English

Abstract

Introduction Glomerulonephritis is seen as a serious immunologic disease of the glomeruli. However, permanent renal damage has never been produced experimentally by immunisation without the concomitant use of Freund’s adjuvant or other tubulotoxic chemicals. Also contradictory is that renal failure is strongly associated with the degree of tubulointerstitial damage, both in experimental and human glomerulonephritis, whereas weak or no association at all has been found with the degree of glomerular damage. There is solid clinical and experimental evidence that the exposure to tubulotoxic chemicals alone is able to produce glomerulonephritis and renal failure, and there is increasing evidence that such exposure is a major cause of renal failure in other kidney diseases. The aim of this review was to discuss the role of tubulotoxic chemicals in renal failure. Conclusion As several studies have observed improvement of renal function after cessation of hydrocarbon exposure, it is reasonable to expect that avoiding other types of toxic exposure may be beneficial as well. It should therefore be mandatory to ask all the patients with renal failure about possible exposure to tubulotoxic chemicals, preferably by experienced occupational hygienists, and to support attempts to avoid such exposure. Introduction Glomerulonephritis (GN) is an innocent disease as long as renal function is normal. To prevent or to treat serious GN it is therefore necessary to know what causes renal failure. For many years, the interest has been focused on various immunological reactions, either between foreign antigens that arrive into the glomeruli after having reacted with circulating antibodies and complement; or between autologous anti-kidney antibodies and various kidney cells or membranes. In addition severe proteinuria has been considered noxious for the tubular cells. However, there are a host of contradictory observations. This review discusses the crucial role of tubulotoxic chemicals in renal failure. Discussion The author has referenced some of his own studies in this review. These referenced studies have been conducted in accordance with the Declaration of Helsinki (1964) and the protocols of these studies have been approved by the relevant ethics committees related to the institution in which they were performed. All human subjects, in these referenced studies, gave informed consent to participate in the studies. The role of the immunological processes If the immunological reactions in the glomeruli are the cause of renal failure, directly or indirectly, there should exist an association between the number of glomerular immune complexes (ICs) or the degree of glomerular damage, and renal function, but it is not so. Greater amount of glomerular ICs are often seen in sheep, steers, guinea pigs, horses, mice and rabbits with normal renal function and normal urine1. Patients with malignancies, alcoholic liver disease and essential hypertension may have such deposits as well, although their renal function and their urine are normal1. A single injection of a foreign antigen into experimental animals results in the production of circulating and glomerular ICs, but unless the animals are injected with Freund’s adjuvant (FA) as well, or unless the foreign antigen is injected repeatedly, no renal damage is seen apart from mild and transient proteinuria1,2. In accordance, most cases of human GN following an acute infection may heal without permanent damage of the kidneys, but renal failure may be seen in patients with chronic infections, or if the patients are exposed to tubulotoxic chemicals. Experimental GN can also be produced in rats by autologous antibrush border or anti-podocyte antibodies, either by immunisation with rat kidney cells (active Heymann nephritis), or by injecting rabbit antirat brush border antibodies into rats (passive Heymann nephritis). These models are used as an argument for the idea that serious GN is caused by immunologic mechanisms. However, without FA autologous anti-kidney antibodies do not produce more than mild and transient proteinuria. In passive Heymann nephritis injected heterologous rabbit antibodies bind to the glomerulus immediately, but no harm is produced until a few days later, when the autologous anti-rabbit Ig antibodies lead to complex formation in situ1,2. However, this model cannot be used as an argument for an immunologic mechanism, as the presence of heterologous antibodies is most unlikely in human GN. * Corresponding author Email: ravnskov@tele2.se Magle Stora Kyrkogata 9, S 22350 Lund, Sweden