RPGN

Rapidly Progressive (Crescentic)

Glomerulonephritis
Rapidly progressive describes the clinical course
of several forms of glomerulonephritis (RPGN)
whose unifying feature is the histopathologic finding
of crescents in the majority of glomerul.
Therefore the terms rapidly progressive
glomerulonephritis (RPGN) and crescentic
glomerulonephritis (CGN) are synonymous.
The natural history of most forms of CGN is rapid
and relentless progression to end-stage renal failure.

Classification
CGN can be a severe manifestation of essentially
every defined primary and secondary GN, but
particular forms of GN are more likely to manifest as
RPGN or evolve into CGN.
If no underlying cause is identified by systemic
features, serologic testing, or histologic examination,
the disease is classified as idiopathic CGN.
Patients with systemic vasculitis appear to be
particularly prone to develop CGN.

 Patients with Henoch-Schonlein purpura (HSP), antineutrophil

cytoplasmic antibody (ANCA)mediated GN (microscopic
polyangiitis and Wegener granulomatosis), and systemic lupus
erythematosus (SLE) account for the majority of patients with
CGN.
Poststreptococcal GN rarely progresses to CGN, but because it
is the most common form of GN in childhood it accounts for a
significant percentage of patients with CGN in most reports.
Membranoproliferative GN and idiopathic cases make up most
of the remaining cases of CGN. Immunoglobulin (Ig)A
nephropathy, a common GN, only rarely is rapidly progressive.
Goodpasture disease often has rapidly progressive GN as a
component of the syndrome, but its rarity in childhood results
in its making up only a small percentage of children with CGN.

CLASSIFICATION OF RAPIDLY PROGRESSIVE (CRESCENTIC)

GLOMERULONEPHRITIS
ANTI-GBM ANTIBODYMEDIATED RPGN

Goodpasture syndrome
Idiopathic anti-GBM nephritis
Membranous nephropathy with crescents

RPGN ASSOCIATED
WITH GRANULAR
IMMUNE DEPOSITS

Postinfectious

Poststreptococcal glomerulonephritis

Bacterial endocarditis

Shunt nephritis

Visceral abscesses, other nonstreptococcal infections

Noninfectious

Systemic lupus erythematosus

Henoch-Schonlein purpura

Mixed cryoglobulinemia

Solid tumors

Primary renal disease

Membranoproliferative glomerulonephritis

IgA nephropathy

Idiopathic immune-complex nephritis

RPGN
WITHOUT
GLOMERULAR
IMMUNE
DEPOSITS

Vasculitis

Polyarteritis

Hypersensitivity vasculitis

Wegener granulomatosis

Idiopathic RPGN

Pathology and Pathogenesis

The hallmark of CGN is the histopathologic finding
of crescents in glomeruli.
Crescent formation, through proliferation of parietal
epithelial cells in Bowman's space, may be the final
pathway of any severe inflammatory glomerular
injury.
Fibrin deposition and macrophage infiltration in the
same areas suggest prominent involvement in the
pathogenesis of the epithelial cell proliferation.

 Fibrous crescents, in which proliferative cellular

crescents are replaced by collagen, are a late finding.
The immunofluorescence findings, as well as the pattern
of any deposits by electron microscopy (EM) can
delineate the underlying glomerulopathy in CGN
secondary to lupus, HSP nephritis, MPGN, postinfectious
GN, IgA nephropathy or Goodpasture disease.
Rare or absent findings by immunofluorescence and EM
typify pauci-immune GN (Wegener disease and
microscopic polyangiitis) and idiopathic crescentic GN.

Clinical Manifestations
Most children present with acute nephritis
(hematuria, some degree of renal insufficiency, and
hypertension) and usually have concomitant
proteinuria, often with nephrotic syndrome.
Occasional patients present late in the course of
disease with oliguric renal failure.
Extrarenal manifestations, such as pulmonary
involvement, joint symptoms, or skin lesions, can
help lead to the diagnosis of the underlying systemic
disease causing the CGN.

Diagnosis and Differential Diagnosis

The diagnosis of CGN is made by biopsy.
Delineation of the underlying etiology is reached by a
combination of additional biopsy findings (described
earlier), extrarenal symptoms and signs, and serologic
testing, including evaluation of antinuclear and antiDNA antibodies, serum complement levels, and ANCA.
If the patient has no extrarenal manifestations and a
negative serologic evaluation, and if the biopsy has no
immune or EM deposits, the diagnosis is idiopathic,
rapidly progressive CGN.

Prognosis and Treatment

Although the outcome is not uniformly positive,
children with rapidly progressive poststreptococcal GN
and CGN can spontaneously recover.
The natural course of the disease is far more severe in
the setting of other etiologies, including the idiopathic
category, and progression to end-stage renal failure
within weeks to months from onset is common.
Having a majority of fibrous crescents on the renal
biopsy portends a poor prognosis, because the disease
usually has progressed to irreversible injury.

 Although there are few controlled data, the consensus of most

nephrologists is that the combination of high-dose corticosteroids and
cyclophosphamide may be effective in preventing progressive renal
failure in patients with SLE, HSP nephritis, Wegener granulomatosis,
and IgA nephropathy if given early in the course when cellular
crescents predominate.
Although such therapy can also be effective in the other diseases
causing RPGN, renal outcomes in those settings are less favorable.
Progression to end-stage renal disease often occurs despite
aggressive immunosuppressive therapy.
In combination with immunosuppression, plasmapheresis has been
reported to benefit patients with Goodpasture disease.
However, the possible benefits of plasmapheresis in other forms of
RPGN are unclear.