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RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS


RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS
Rapidly progressive glomerulonephritis (RPGN) is a severe form of glomerulonephritis (GN) in which there is rapid loss of renal function over the course of weeks to months. Other findings are also typical of the nephritic syndrome (see Plate 4-14), including hematuria with dysmorphic red blood cells and red blood cell casts, proteinuria, oliguria, and hypertension.

RPGN is not a singular process with a unique pathophysiology; rather, it is a pattern of severe glomerular inflammation that may occur secondary to any kind of glomerulonephritis. In all cases, RPGN invariably features the histologic finding of cellular crescents. These occur when the glomerular inflammation is severe enough to cause compromise of the basement mem- brane, with resultant rupture of the glomerular capillary walls and leakage of inflammatory cells into Bowman’s space. The crescent-shaped cellular aggregates that form along the parietal lining of Bowman’s capsule consist of extravasated leukocytes, epithelial cells, and eventually myofibroblasts. The presence of crescents is the cardinal pathologic finding of RPGN, which is thus often called crescentic GN.
RPGN can occur secondary to immune complex GN, pauci-immune GN, and antiglomerular basement membrane (anti-GBM) disease (see Plate 4-14 for more details on each). These diagnostic categories are istinguished based on immunofluorescence findings.

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

IMMUNE COMPLEX DISEASE
Immune complex (IC) GN encompasses a large group of diseases that, in a small number of cases, are severe enough to cause RPGN. Because ICGN is so much more common than pauci-immune or anti-GBM disease, however, it accounts for approximately 25% of total RPGN cases. Any form of immune complex GN can present as RPGN, although the most common culprits are lupus nephritis (see Plate 4-49), Henoch-Schönlein purpura (see Plate 4-61), IgA nephropathy (see Plate 4-16), and postinfectious GN (see Plate 4-19).
A characteristic finding of immune complex RPGN is granular immunofluorescent staining of the mesangium or capillary wall for antibodies and complement components. When ICGN causes crescent formation, usually a smaller fraction of glomeruli (25%) are affected when compared with pauci-immune or anti-GBM disease (50%). The management of ICGN, in general, varies according to the underlying disease process. The presence of crescents, however, warrants aggressive treatment with steroids and, in many cases, cytotoxic agents.

PAUCI-IMMUNE (VASCULITIC) DISEASE
Pauci-immune (vasculitic) GN is associated with the presence of antinuclear cytoplasmic antibodies (ANCAs). It can occur as either a renal-limited phenomenon or a component of a systemic vasculitis, as with Wegener granulomatosis, microscopic polyangiitis, or Churg-Strauss syndrome (see Plate 4-25). In contrast to ICGN, pauci-immune GN almost always produces RPGN, accounting for approximately 60% of total cases. It is an especially common cause of RPGN among older adults.
A characteristic finding of pauci-immune RPGN is a relative absence of immunofluorescent staining for antibodies and complement components. Although ANCAs are typical of pauci-immune GN, they may also be present in about one quarter of those with IC RPGN and one third of those with anti-GBM RPGN.
Pauci-immune RPGN is typically very aggressive. This management always includes steroids and cyclophosphamide, and severe cases warrant plasmapheresis. Untreated disease is usually fatal.

ANTI-GBM DISEASE
Anti-GBM disease occurs when autoantibodies directly target the glomerular basement membrane, causing inflammation that almost always leads to RPGN. Because anti-GBM disease (either isolated or as part of Goodpasture syndrome) is rare, however, it accounts for only 15% of total RPGN cases. A characteristic finding of anti-GBM disease is smooth, linear immunofluorescent staining of the capillary wall for antibodies and complement components. Treatment consists of plasmapheresis to remove the pathogenic antibodies, along with steroids and either cyclophosphamide or azathioprine. With treatment, mortality is about 10%. Without treatment, anti-GBM disease invariably produces end-stage renal disease (ESRD). Patients who deteriorate to the point of requiring dialysis may need to continue immunomodulatory treatment to prevent pulmonary hemorrhage, but treatment usually does not result in any recovery of renal function.

EVALUATION AND TREATMENT
When a patient has a rapid decline in renal function, complement levels and serologies should be obtained (ANA, anti-DNA antibodies, ANCA, anti-GBM anti-bodies, cryoglobulins, hepatitis B and C), and a renal biopsy should be performed without delay. Diseases with presentations similar to RPGN but with no evidence of crescents on biopsy include thrombotic microangiopathy and atheroembolic disease. If RPGN is strongly suspected, presumptive treatment with steroids is typically initiated at the time of presentation, with furt ertreatment dictated by the results of the renal biopsy.