The pathogenesis of glomerulonephritis (problems and recent understanding)

Abstract

Progress has been made in understanding glomerulonephritis but the answers to many key questions still elude us. It appears that glomerular damage arises from immune events which result from an interaction between a susceptible individual and some environmental agents, usually an infection. In the developed world the role of the genetic constitution is predominant, whilst in the Third World the overwhelming exposure to pathogens may be crucial. Immune complex formation undoubtedly plays a major role in the initiation of glomerular injury, but deposition of soluble preformed complexes within the glomerulus now seems to be only one mechanism, in situ combination of fixed antigen and free antibody, and insoluble (precipitating) complexes both playing a part as well. New understanding of modes of damage to the glomerulus strongly implicates monocytes as injurious agents in both experimental and human nephritis, and platelets may also play a role in amplifying injury. One of the main questions is why only some forms of glomerulonephritis in only some patients progress to renal failure. Whilst continuing exposure to the antigen initiating the nephritis may be important, secondary mechanisms involving autologous antigens may be important. Further, non-immunologic mechanisms which arise from hyperperfusion of glomerular capillaries appear capable of damaging the glomerulus, and both this mechanism and proteinuria itself appear capable of inducing glomerulosclerosis. The role these non-immunologic mechanisms play may be the reason for our failure, in general, to influence the course of glomerulonephritis by manoeuvres designed to inhibit immunologic injury.