Causes and pathogenesis of acute poststreptococcal glomerulonephritis

For the first time acute poststreptococcal glomerulonephritis was described by Shick in 1907. He noted the presence of a latent period between scarlet fever and the development of glomerulonephritis and suggested a common pathogenesis of nephritis after scarlet fever and experimental serum sickness. After revealing the streptococcal cause of scarlet fever, the developing nephrite began to be considered an "allergic" response to the introduction of bacteria. Although nephritogenic species of streptococcus have been identified and characterized, the sequence of reactions leading to the formation of immune deposits and inflammation in the renal glomeruli has not yet been fully studied. Attention of many researchers was focused on the characteristics of these nephritogenic species of streptococci and their products, resulting in three main theories of the pathogenesis of acute poststreptococcal glomerulonephritis.

First, nephritogenic types of streptococci produce proteins - endostreptozins - with unique antigenic determinants that have a pronounced affinity for the structures of normal renal glomeruli. After entering the circulation, they bind to these parts of the glomeruli and become "implanted" antigens, which can directly activate the complement and with which antistreptococcal antibodies bind, forming immune complexes.

The second hypothesis suggests the possibility of damage to neuraminidase, secreted by streptococci, normal IgG molecules, which, because of this, become immunogenic and are deposited in intact glomeruli. These cationic IgGs, lacking sialic acids, become "implanted" antigens and, by binding to anti-IgG-AT (being a rheumatoid factor), form immune complexes. Recently, the possibility of antigenic mimicry between nephritogenic streptococci and antigens of normal renal glomeruli is being discussed. This hypothesis involves the development of antistreptococcal antibodies that cross-react with antigenic determinants normally located within the basal glomeruli membranes. It is believed that it can be antibodies to M-proteins, since it is these proteins that distinguish nephritogenic forms of streptococci from non-renhotogenic ones.

In patients with acute poststreptococcal glomerulonephritis, antibodies reacted with M-type streptococcal membrane antigens 12, and since these antibodies were absent in patients with streptococcal pharyngitis without nephritis, they were considered responsible for the development of glomerulonephritis. Nephritogenic properties are also expected in the surface proteins of M-type Streptococcus 6, which selectively bind to the proteoglycane-rich regions of the basal membrane of the glomeruli. Of nephritogenic streptococci, an antigen with MB 40-50 thousand Da and pi 4.7, called endostreptozin or water-soluble preabsorbing antigen (due to its ability to absorb antibodies from the serum of convalescents) is isolated. Elevated antibody titers to this antigen were found in 70% of patients with acute poststreptococcal glomerulonephritis.

Finally, the streptococcus cationic protease is isolated which has common epitopes with the human glomerular basement membrane and as a result has been found to be streptococcal pyrogenic (erythrogenic) endotoxin D. Cationic antigens are most likely as nephritis, as they easily penetrate the negatively charged filtration barrier and are localized in the subepithelial space. Anticontic response to cationic protease of streptococci (most often directed to its predecessor, zymogen with MB 44 thousand Da and pi 8.3) was detected in 83% of patients with acute poststreptococcal glomerulonephritis and is a much better marker of the disease than antibodies to DNAase B , hyaluronidase or streptokinase.

[1], [2], [3], [4], [5], [6], [7], [8], [9]

Morphological changes in acute poststreptococcal glomerulonephritis

In those cases when the diagnosis remains unclear, to clarify the cause of acute poststreptococcal glomerulonephritis, a kidney biopsy is performed. In patients with a nephrotic level of proteinuria in the kidney biopsy, mesangiocapillary can be more often detected than acute poststreptococcal glomerulonephritis. Early demarcation of these two diseases is extremely necessary, since for mesangiocapillary glomerulonephritis, especially in children, a completely different therapeutic approach is used - "aggressive" immunosuppressive therapy.

Morphological picture of acute diffuse proliferative post-streptococcal glomerulonephritis

Inflammation	Proliferation	Immune deposits
At the onset of the disease - the glomeruli infiltrate polymorphonuclear neutrophils, eosinophils, macrophages ("exudation phase") At the height of the disease - macrophages	Intra-Caminoid: often Half moon: more often focal, less common	IgG, C3, properdin, diffuse granular type of sediment ("starry sky" in the early stages, "garlands" - at later stages), subepithelial "humps," subendothelial and mesangial deposits

The most typical changes are observed in the material of biopsies performed at the very beginning of the disease: hypercellularity of glomeruli with varying degrees of infiltration of capillary loops and mesangial region by polynucleated leukocytes, monocytes and eosinophils. In cases of predominance of the proliferation of mesangial and endothelial cells, the term "proliferative nephritis" is used. In cases where the prevalence of polynucleon leukocyte infiltration, the term "exudative glomerulonephritis" is used. With the expressed proliferation of parietal epithelium and the accumulation of monocytes in extracapillary space, extracapillary glomerulonephritis (glomerulonephritis with "semilunar") is diagnosed. In this case, focal and segmental semilunes are usually observed; diffuse extracapillary glomerulonephritis with the formation of half-moons in more than 50% of the glomeruli is rare and foreshadows an unfavorable prognosis.