Glomerulonephritis: an overview of information

Glomerulonephritis is a group of diseases characterized by inflammatory changes, mainly in the glomeruli of the kidneys and associated symptoms of glomerulonephritis - proteinuria, hematuria, often retention of sodium and water, edema, hypertension, decreased kidney function.

The defeat of the glomeruli is combined with varying degrees of manifestation changes in tubulointerstitial space, especially with prolonged massive proteinuria. This aggravates the clinical manifestations (especially hypertension) and accelerates the progression of renal failure.

Glomerulonephritis can be primary (idiopathic), the clinical manifestations of which are limited only to the kidneys, or secondary - part of the systemic disease (usually systemic lupus erythematosus or vasculitis).

It should be noted that although glomerulonephritis can be presumed from clinical and laboratory data, a final diagnosis is possible only after a histological examination of the kidney tissue.

[1], [2], [3], [4], [5], [6], [7]

What causes glomerulonephritis?

The causes of glomerulonephritis are not known. In the development of some forms of glomerulonephritis, the role of infection - bacterial, especially nephritogenic strains of beta-hemolytic streptococcus group A (epidemics of acute poststreptococcal glomerulonephritis and today represent reality), viral, in particular hepatitis B and C viruses, HIV infection; medicinal preparations (gold, D-penicillamine); tumors and other factors of exogenous and endogenous origin.

Infectious and other stimuli induce glomerulonephritis, eliciting an immune response with the formation and deposition of antibodies and immune complexes in the glomeruli of the kidney and / or by enhancing the cell-mediated immune response. After initial damage, complement activation occurs, the involvement of circulating leukocytes, the synthesis of various chemokines, cytokines and growth factors, exclusion of proteolytic enzymes, activation of the coagulation cascade, and the formation of lipid mediator substances.

What causes glomerulonephritis?

Histopathology of glomerulonephritis

A complete diagnostic study of renal biopsy involves conducting light microscopy, electron microscopy, and examining immune deposits stained with immunofluorescent or immunoperoxidase.

Glomerulonephritis: Light microscopy

With glomerulonephritis, the dominant but not the only histological lesion is localized in the renal glomeruli. Glomerulonephritis is characterized as focal (focal) (if only certain glomeruli are affected) or as diffuse. In any particular glomerulus, the lesion can be segmental (exciting only a part of the glomerulus) or total.

In the study of a renal biopsy, errors may occur:

• associated with the size of the tissue sample: in biopsies of small size, one can make a mistake in determining the prevalence of the process;
• in sections that pass across the glomerulus, segmental lesions can be missed.

Damage can be hypercellular due to proliferation of endogenous endothelial or mesangial cells (called "proliferative cells") and / or infiltration by inflammatory leukocytes (called "exudative"). Severe acute inflammation causes necrosis in the glomeruli, often focal.

Thickening of the wall of the glomerular capillaries is due to an increase in the production of the material, which constitutes the basal membrane of the glomeruli (BMD), and the accumulation of immune deposits. For its detection, the color of the biopsy is useful by silvering, since silver stains the basal membranes and the other matrix in black. Coloring reveals, for example, the two-contouring of the basal membrane of the glomeruli due to the interposition of cells or an increase in the mesangial matrix not detected by other methods.

Segmental sclerosis is manifested by segmental collapse of capillaries with accumulation of hyaline material and mesangial matrix, often with attachment of capillary wall to Shumlyansky-Bowman capsule (formation of adhesion or "synechia").

Semi-moon (accumulation of inflammatory cells in the cavity of Shumlyansky-Bowman capsule) occurs in cases when severe glomerular damage leads to ruptures of the capillary wall or Bowman's capsule, allowing plasma proteins and inflammation cells to penetrate into Bowman's capsule space and accumulate. Semi-lunia consist of proliferating cells of parietal epithelium, infiltrating monocytes / macrophages, fibroblasts, lymphocytes, often with focal patchy fibrin.

