Glomerulonephritis is a general term for a group of disorders in which:
• There is immunologically mediated injury to glomeruli.
• The kidneys are involved symmetrically.
• Secondary mechanisms of glomerular injury come into play following an initial immune insult.
• The renal lesion may be part of a generalized disease, e.g. systemic lupus erythematosus (SLE).
Two chief pathogenetic mechanisms are recognized:
1 Deposition or in situ formation of immune complexes (most human glomerulonephritides)
2 Deposition of antiglomerular basement membrane antibody (less than 5% of glomerulonephritides)
Both of these pathogenetic mechanisms activate secondary mechanisms that produce glomerular damage.
Immune complex nephritis
Circulating antigen-antibody complexes are deposited in the kidney or complexes are formed locally when circulating free antigen has become trapped in the glomerulus. The nature of the antigen involved in the complex formation is important in many instances. The antigen may be:
EXOGENOUS (e.g. bacterial). For example, a nephritogenic Lancefield group A f3-haemolytic Streptococcus can cause glomerulonephritis in previously healthy individuals.
ENDOGENOUS. For example, patients with SLE may form antibodies to host DNA, leading to a glomerulonephritis.
Harmful immune complexes can also occur when there is impaired host ability to produce appropriate antibody. Certain strains of black mice regularly develop glomerulonephritis as a result of an impaired ability to produce antibody of appropriate quality or quantity, and it is likely that there are human counterparts of this phenomenon. There is an association between HLA markers and certain nephritides.
Impaired ability on the part of the host to clear immune complexes from the circulation and deficiencies in the complement system are each associated with an increased incidence of glomerulonephritis.
Antiglomerular basement membrane (anti-GBM) antibody
Anti-GBM antibody reacts with an antigen in the glomerular basement membrane, producing a rare form of glomerular damage. It is of the IgG type. The antibody can also react with alveolar capillary basement membrane (owing to shared antigens) and can cause both lung haemorrhage and glomerulonephritis (Goodpasture’s syndrome).
Secondary mechanisms of glomerular injury Several events can be triggered by the above immunological insults:
• Complement activation
• Fibrin deposition
• Platelet aggregation
• Inflammation with neutrophil-dependent mechanisms
• Activation of kinin systems
Immune complex or anti-GBM antibody deposition trigger these mechanisms to varying degrees, resulting in an increase in capillary permeability and glomerular damage. In experimentally induced glomerulonephritis in animals, prior anticoagulation, prevention of complement activation, and depletion of polymorphonuclear leucocytes have all been shown to reduce the severity of the induced glomerular injury. However, in humans presenting with most forms of glomerulonephritis these measures do not help.
T-cell dysfunction may play a part in the production of lesions when immune complexes are not seen.
In the majority of patients with immune complexmediated glomerulonephritis, the cause is unknown, i.e. the nature of the antigen involved is not determined. Antigen derived from viruses, bacteria, parasites, drugs and from the host may be involved. The reasons for the development of anti-G BM antibody are not known; viral or solvent damage to alveolar capillary basement membrane, rendering it antigenic, has been suggested as a possible cause.