What is the primary pathophysiology of post-streptococcal glomerulonephritis (PSGN)?

Primary Pathophysiology of Post-Streptococcal Glomerulonephritis

The primary pathophysiology of post-streptococcal glomerulonephritis involves immune complex deposition in glomerular tissue, causing inflammation and subsequent kidney damage. 1

Immune Complex-Mediated Mechanism

Post-streptococcal glomerulonephritis (PSGN) is the prototypical infection-related acute glomerulonephritis, occurring 1-3 weeks after streptococcal pharyngitis or impetigo. The pathogenesis follows a specific immunological process:

• Immune complexes form either in circulation or in situ on the glomerular basement membrane following infection with nephritogenic strains of group A beta-hemolytic streptococci 2
• These immune complexes activate the complement system, particularly the alternative pathway, triggering glomerular inflammation 3
• Characteristic subendothelial immune complex deposits (known as "humps") can be observed on electron microscopy 4
• The immune complexes contain streptococcal antigens and corresponding antibodies, which become trapped in the glomerular filtration barrier 5

Role of Nephritogenic Antigens

Recent research has identified specific streptococcal antigens involved in PSGN pathogenesis:

• Nephritis-associated plasmin receptor (NAPlr) has been isolated from group A streptococcus and found deposited in glomeruli of PSGN patients 6
• NAPlr functions as a plasmin receptor, maintaining plasmin activity in the glomeruli, which may contribute to tissue damage through a direct, non-immunologic mechanism 6
• Glomerular plasmin activity is detected in a distribution nearly identical to NAPlr deposition in renal biopsy tissues of PSGN patients 6
• Nephritogenic antigens can induce inflammatory processes early, even before immune complex formation is complete 2

Inflammatory Response and Cellular Mechanisms

The inflammatory cascade in PSGN involves both innate and adaptive immune responses:

• Infiltration of inflammatory cells including neutrophils, monocytes/macrophages, and lymphocytes (CD4+ and CD8+) into the glomeruli 2
• Activation of complement leads to the release of chemotactic factors that attract inflammatory cells 3
• The resulting inflammation causes increased glomerular permeability, leading to proteinuria and hematuria 5
• Cellular proliferation within the glomeruli contributes to the characteristic diffuse proliferative glomerulonephritis pattern seen on histology 4

Progression and Resolution

While most cases of PSGN resolve spontaneously, some progress to chronic kidney disease:

• Failure to induce apoptosis and clear apoptotic cells may lead to membrane permeabilization and release of pro-inflammatory molecules, perpetuating renal inflammation 2
• Other factors contributing to chronicity include persistent infection, genetic background of the host's complement system, tubulointerstitial changes, and pre-existing kidney damage 2
• The disease typically presents with features of acute nephritic syndrome, but can occasionally progress to more severe manifestations including hypertensive emergencies, congestive heart failure, or rapidly progressive glomerulonephritis 3

Clinical Implications

Understanding this immune complex-mediated pathophysiology guides management:

• Treatment focuses on supportive care, with antibiotics (penicillin or erythromycin if penicillin-allergic) to eliminate streptococcal infection and decrease antigenic load 1
• Management of nephritic syndrome includes diuretics, antihypertensives, and supportive care 1
• Corticosteroids are generally reserved for severe crescentic glomerulonephritis based on anecdotal evidence 1
• Most patients recover fully, but some require monitoring for persistent proteinuria, hypertension, or progression to chronic kidney disease 3