Pathophysiology of Post-Infectious Glomerulonephritis
Immune Complex-Mediated Mechanism
Post-infectious glomerulonephritis (PIGN) is fundamentally an immune complex-mediated disease where streptococcal antigens trigger immune complex deposition in glomerular tissue, causing inflammation and kidney damage. 1
The pathophysiologic cascade involves several key steps:
Streptococcal Antigens and Immune Activation
- Nephritis-associated plasmin receptor (NAPlr), identified as glyceraldehyde-3-phosphate dehydrogenase, is one of the two leading streptococcal antigens involved in the pathogenesis. 2
- Streptococcal pyrogenic exotoxin B (SPeB), a cationic cysteine proteinase, is the second major antigen implicated in triggering the immune response. 2, 3
- Both NAPlr and SPeB have a high affinity for plasmin and glomerular proteins, which facilitates their deposition in the glomerulus. 3
Complement Activation and Glomerular Injury
- The immune complexes activate the complement system primarily via the alternative pathway, though the lectin pathway also contributes. 2, 4
- This complement activation is critical for generating inflammation by the immune complexes deposited in the glomerulus. 2
- The result is low serum C3 complement levels, which is a hallmark laboratory finding in PIGN. 3
Temporal Relationship to Infection
- The disease typically occurs 1-3 weeks after streptococcal pharyngitis or 4-6 weeks after impetigo, representing a latency period during which the immune response develops. 1
- This delayed presentation distinguishes PIGN from direct infectious injury and confirms its immune-mediated nature. 1
Histopathologic Changes
- The glomeruli are diffusely affected, presenting with enlarged glomerular tufts due to hypercellularity. 2
- Proliferative endothelial and mesangial cells along with inflammatory cell infiltration are characteristic findings. 2
- The inflammation results in the classic features of acute nephritic syndrome, including hematuria with red blood cell casts, proteinuria, hypertension, edema, and oliguria. 1, 4
Clinical Pitfalls
- The pathogenesis is not fully understood despite recent advances, and ongoing research continues to identify additional antigens and mechanisms. 2
- While group A β-hemolytic streptococcus (Streptococcus pyogenes) is the classic trigger, non-streptococcal organisms are emerging as main etiological agents in high-income countries, particularly staphylococcal infections in adults. 3
- The immune response can occasionally lead to severe complications including rapidly progressive glomerulonephritis with crescent formation, though this is uncommon. 4, 5