The nephritic syndrome

1. Definition

• Set of clinical signs/symptoms with acute onset from glomerular inflammation.

2. Clinical Features

• Hematuria with dysmorphic RBCs (± RBC casts)
• Hypertension (fluid retention)
• Mild proteinuria + mild edema (less than nephrotic)
• Some oliguria + azotemia

3. Morphology (overview)

• Proliferation of glomerular cells (endothelial + mesangial).
• Leukocyte infiltration → capillary wall injury → RBC leak (hematuria) → ↓ GFR → oliguria, azotemia.

4. Causes

• Post-infectious GN — prototype: post-streptococcal GN.
• Primary GN — prototype: IgA nephropathy (Berger disease).

5. Acute Post-Infectious (Post-Streptococcal) GN

Etiology

• Classic: group A β-hemolytic Streptococcus (nephritogenic strains).
• Also: pneumococcal, staphylococcal, viral (HBV, HCV) antigens.

Pathogenesis

• Circulating immunocomplexes (bacterial Ag + Ab) deposit in glomerulus.
• Classic location: subepithelial “humps”.
• Complement activation → inflammatory cell recruitment → cellular injury → proliferation.
• IF: granular deposits of IgG + C3.
• Differentiate from rheumatic fever: in rheumatic fever, tonsillitis → anti-Streptococcal Abs cross-react with heart antigens (molecular mimicry) → not GN.

Morphology

• Subepithelial “humps” (EM): immune complex deposits.
• Glomerular hypercellularity: endothelial + mesangial proliferation + neutrophil + monocyte infiltration.
• IF: granular IgG + C3 along GBM and mesangium.

Clinical course

• Begins as upper respiratory tract infection (S. pyogenes) or pharyngitis/impetigo.
• 2–3 weeks later: abrupt kidney disease + malaise, fever, nausea, nephritic features (oliguria, hematuria, azotemia, mild HTN, mild edema).
• Labs: ↓ C3, ↑ ASO titer, anti-DNase B.
• Prognosis: majority recover completely (especially children, via macrophage clearance).
  • ~2 % progress to RPGN
  • 10–50 % to chronic GN (more often in adults)

6. IgA Nephropathy (Berger Disease)

Definition

• Most common primary GN worldwide; characterized by mesangial IgA deposits.
• Presents with macroscopic hematuria within 1–2 days of a non-specific URTI (synpharyngitic).

Pathogenesis

• Abnormality in IgA production + clearance.
  • IgA = main mucosal Ig; serum ↑ from increased production.
  • Abnormal galactosylation of IgA1 → stickier IgA.
• High IgA deposits in mesangium → activation of alternative complement pathway (no C1q/C4) → glomerular injury.

Morphology

• Mesangial widening + cell proliferation.
• IF: mesangial IgA + C3 deposits.

Clinical course

• Affects children + young adults.
• 10–15 % → nephritic syndrome.
• 25–50 % → slow progression to chronic GN.
• Related entity: Henoch-Schönlein purpura = IgA nephropathy + skin purpura + arthritis + abdominal pain in children.

7. Post-strep vs IgA — Quick Comparison

Feature	Post-strep GN	IgA nephropathy
Onset post-infection	2–3 weeks after	1–2 days after (synpharyngitic)
Age	Children	Children + young adults
Deposit	Subepithelial humps (IgG + C3)	Mesangial IgA + C3
Complement	↓ C3 (classical pathway)	Normal C3 (alternative pathway local)
Serology	↑ ASO, anti-DNase B	None specific
Prognosis	Mostly recover	25–50 % progress to chronic GN

💡 High-yield: Nephritic = hematuria + HTN + mild proteinuria + oliguria/azotemia. Post-strep GN: 2–3 wk after pharyngitis (impetigo), subepithelial humps, ↓ C3, ↑ ASO, kids, usually self-resolve. IgA nephropathy (Berger): 1–2 d after URTI, mesangial IgA deposits, alternative pathway, recurrent hematuria, 25–50 % → chronic GN. HSP = IgA nephropathy + purpura + arthritis + abdominal pain.