Membranous

glomerulopathy

 Membranous glomerulopathy, now commonly called

membranous nephropathy (MN), a common cause of
nephrotic syndrome in adults, is a rare cause of nephrotic
syndrome in children.
MN is classified as the primary, idiopathic form, where
there is isolated renal disease, or secondary MN, where
nephropathy is associated with other identifiable systemic
diseases or medications.
In children, secondary MN is far more common than
primary, idiopathic MN. The most common etiologies of
secondary MN are systemic lupus erythematosus (SLE) or
chronic infections.

 Among the latter, chronic hepatitis B infection and congenital

syphilis are the best characterized and widely recognized causes
of MN.
However, other chronic infections have also been associated with
MN, including malaria, which is the most common cause of MN
worldwide.
Certain medications, such as penicillamine and gold, can also
cause MN.
Rarely, tumors, such as neuroblastoma, or other idiopathic
systemic diseases have been associated with MN.
Identification of secondary causes of MN is critical, because
removal of the offending agent or treatment of the causative
disease often leads to resolution of the associated nephropathy
and improves patient outcome.

Pathology
Glomeruli have diffuse thickening of the glomerular
basement membrane (GBM), without significant cell
proliferative changes.
Immunofluorescence and electron microscopy typically
demonstrate granular deposits of IgG and C3 located
on the epithelial side of the GBM in a spikelike pattern.
The GBM thickening presumably results from the
production of membrane-like material in response to
deposition of immune complexes.

Pathogenesis
MN is believed to be caused by in situ immune complex
formation.
Therefore, antigens from the infectious agents or
medications associated with secondary MN directly
contribute to the pathogenesis of the renal disease.
The causative agents or antigens in the other secondary
forms of MN have not been defined.
Likewise, the causative antigen in idiopathic MN is not
established, but the M-type phospholipase A2 receptor may
be a target antigen in idiopathic MN.

 This receptor, present on normal podocytes, is found

to be an antigen present in immune deposits
extracted from glomeruli from patients with
idiopathic MN.
The majority of idiopathic MN patients also
demonstrate circulating antibody against this
antigen.
Specific antigens trigger the onset of primary or
secondary MN, but genetic factors significantly
influence disease susceptibility and progression.

Clinical Manifestations
In children, membranous glomerulopathy is
most common in the 2nd decade of life, but it
can occur at any age, including infancy.
The disease usually manifests as nephrotic
syndrome and accounts for 2-6% of all cases of
childhood nephrotic syndrome.
Most patients also have microscopic hematuria
and only rarely present with gross hematuria.

 Approximately 20% of children have hypertension at

presentation.
A subset of patients with MN present with a major
venous thrombosis, commonly renal vein thrombosis.
This well-known complication of nephrotic syndrome
is particularly common in patients with MN.
Serum C3 and CH50 levels are normal, except in
cases of SLE, where levels may be depressed.

Diagnosis
Membranous glomerulopathy might be suspected on
clinical grounds, particularly in the setting of known risk
factors for secondary forms of the disease.
The diagnosis can only be established by renal biopsy.
No serologic test is specific for MN, but finding an active
carrier state for hepatitis B or congenital syphilis would
make the diagnosis probable in the appropriate clinical
setting.
Common indications for renal biopsy leading to the
diagnosis of MN include presentation with nephrotic
syndrome in a child >10yr or unexplained persistent
hematuria with significant proteinuria.

Prognosis and Treatment

Children presenting with asymptomatic, low-grade
proteinuria can enter remission spontaneously.
Although no controlled trials have been performed in
children, immunosuppressive therapy with an extended
course of prednisone can be effective in promoting complete
resolution of symptoms.
The addition of chlorambucil or cyclophosphamide appears
to provide further benefit to those not responding to steroids
alone.
For those unresponsive to immunosuppression, proteinuria
can be reduced with angiotensin-converting enzyme
inhibitors.