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.
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.
