The Toxic-Allergic Hypothesis

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According to this hypothesis the first and causal event in glomerulonephritis is not an infection or an immunological reaction in the glomeruli, but an exposure to nephrotoxic  chemicals, either by inhalation, by skin contact or by ingestion. The precise mechanism by which the chemicals produce renal damage is still uncertain, but the primary targets are most probably the tubular cells and/or the cells of the immune system. The deposition of immunoglobulins and complement in the glomeruli is a secondary phenomenon with little importance for glomerular function or structure (Ravnskov 1985, Ravnskov 1988, Ravnskov 1989, Ravnskov 1998, Ravnskov 1999).

The tubular cells have many important functions in the body. They regulate the balance of salt and water in the blood, they maintain the body’s acid/base balance, they prevent important substances from being lost in the urine after having been filtered out through the glomerular filters, and many toxic substances are taken up from the blood and secreted into the urine by these cells. The latter function is probably crucial for the start of glomerulonephritis because if too much of a toxic chemical has come into the blood, its accumulation in the tubular cell may damage and even kill the cell. The damage of the tubular cells may lead to inflammation and scarring of the interstitium. These changes lead to shrinkage of the renal tissue, the tubules become narrow,the urine flow is retarded, and gradually renal function goes down.

Another possibility is that white blood cells react with the chemical and starts an allergic reaction. Also this reaction may lead to inflammation in the interstitium. White blood cells may become stimulated by the allergic reaction to produce lymfokines, small molecules that may damage the epithelial cells of the GBM resulting in an increased permeability to plasma proteins and facilitate the deposition of macromolecules, for instance antibodies and complement factors, in the glomeruli. Such damage may even be produced directly by the toxic chemicals. Most probably all mechanisms operate together. 

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