The half moon has its name because of the appearance that they have on the slices of the kidney glomerulus. Semi-moon cause destruction of the glomeruli, rapidly increasing in size and squeezing the capillary bundle until its complete occlusion. After cessation of acute damage, the half moon is fibrotic, causing an irreversible loss of renal function. Semi-moon is a pathomorphological marker of fast-progressive glomerulonephritis, which develops most often with necrotic vasculitis, Goodpasture's disease, cryoglobulinemia, systemic lupus erythematosus due to infections.

Damage to glomerulonephritis is not limited to glomeruli. Often develops tubulointerstitsialnoe inflammation, more pronounced with active and severe glomerulonephritis. As the glomerulonephritis progresses and the glomeruli die, the tubules associated with them are atrophied, interstitial fibrosis is formed, a pattern characteristic of all chronic progressive kidney diseases.

Glomerulonephritis: Immunofluorescence microscopy

Immunofluorescent and immunoperoxidase staining is used to detect immune reactants in renal tissue. This is a routine method of searching for immunoglobulins (IgG, IgM, IgA), components of the classical and alternative complement activation pathways (usually C3, C4 and Clq), as well as fibrin, which is deposited in the semilunar and capillary thrombotic disorders (hemolytic-uremic and antiphospholipid syndrome) . Immune deposits are located along the capillary loops or in the mesangial region. They can be continuous (linear) or intermittent (granular).

Granular deposits in the glomeruli are often called "immune complexes," which means the deposition or local formation of antigen-antibody complexes in the glomeruli. The term "immune complexes" comes from work on experimental models of glomerulonephritis, where there is strong evidence of induction of glomerular damage by antigen-antibody complexes of known composition. However, in human jade, only in very rare cases it is possible to detect a potential antigen, and even more rarely it is possible to prove the deposition of the antigen together with the corresponding antibodies. Therefore, the broader term "immune deposits" is preferable.

Glomerulonephritis: Electron Microscopy

Electron microscopy is extremely important for assessing the anatomical structure of basal membranes (with some hereditary nephropathies, for example, Alport syndrome and nephropathy of thin basal membranes) and for localizing the location of immune deposits, which usually look homogeneous and electronically dense. Electron-dense deposits are observed in the mesangium or along the capillary wall on the subendothelial or subepithelial side of the basal membrane of the glomeruli. In rare cases, the electronically dense material is located linearly within the basal membrane of the glomeruli. The location of immune deposits in the glomeruli is one of the main signs in the classification of various types of glomerulonephritis.

Glomerulonephritis, in which the number of cells (hypercellularity) increases in the glomerulus, is called proliferative: it can be endocapillary (along with circulating inflammatory cells, the number of endothelial and mesangial cells has been increased) and extracapillary (the number of parietal epithelium cells that together with macrophages form characteristic arcuate thickening of the capsule of the glomerulus - semilunia).

Glomerulonephritis not older than a few weeks is called acute. If the duration of the disease is closer to a year or more, they talk about chronic glomerulonephritis. Glomerulonephritis with half-moon leads to kidney failure for several weeks or months, i.e. Is a rapidly progressive glomerulonephritis.

Forms of glomerulonephritis

Today, the classification of glomerulonephritis, as before, is based on the features of the morphological picture. There are several forms (variants) of histological damage that are observed in the study of renal biopsy with the help of light, immunofluorescence and electron microscopy. This classification of glomerulonephritis does not seem ideal, as it does not have a unique relationship between the morphological picture, the clinic, the etiology and pathogenesis of glomerulonephritis: the same histological variant may have a different etiology and a different clinical picture. Moreover, the same cause can cause a number of histological variants of glomerulonephritis (for example, a number of histological forms observed in viral hepatitis or systemic lupus erythematosus).

Forms of glomerulonephritis

[8], [9], [10], [11], [12], [13]

Treatment of glomerulonephritis

Treatment of glomerulonephritis sets itself the following tasks:

• to assess how great the activity and the probability of the progression of jade and whether they justify the risk of applying certain therapeutic effects;
• achieve reverse development of kidney damage (ideally - complete recovery);
• stop the progression of jade or at least slow the rate of increase in renal failure.

Treatment of glomerulonephritis