Membranoproliferative glomerulonephritis (MPGN) is a type of

glomerulonephritis Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the ...

caused by deposits in the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

glomerular

mesangium The glomerulus (plural glomeruli) is a network of small blood vessels (capillaries) known as a ''tuft'', located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally ...

and basement membrane ( GBM) thickening, activating

complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-clas ...

and damaging the glomeruli. MPGN accounts for approximately 4% of primary renal causes of

nephrotic syndrome Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy ...

in children and 7% in adults. It should not be confused with membranous glomerulonephritis, a condition in which the basement membrane is thickened, but the mesangium is not.

Type

There are three types of MPGN, but this classification is becoming obsolete as the causes of this pattern are becoming understood.

Type I

Type I, the most common by far, is caused by immune complexes depositing in the kidney. It is characterised by subendothelial and mesangial immune deposits. It is believed to be associated with the

classical complement pathway The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune system. The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and ...

Type II

Also called recently as ‘C3 nephropathy’ The preferred name is "dense deposit disease." Most cases of dense deposit disease do not show a membranoproliferative pattern. A 2012 review considers DDD to be in a continuum with

C3 glomerulonephritis Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the ...

, one reason the use of the type I to type III classification system is falling out of favour. Most cases are associated with the dysregulation of the

alternative complement pathway The alternative pathway is a type of cascade reaction of the complement system and is a component of the innate immune system, a natural defense against infections. The alternative pathway is one of three complement pathways that opsonize and ...

. DDD is associated with deposition of complement C3 within the glomeruli with little or no staining for immunoglobulin. The presence of C3 without significant immunoglobulin suggested to early investigators that DDD was due to abnormal activation of the complement alternative pathway (AP). There is now strong evidence that DDD is caused by uncontrolled AP activation. Spontaneous remissions of MPGN II are rare; approximately half of those affected with MPGN II will progress to end stage renal disease within ten years. In many cases, people with MPGN II can develop

drusen Drusen, from the German word for ''node'' or ''geode'' (singular, "Druse"), are tiny yellow or white accumulations of extracellular material that build up between Bruch's membrane and the retinal pigment epithelium of the eye. The presence of a ...

caused by deposits within

Bruch's membrane Bruch's membrane is the innermost layer of the choroid of the eye. It is also called the ''vitreous lamina'' or ''Membrane vitriae'', because of its glassy microscopic appearance. It is 2–4 μm thick. Layers Bruch's membrane consists of five l ...

beneath the

retinal pigment epithelium The pigmented layer of retina or retinal pigment epithelium (RPE) is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells, and is firmly attached to the underlying choroid and overlying retinal visual ce ...

of the eye. Over time, vision can deteriorate, and subretinal neovascular membranes, macular detachment, and

central serous retinopathy Central serous chorioretinopathy (CSC or CSCR), also known as central serous retinopathy (CSR), is an eye disease that causes visual impairment, often temporary, usually in one eye. When the disorder is active it is characterized by leakage of f ...

can develop.

Type III

Type III is very rare, it is characterized by a mixture of subepithelial and subendothelial immune and/or complement deposits. These deposits elicit an immune response, causing damage to cells and structures within their vicinity. Has similar pathological findings of Type I disease. A candidate gene has been identified on

chromosome 1 Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non- sex chromosomes. Chromosome 1 spans about 249 million nucleotide base pairs, which ...

Complement component 3 Complement component 3, often simply called C3, is a protein of the immune system. It plays a central role in the complement system and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene called ''C3''. Function C ...

is seen under

immunofluorescence Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to spe ...

. it is associated with complement receptor 6 deficiency.

Pathology

Membranoproliferative glomerulonephritis involves deposits at the intraglomerular mesangium. It is also the main

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, ...

associated nephropathy. It also is related to a number of autoimmune diseases, prominently

systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Commo ...

(SLE), Class IV. Also found with

Sjögren syndrome Sjögren syndrome or Sjögren's syndrome (SjS, SS) is a long-term autoimmune disease that affects the body's moisture-producing (lacrimal and salivary) glands, and often seriously affects other organ systems, such as the lungs, kidneys, and nerv ...

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...

, inherited complement deficiencies (esp C3 deficiency),

scleroderma Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs. The disease can be either localized to the skin or involve other organs, as well. Symptoms may include areas ...

Celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

. The histomorphologic

differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...

includes transplant glomerulopathy and thrombotic microangiopathies.

Diagnosis

The GBM is rebuilt on top of the deposits, causing a " tram tracking" appearance under the microscope. Mesangial cellularity is increased.

Treatment

Primary MPGN is treated with steroids, plasma exchange and other immunosuppressive drugs. Secondary MPGN is treated by treating the associated infection, autoimmune disease or neoplasms. Pegylated interferon and ribavirin are useful in reducing viral load.

References

External links

* *
Membranoproliferative_GN
a

MP GN Pathophysiology
discusses the nephritic auto-antibodies/factors {{Glomerular disease Nephrology Hepatitis C virus-associated diseases