli of many normal mammals and of patients with non-renal diseases, and immune complexes trapped or formed experimentally in the glomeruli induce mild proteinuria at most suggesting that additional factors must be responsible. An induction of serious renal damage in experimental glomerulonephritis demands a chronic supply of antigen, rarely seen in human glomerulonephritis; or the use of heterologous antibodies, a design with questionable clinical relevance; or immuno- and nephrotoxic chemicals; or Freund's adjuvant which is also nephrotoxic. It is therefore suggested that the pathogenesis of human non- systemic glomerulonephritis includes exposure to nephro- and immunotoxic chemicals, the deposition of glomerular immune complexes being secondary. The hypothesis has clinical support: a majority of patients have been exposed to such chemicals, mainly hydrocarbons; and the tubulointerstitial changes in glomerulonephritis are better correlated to renal function and clinical course than are the glomerular changes. The chemicals enhance or derange immunizations and sensitize the kidneys to immunological reactions.