Glomerulonephritis (GN) refers to several types of kidney diseases. Most of CN are characterized by inflammation either of the glomeruli or of the small blood vessels in the kidneys. Mesangial proliferative glomerulonephritis (MPGN) is a form of glomerulonephritis associated primarily with the mesangium. Although rare, it is a condition that has an impact on the kidney. It is considered a separate condition and may present with nephrotic syndrome that includes proteinuria, low blood protein level, high cholesterol level swelling, and hematuria. It is classified by the World Health Organization (WHO) as type II lupus nephritis. Some evidence suggests that interleukin-10, recognized to have potent and broad-spectrum anti-inflammatory activity, may inhibit MPGN.
Fig 1. Mesangial proliferative glomerulonephritis.1
Causes
Most cases of mesangial proliferative glomerulonephritis are linked to IgA nephropathy (IgAN), a form of glomerulonephritis or inflammation of the glomeruli of the kidney. Generally, IgAN has been known to be the most common type of glomerulonephritis all over the world. Mesangial cell proliferation, which characterizes MPGN, constitutes a frequent finding in a variety of glomerular diseases. It may be found in IgAN and several diseases including IgM nephropathy (IgMN), lupus nephritis (caused by lupus), Alport’s syndrome, and postinfectious glomerulonephritis.
MPGN is related to a variety of kidney disorders, some of which may run in families. So far, there are no specific genes identified as responsible for MPGN. Genetic predisposition may be considered a risk factor. Most cases of MPGN are linked with IgA nephropathy, which is regarded as an autoimmune disease. For some people, IgAN runs in families. Therefore, genetic predisposition may contribute to the MPGN. Complement C2 and C3 contribute to the pathogenesis of glomerulonephritis.
Diagnosis
For the MPGN patients, the peripheral capillary walls are thin and delicate without obvious deposits, reduplication, focal disruptions, or cellular necrosis. The visceral and parietal epithelial cells have not undergone proliferation, although they are occasionally enlarged. Crescents and segmental sclerosis should be absent just for the occurrence of MPGN. The tubulointerstitium and vasculature may show nothing abnormal, except the fact that reduced renal function or hypertension is present or the patient is of advanced age.
The number of mesangial cells increases on electron microscopy when infiltrating monocyte or polymorphonuclear leukocyte can also be occasionally observed. The amount of mesangial matrix is commonly diffusely increased. Electron-dense deposits within the mesangium can be observed in many cases, particularly those with immunoglobulin (IgG, IgM, or IgA) deposits on immunofluorescence microscopy. Very large mesangial or paramesangial electron-dense deposits indicates IgA nephropathy even without the availability of immunofluorescence microscopy. Subendothelial and subepithelial deposits are not observed for MPGN. If present, they indicate a post-infectious etiology or underlying lupus nephritis. Deposits of multiple immunoglobulin classes identified by immunohistology and large numbers of tubuloreticular inclusions on electron microscopy suggest underlying lupus nephritis.
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Reference
1. From Wikipedia: Nephron - Own work, CC BY-SA 3.0 https://commons.wikimedia.org/wiki/File:Membranoproliferative_glomerulonephritis_-_very_high_mag.jpg.
Questions & Answer
A: Emerging therapies include novel complement inhibitors, gene therapies, and small molecules. Some promising candidates include AMY-101 which targets the alternative pathway and gene-editing techniques to correct complement dysregulation at the genetic level.
A: In glomerulonephritis, the complement system's central components involved are C3 and C5. Dysregulation of these components can lead to the formation of complement complexes, which deposit in the glomeruli and trigger inflammation. This inflammation damages the kidney's filtration units, leading to proteinuria, hematuria, and reduced kidney functions.
A: Yes, emerging therapies in complement modulation for glomerulonephritis include novel agents that target specific complement components or pathways. For example, inhibitors of Factor D, a key component of the alternative complement pathway, are being investigated. Additionally, research into gene therapy and personalized medicine approaches to correct complement dysregulation is gaining momentum.
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