Membranous glomerulonephritis is a slowly progressive disease of the kidney
affecting mostly patients between ages of 30 and 50 years, usually Caucasian.
It is the second most common cause of nephrotic syndrome in adults, with focal
segmental glomerulosclerosis being the most common.
Terminology The closely related terms membranous
nephropathy and membranous glomerulopathy both refer to a similar
constellation but without the assumption of inflammation.
Membranous nephritis is less common, but the phrase is occasionally encountered.
These conditions are usually considered together.
By contrast, membranoproliferative glomerulonephritis has a similar name,
but is considered a separate condition with a distinctly different causality.
Membranoproliferative glomerulonephritis involves the basement membrane and
mesangium, while membranous glomerulonephritis involves the basement
membrane but not the mesangium. Signs and symptoms
Some people may present as nephrotic syndrome with proteinuria, edema with or
without renal failure. Others may be asymptomatic and may be picked up on
screening or urinalysis as having proteinuria. A definitive diagnosis of
membranous nephropathy requires a kidney biopsy.
Causes and classification = Primary/idiopathic =
85% of MGN cases are classified as primary membranous
glomerulonephritis—that is to say, the cause of the disease is idiopathic. This
can also be referred to as idiopathic membranous nephropathy. One study has
identified antibodies to an M-type phospholipase A2 receptor in 70% cases
evaluated. Other studies have implicated neutral endopeptidase and cationic
bovine serum albumin as antigens. = Secondary =
The remainder is secondary due to: autoimmune conditions
infections drugs.
inorganic salts. tumors, frequently solid tumors of the
lung and colon; hematological malignancies such as chronic lymphocytic
leukemia are less common. Pathogenesis
MGN is caused by immune complex formation in the glomerulus. The immune
complexes are formed by binding of antibodies to antigens in the glomerular
basement membrane. The antigens may be part of the basement membrane, or
deposited from elsewhere by the systemic circulation.
The immune complex serves as an activator that triggers a response from
the C5b - C9 complements, which form a membrane attack complex on the
glomerular epithelial cells. This, in turn, stimulates release of proteases
and oxidants by the mesangial and epithelial cells, damaging the capillary
walls and causing them to become "leaky". In addition, the epithelial
cells also seem to secrete an unknown mediator that reduces nephrin synthesis
and distribution. Morphology
The defining point of MGN is the presence of subepithelial
immunoglobulin-containing deposits along the glomerular basement membrane.
By light microscopy, the basement membrane is observed to be diffusely
thickened. Using Jones' stain, the GBM appears to have a "spiked" or "holey"
appearance. On electron microscopy, subepithelial
deposits that nestle against the glomerular basement membrane seems to be
the cause of the thickening. Also, the podocytes lose their foot processes. As
the disease progresses, the deposits will eventually be cleared, leaving
cavities in the basement membrane. These cavities will later be filled with
basement membrane-like material, and if the disease continues even further, the
glomeruli will become sclerosed and finally hyalinized.
Immunoflourescence microscopy will reveal typical granular deposition of
immunoglobulins and complement along the basement membrane.
Although it usually affects the entire glomerulus, it can affect parts of the
glomerulus in some cases. Treatment
Treatment of secondary membranous nephropathy is guided by the treatment
of the original disease. For treatment of idiopathic membranous nephropathy,
the treatment options include immunosuppressive drugs and non-specific
anti-proteinuric measures. Recommended first line therapy often includes:
cyclophosphamide alternating with a corticosteroid.
= Immunosuppressive therapy = Corticosteroids: They have been tried
with mixed results, with one study showing prevention of progression to
renal failure without improvement in proteinuria.
Chlorambucil Cyclosporine
Tacrolimus Cyclophosphamide
Mycophenolate mofetil Perhaps the most difficult aspect of
membranous glomerulonephritis is deciding which people to treat with
immunosuppressive therapy as opposed to simple "background" or anti-proteinuric
therapies. A large part of this difficulty is due to a lack of ability
to predict which people will progress to end-stage renal disease, or renal
disease severe enough to require dialysis. Because the above medications
carry risk, treatment should not be initiated without careful consideration
as to risk/benefit profile. Of note, corticosteroids alone are of little
benefit. They should be combined with one of the other 5 medications, each of
which, along with prednisone, has shown some benefit in slowing down progression
of membranous nephropathy. It must be kept in mind, however, that each of the
5 medications also carry their own risks, on top of prednisone.
The twin aims of treating membranous nephropathy are first to induce a
remission of the nephrotic syndrome and second to prevent the development of
endstage renal failure. A meta-analysis of four randomized controlled studies
comparing treatments of membranous nephropathy showed that regimes
comprising chlorambucil or cyclophosphamide, either alone or with
steroids, were more effective than symptomatic treatment or treatment with
steroids alone in inducing remission of the nephrotic syndrome.
Prognosis About a third of patients have
spontaneous remission, another third progress to require dialysis and the
last third continue to have proteinuria, without progression of renal failure.
References