MPGN

Membranoproliferative glomerulonephritis (MPGN), also known

as mesangiocapillary glomerulonephritis, most commonly
occurs in children or young adults.
MPGN can be classified into primary, idiopathic, and secondary
forms of glomerular disease.
Secondary forms of MPGN are most commonly associated with
subacute and chronic infection, including hepatitis B and C,
syphilis, subacute bacterial endocarditis, and infected shunts,
especially ventriculoatrial shunts (shunt nephritis).
MPGN can also be one of the glomerular lesions seen in lupus
nephritis

Pathology
MPGN is defined by the histologic pattern of glomeruli as seen by light,
immunofluorescence, and electron microscopy.
Two subtypes have been defined on histologic criteria and are associated
with different clinical phenotypes.
Type I MPGN is most common. Glomeruli have an accentuated lobular
pattern from diffuse mesangial expansion, endocapillary proliferation, and
an increase in mesangial cells and matrix.
The glomerular capillary walls are thickened, often with splitting from
interposition of the mesangium.
Crescents, if present, indicate a poor prognosis. Immunofluorescence
microscopy reveals C3 and lesser amounts of immunoglobulin in the
mesangium and along the peripheral capillary walls in a lobular pattern.
Electron microscopy confirms numerous deposits in the mesangial and
subendothelial regions.

 Far less common is type II MPGN, also called dense

deposit disease, which has similar light microscopic
findings as type I MPGN.
Differentiation from type I disease is by
immunofluorescence and electron microscopy.
In type II disease, C3 immunofluorescence typically is
prominent without concomitant immunoglobulin.
By electron microscopy, the lamina densa in the GBM
undergoes a very dense transformation, without evident
immune complextype deposits.

Pathogenesis
Because the histology of type I MPGN produced by
primary and secondary forms is indistinguishable, it
appears that this form occurs because circulating
immune complexes become trapped in the
glomerular subendothelial space, which then causes
injury, resulting in the characteristic proliferative
response and mesangial expansion.
Further evidence confirming this pathway to
glomerular injury is the finding of complement
activation through the classical pathway in as many
as 50% of affected patients.

 Type II MPGN appears to not be mediated by the immune complex.

The pathogenesis of the disease is not known, but the characteristic
finding of severely depressed serum complement levels suggests that
deranged complement regulation might play a major role in disease.
A typical finding is markedly depressed serum C3 complement levels,
with normal levels of other complement components.
In many patients with type II MPGN, C3 nephritic factor is present.
This factor activates the alternative complement pathway.
In unusual cases, patients with type II MPGN demonstrate an
associated systemic disease called partial lipodystrophy, where
there is diffuse loss of adipose tissue and decreased complement in
the presence of C3 nephritic factor.
Correlation among the presence of C3 nephritic factor, complement
levels, and disease presence or severity is not uniform or tightly
associated, indicating that the complement abnormalities alone are
not sufficient to cause the disease.

Clinical Manifestations
MPGN is most common in the 2nd decade of life.
Systemic features could provide clues to which type of
MPGN may be present in the secondary forms of the
disease, but the 2 histologic types of idiopathic MPGN are
indistinguishable on clinical grounds.
Patients present in equal proportions with nephrotic
syndrome, acute nephritic syndrome (hematuria,
hypertension, and some level of renal insufficiency), or
persistent asymptomatic microscopic hematuria and
proteinuria.
Serum C3 complement levels are low in the majority of
cases

Differential Diagnosis
The differential diagnosis includes all forms of acute and chronic
glomerulonephritis, including idiopathic and secondary forms, along
with postinfectious glomerulonephritis.
Postinfectious glomerulonephritis, far more common than MPGN,
usually does not have nephrotic features but typically has hematuria,
hypertension, renal insufficiency, and transient low C3 complement
levels, all features that may be seen with MPGN.
In contrast to MPGN, where C3 levels usually remain persistently low,
C3 returns to normal within 2 months after the onset of postinfectious
glomerulonephritis.
The diagnosis of MPGN is made by renal biopsy.
Indications for biopsy include nephrotic syndrome in an older child,
significant proteinuria with microscopic hematuria, and
hypocomplementemia lasting >2mo in a child with acute nephritis.

Prognosis and Treatment

determine whether MPGN is idiopathic or secondary to a
systemic disease, particularly lupus or chronic infection,
because treatment of the causative disease can result in
resolution of MPGN.
Untreated, idiopathic MPGN, regardless of type, has a
poor prognosis.
By 10yr after onset, 50% of patients with MPGN have
progressed to end-stage renal disease.
By 20yr after onset, up to 90% have lost renal function.

 Those with nephrotic syndrome at the time of presentation

progress to renal failure more rapidly.
No definitive therapy exists, but several reports, including a
randomized, controlled trial, indicate that extended courses
for years of alternate-day prednisone provide benefit.
Some patients treated with steroids enter complete remission
of their disease, but many have ongoing disease activity.
Nevertheless, an extended course of prednisone is associated
with significant preservation of renal function compared with
patients receiving no such treatment.