What are the clinical manifestations and pathophysiology of Post-Streptococcal Glomerulonephritis (PSGN)?

Post-Streptococcal Glomerulonephritis: Pathophysiology and Clinical Manifestations

Pathophysiology

PSGN is an immune complex-mediated disease where streptococcal antigens trigger immune complex deposition in glomerular tissue, activating the complement system and causing glomerular inflammation and subsequent kidney damage. 1, 2

Immunologic Mechanism

• The disease involves deposition of immune complexes in the glomeruli following infection with nephritogenic strains of group A β-hemolytic Streptococcus (Streptococcus pyogenes) 3, 4
• Two key streptococcal antigens are implicated: nephritis-associated plasmin receptor (identified as glyceraldehyde-3-phosphate dehydrogenase) and the cationic cysteine proteinase streptococcal pyrogenic exotoxin B 4
• The complement system is activated primarily via the alternative pathway, though the lectin pathway also contributes, generating inflammation at sites of immune complex deposition 5, 4
• This immune-mediated process results in acute diffuse proliferative glomerulonephritis 4

Temporal Relationship

• PSGN typically occurs 1-3 weeks after streptococcal pharyngitis 1, 6
• Following impetigo (skin infection), the latency period extends to 4-6 weeks 1

Histopathologic Features

• Glomeruli are diffusely affected with enlarged glomerular tufts due to hypercellularity 4
• Endocapillary hypercellularity is present, characterized by increased numbers of cells within glomerular capillary lumina causing luminal narrowing 7
• Mesangial proliferation with proliferative endothelial and mesangial cells is observed 4
• Subepithelial "humps" (electron-dense deposits) are typically seen on electron microscopy in infection-related glomerulonephritis 7
• Exudative patterns may occur with neutrophils accounting for >50% of glomerular hypercellularity 7
• In severe cases, crescentic glomerulonephritis with cellular, fibrocellular, or fibrous crescents may develop 7

Clinical Manifestations

The classic presentation is acute nephritic syndrome occurring 1-3 weeks post-pharyngitis or 4-6 weeks post-impetigo, characterized by hematuria with red blood cell casts, hypertension, edema, and oliguria. 1, 5

Cardinal Features of Nephritic Syndrome

• Hematuria: Microscopic or gross (red to brown "tea-colored" or "cola-colored" urine) with glomerular red blood cell casts on urinalysis 1, 3, 5
• Hypertension: Present in approximately 95% of patients in the acute phase, typically mild and short-term 8
• Edema: Periorbital and peripheral edema due to sodium and water retention 3, 5
• Oliguria: Reduced urine output secondary to decreased glomerular filtration 3, 5

Laboratory Abnormalities

• Proteinuria: Ranges from mild to nephrotic range (>3.5 g/day or protein-creatinine ratio >3.5) 1, 3
• Acute kidney injury: Elevated serum creatinine and decreased estimated glomerular filtration rate (eGFR), which can be severe (GFR as low as 11.2 ml/min/1.73 m² in severe cases) 3
• Low C3 complement: Hallmark finding that should normalize within 8-12 weeks; persistently low C3 beyond 12 weeks warrants kidney biopsy to exclude C3 glomerulonephritis 1, 6
• Normal C4 complement: Helps differentiate PSGN from other forms of glomerulonephritis 1
• Elevated streptococcal antibodies: Anti-streptolysin O (ASO), anti-DNAse B, and anti-hyaluronidase titers 1, 3
• Hyperuricemia: May be present in severe cases 3

Severe Complications

• Hypertensive emergencies: Require urgent blood pressure control 5
• Congestive heart failure: Due to volume overload and hypertension 5
• Severe acute kidney injury: May necessitate dialysis 1, 5
• Rapidly progressive glomerulonephritis: Crescentic disease with rapid decline in renal function 5
• Nephrotic syndrome: Occasionally presents with heavy proteinuria, hypoalbuminemia, and edema 5

Clinical Presentation Variability

• Presentation ranges from asymptomatic microscopic hematuria discovered incidentally to full nephritic syndrome with complications 9, 4
• Fatigue, shortness of breath, and signs of fluid overload may be present 7
• In the context of ongoing infection, patients may show signs of sepsis with very high inflammatory markers 3

Long-Term Manifestations

• Hypertension persisting beyond the acute phase (present in approximately 6.8% of patients at 2-5 years follow-up) is a poor prognostic sign associated with development of glomerulosclerosis and potential progression to chronic kidney disease 8
• Persistent proteinuria and hematuria may require long-term monitoring 5