Membranous glomerulonephritis (membranous nephropathy) – causes & symptoms

Membranous glomerulonephritis, also known
as membranous nephropathy, is where the glomerular basement membrane, or GBM, which lines the
glomeruli in the kidney, becomes inflamed and damaged, which results in increased permeability
and proteins being able to filter through into the urine, causing nephrotic syndrome. But what exactly is nephrotic syndrome? Well usually the glomerulus only lets small
molecules, like sodium and water, move from the blood into the kidney nephron, where it
eventually makes its way into the urine. But with nephrotic syndromes, the glomeruli
are damaged and they become more permeable, so they start letting plasma proteins come
across from the blood to the nephron and then into the urine, which causes proteinuria,
typically greater than 3.5 grams per day. An important protein in the blood is albumin,
and so when it starts leaving the blood, people get hypoalbuminemia—low albumin in the blood. With less protein in the blood the oncotic
pressure falls, which lowers the overall osmotic pressure, which drives water out of the blood
vessels and into the tissues, called edema. Finally, it’s thought that as a result of
either losing albumin or losing some protein or proteins that inhibit the synthesis of
lipids, or fat, you get increased levels of lipid in the blood, called hyperlipidemia. Just like the proteins, these lipids can also
get into the urine, causing hyperlipiduria. And those are the hallmarks of nephrotic syndrome—proteinuria,
hypoalbuminemia, edema, hyperlipidemia, and lipiduria. Alright, so with membranous glomerulonephritis,
the basement membrane becomes damaged which causes nephrotic syndrome. How does this happen, though? Well, ultimately this damage is caused by
immune complexes—complexes composed of an antigen with an antibody bound to it. One way these complexes can form is as a result
of autoantibodies directly targeting the glomerular basement membrane. Two major antigen targets that’ve been identified
are the M-type phospholipase A2 receptor and neutral endopeptidase, which are both expressed
on the podocyte surface—the cells that line the basement membrane, and we know this because
a large proportion of cases, people with membranous glomerulonephritis have antibodies against
these autoantigens in their bloodstream. Immune complexes, though, might also form
outside of the kidney, and then get carried through the bloodstream to the glomerulus
and deposit in the basement membrane. One potential circulating antigen that’s
been identified is cationic bovine serum albumin, which is present in cow’s milk and beef
protein, and can escape the intestinal barrier, cause immune complex formation, and deposit
in the GBM. Whether they bind directly to the GBM, or
come from somewhere else, these immune complexes are called subepithelial deposits because
they’re sandwiched right between the epithelial cells or podocytes, and the GBM. These subepithelial deposits are thought to
activate the complement system, which is a cascade of enzyme activation that ultimately
produces the membrane attack complex, which directly damages both the podocytes as well
as mesangial cells, which are the cells that work to remove trapped residue and debris. The immune reaction also recruits inflammatory
cells that release proteases and oxidants, which damage the basement membrane and cause
it to become “leaky”, allowing proteins to filter through into the urine, which causes
the signs and symptoms of nephrotic syndrome. Over time, as a reaction to the immune deposits,
GBM matrix is deposited in between the immune complexes, which makes the GBM appear thickened
on histology. If you take a closer look on electron microscopy,
you’ll see that this pattern of GBM matrix on the subepithelial deposits creates a characteristic
“spike and dome” pattern, and you also see effacement or flattening of the foot processes
of the podocytes. Finally, on immunofluorescence you’ll see
deposits of immune complexes, which appear as granular or sort of sprinkled throughout
the GBM. Membranous glomerulonephritis most commonly
affects caucasian adults, and it can be primary, or idiopathic, meaning it’s not quite clear
why these complexes form, and this accounts for the vast majority of cases. The rest of cases, though, are secondary,
and seem to arise from autoantibodies that are generated in response to another process
like an infection, malignancies, autoimmune conditions, or medications. If it is secondary to some other disease,
then usually treatment starts by treating the underlying disease. If it’s primary or idiopathic, then steroids
are sometimes used, but they’ve been shown to have mixed results. If it goes untreated or the treatment is not successful, then membranous glomerulonephritis can progress to chronic renal failure. Alright, quick recap—membranous glomerulonephritis
is where immune complexes deposit in the GBM, causing a thickening of that GBM and a “spike
and dome” appearance that leads to nephrotic syndrome. Thanks for watching, you can help support
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