IgA nephropathy

IgA nephropathy (Berger disease) is the most common primary glomerulonephritis worldwide. It most frequently affects males in the second to third decades of life. Clinical manifestations are usually triggered by upper respiratory tract or gastrointestinal infections and include gross hematuria and flank pain. In some cases, it may present as rapidly progressive glomerulonephritis (RPGN). Urinalysis of asymptomatic patients often shows persistent microhematuria and minor proteinuria, while more severe cases may manifest with recurrent episodes of nephritic syndrome. A kidney biopsy is indicated in patients with signs of severe or progressive disease to make a definitive diagnosis. Treatment consists of measures to slow the progression of the disease (e.g., ACE inhibitors) as well as immunosuppressive therapy in more severe cases. Even with the appropriate treatment, up to 50% of patients progress to end-stage renal disease within 20–25 years.

IgA nephropathy is the most common primary glomerulonephritis in adults. ^[1]

• Peak incidence: second to third decades of life ^[2]
• Sex: ♂ > ♀ (2:1) ^[3]
• Ethnicity: more common in the Asian population (worldwide) ^[4]

Epidemiological data refers to the US, unless otherwise specified.

• The cause is still not entirely understood.
• Most likely mechanism: 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) ^[5]

The course of the disease is highly variable and can manifest in the following forms:

• Asymptomatic
• 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 ^[6]
• 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.

IgA nephropathy and IgA vasculitis are both IgA-mediated vasculitides triggered by a mucosal infection. IgA vasculitis most commonly occurs in children < 10 years of age and affects multiple organ systems (palpable purpura, abdominal pain, arthralgia). IgA nephropathy is limited to the kidneys and typically affects adults.

References:^{[6][7][8][9][10][11]}

Diagnosis is based on clinical presentation and laboratory results. In some cases, renal biopsy may be indicated to confirm the diagnosis.

• Urinalysis
  • Signs of nephritic sediment, including persistent microhematuria and possibly minor proteinuria
  • Episodic flare-ups of gross hematuria in 50% of patients ^[7]
  • In rare cases, nephrotic sediment
• Laboratory tests
  • Serum IgA level is elevated in 50% of patients.
  • Complement levels (e.g., C3 level) are generally normal. ^[12]
• Renal biopsy
  • Usually only indicated if there are signs of severe or progressive disease, including:
    • Urinary protein > 0.5–1 g/24 h
    • ↑ Serum creatinine
    • Hypertension
  • Findings
    • Light microscopy: mesangial proliferation
    • Immunofluorescent microscopy: mesangial IgA deposits
    • Electron microscopy: mesangial immune complex deposits

The renal manifestation of IgA vasculitis is pathologically the same as IgA nephropathy.

• Poststreptococcal glomerulonephritis
  • Associated with low complement levels
  • Typically occurs 10–20 days following an infection
• Lupus nephritis
• Membranoproliferative glomerulonephritis

The differential diagnoses listed here are not exhaustive.

• Patients with isolated hematuria
  • Regularly monitor kidney function and initiate treatment if disease progresses (e.g., occurrence of proteinuria).
  • Symptoms resolve spontaneously in 30% of patients.
• Patients with proteinuria or hypertension: ACE inhibitors/angiotensin II receptor blockers
• For severe/rapidly progressive disease: glucocorticoids PLUS possibly cyclophosphamide/azathioprine