Progressive Crescentic Glomerulonephritis



Rapidly progressive glomerulonephritis (RPGN) describes a nephritic syndrome that is more common after the third decade of life, has a clinical presentation similar to that of postin­fectious AGN, and is characterized by extensive glomerular crescent formation. The major clinical distinction is that RPGN displays a rapid pro­gression (less than six months) to end-stage renal failure. Serum complement levels are normal, a fact that helps in the early distinction of this syn­drome from postinfectious or SLE glomerulo­nephritis.

Two categories of RPGN have been identified, based on the distinctive histopathology and serology of each variety. Antiglomerular basement membrane (anti-GBM) glomerulonephritis is di­agnosed by the identification of circulating anti-GBM antibodies. Goodpasture’s syndrome is a form of anti-GBM nephritis in which pulmonary hemorrhage is a major feature of the clinical dis­ease. Idiopathic RPGN has a similar renal course but lacks circulating antiGBM antibody.

Light microscopy of all forms of RPGN is dom­inated by the appearance of extensive glomerular crescents in more than 50 per cent of glomeruli. These cellular crescents represent both prolifer­ating urinary epithelial cells and invading tissue macrophages. Crescents are also seen in severe forms of other types of glomerulonephritis, in­cluding post-streptococcal and anaphylactoid purpura.
Anti-GBM disease is identified by continuous, linear staining for IgG and C3 along the basement membranes of glomerular capillaries . Linear immune staining alone, however, is not pathognomonic and has been seen in diabetic ne­phropathy and lupus glomerulonephritis. In Goodpasture’s syndrome, linear staining of pul­monary capillary basement membranes can also be demonstrated. Idiopathic RPGN has variable immune staining that ranges from patchy, seg­mental staining for C3 and IgM to cases in which no immunofluorescence is seen. Electron micros­copy does not regularly show deposits in either form of this disorder, but breaks in the glomerular basement membrane are common.

Treatment in anti-GBM nephritis is directed to­ward lowering the level of circulating anti-GBM antibody. Plasmapheresis to remove circulating antibody, in combination with corticosteroids and immunosuppressive drugs to reduce antibody production, has been successful in halting pro­gression of disease in some patients. Individuals with an initial serum creatinine greater than 5 mg/ dl or those having crescents in more than 80 per cent of glomeruli on renal biopsy are not likely to respond to treatment. Anti-GBM disease has been shown to recur in transplanted kidneys. No ther­apy has been shown to be of consistent benefit in the treatment of idiopathic RPGN.