IgA nephropathy

Etiology

• IgA nephropathy is the most common primary glomerulonephritis in adults.
• Peak incidence: 20-30 years old

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Pathophysiology

An increased number of defective, circulating IgA antibodies are synthesized (often triggered by mucosal infections, i.e., upper respiratory tract and gastrointestinal infections) → IgA antibodies form immune complexes that deposit in the renal mesangium → mesangial cell and complement system activation → glomerulonephritis (type III hypersensitivity reaction)

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Clinical features

• Recurring episodes of:
  • Gross or microscopic hematuria
  • Flank pain
  • Low-grade fever
  • And/or nephritic syndrome (including hypertension)
  • Usually during or immediately following a respiratory or gastrointestinal infection
• Can progress to RPGN and/or nephrotic syndrome (< 10% of patients)
• Up to 50% of patients progress to end-stage renal disease within 20–25 years.

Tip

• IgA Nephropathy and IgA Vasculitis (Henoch-Schönlein Purpura) are considered different clinical presentations of the same biological process. t
• IgA Nephropathy = Renal-limited form.
• IgA Vasculitis = Systemic form involving skin, joints, GI tract, and kidneys.

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Diagnostics

• Laboratory tests
  • Serum IgA level is elevated in 50% of patients.
  • Complement levels (e.g., C3 level) are generally normal.
    • Because IgA has weak complement-fixing activity. IgA is mainly in mucosa, where excessive inflammation needs to be avoided.

C3 levels help rule out poststreptococcal glomerulonephritis, membranoproliferative glomerulonephritis, and lupus nephritis.

• Renal biopsy
  • Light microscopy: mesangial proliferation
  • Immunofluorescent microscopy: mesangial IgA deposits
  • Electron microscopy: mesangial immune complex deposits

Differential diagnosis

Feature	IgA Nephropathy	PSGN
Onset	Days (1–3 days) after infection	Weeks (2–4 weeks) after infection
Timing Term	Synpharyngitic (Concurrent)	Post-infectious (Latent)
Serum C3	Normal	Low
Recurrence	Common (Episodic)	Rare
EM Site	Mesangial deposits	Subepithelial humps
IF Pattern	IgA-dominant	”Starry sky” / Granular (IgG, C3)
Prognosis	Variable (Chronic/ESRD risk)	Excellent (Spontaneous resolution)

Tip

1. IgA nephropathy typically occurs immediately following or during a mucosal infection (e.g., upper respiratory tract and gastrointestinal infections), not several weeks after a skin infection in PSGN.
2. Most patients also have flank pain and a low-grade fever, which are absent in PSGN.
3. Reoccurrence is common in IgA nephropathy, while it’s rare in PSGN.

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Treatment

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