What is the pathophysiology of poststreptococcal glomerulonephritis?

Updated: Dec 16, 2020
  • Author: Duvuru Geetha, MD, MRCP; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Poststreptococcal glomerulonephritis follows infection with only certain strains of streptococci, designated as nephritogenic. The offending organisms have virtually always been group A streptococci. Acute poststreptococcal glomerulonephritis (APSGN) follows pyodermatitis with group A streptococci that have the surface antigen M protein types 47, 49, 55, 2, 60, and 57 and throat infection with streptococci that have M types 1, 2, 4, 3, 25, 49, and 12. Less often, group C streptococci (ie, Streptococcus zooepidemicus) may be involved. [6]

Many morphologic, clinical, and serologic features suggest that APSGN is an immune complex disorder in which an immune complex containing a streptococcal antigen is deposited in the affected glomeruli. The size of glomerular basement membrane (GBM) pores and the molecular size of the streptococcus-Ig complex are also important determinants. The molecular size of the streptococcus-Ig complex is about 15 nm (10 nm for streptococcus group A and 5 nm for immunoglobulin). The GBM pore sizes in children and adults are 2-3 nm and 4-4.5 nm, respectively. Therefore, the immune complex molecule can be more easily rodded into the glomerulus in children than in adults and, thus, may explain the higher frequency of APSGN in children than in adults.

Stamatiades et al determined that in PSGN and other type III hypersensitivity reactions, vascular endothelial cells in the kidney actively transport circulating immune complexes from the capillaries to the peritubular interstitial space, where they are detected and scavenged by resident macrophages. Uptake of the immune complexes by the resident macrophages triggers the release of pro-inflammatory cytokines, which in turn results in recruitment of monocytes and neutrophils into the kidney from the circulation. [7]

Two antigens isolated from nephritogenic streptococci are commonly implicated in APSGN: streptococcal pyrogenic exotoxin B (SPEB) and nephritis-associated plasmin receptor (NAPlr). [8, 9] Both SPEB and NAPlr bind plasmin, protecting it from physiological inhibitors, and thus could cause chemotaxis of inflammatory cells and degradation of glomerular basement membranes. Both can be found in the glomeruli of APSGN tissues [9] .

In addition to streptococcal antigens, rheumatoid factor, cryoglobulins, and antineutrophil cytoplasmic serum antibodies are present in some of these patients. The pathogenic significance of this autoimmune response is not defined.

There are also host susceptibility factors. In one study, HLA-DRB1*03011 was reported to be found at a significantly higher frequency in 32 unrelated patients with APSGN as compared to 380 healthy individuals. [10]

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