Immunopathologic studies over the past two decades have demonstrated that rapidly progressive
glomerulonephritis (RPGN) can result from glomerular deposition of
anti-GBM antibody,
immune complexes, or from some as yet undefined mechanism that does not involve glomerular antibody deposition. The latter process may be cell mediated and resembles a small vessel
vasculitis. Most cases of idiopathic RPGN are not accompanied by pathogenic glomerular
immunoglobulin deposition. Recent experimental studies of immune mechanisms of glomerular injury have identified several new processes that can induce damage to the capillary wall sufficient to result in crescentic
glomerulonephritis (GN). These include direct effects of
anti-GBM antibody alone and of the
complement C5b-9 (
membrane attack) complex, nephritogenic effects of inflammatory effector cells that involve
reactive oxygen species and glomerular halogenation, and injury mediated by sensitized lymphocytes independently of antibody deposition. Macrophages have been shown to participate in both intracapillary and extracapillary
fibrin deposition and crescent formation as well as to mediate capillary wall damage. The role of resident glomerular cells and cell-cell interactions in
glomerulonephritis is still under active investigation. Despite these several advances in understanding immune injury to the glomerulus,
therapy for RPGN remains largely empiric. Although the prognosis in RPGN has clearly improved over time, no form of disease-specific
therapy has been clearly shown yet to be beneficial in a controlled study. Interpretation of the existing literature on
therapy is complicated by the availability of only historical rather than concurrent controls, lack of attention to several variables known to affect disease outcome, and uncertainty regarding bias in favor of reporting positive results. Available data suggests that optimal outcomes may be achieved in
anti-GBM nephritis by treatment with
steroids, immunosuppression and
plasma exchange, particularly when
therapy is directed at patients with mild but rapidly progressive disease before
oliguria or severe
azotemia develop. Pulse
steroids are probably the most cost-effective
therapy for the idiopathic form of RPGN, but treatment with
cytotoxic agents should be considered if clinical or histologic evidence of
vasculitis is present.