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IgA nephropathy (IgAN), also known as Berger’s disease

IgA nephropathy (IgAN), also known as Berger’s disease, is a common glomerular disease characterized by IgA immune complex deposition in the mesangium of the kidneys, leading to inflammation and potential progression to chronic kidney disease (CKD). Below is a concise overview of IgAN, covering its pathophysiology, clinical features, diagnosis, and management. Pathophysiology Clinical Features Diagnosis…

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IgA nephropathy (IgAN), also known as Berger’s disease, is a common glomerular disease characterized by IgA immune complex deposition in the mesangium of the kidneys, leading to inflammation and potential progression to chronic kidney disease (CKD). Below is a concise overview of IgAN, covering its pathophysiology, clinical features, diagnosis, and management.

Pathophysiology

  • Mechanism:
    • IgA1 deposition: Abnormal galactose-deficient IgA1 (Gd-IgA1) forms immune complexes that deposit in the renal mesangium.
    • These complexes trigger mesangial cell proliferation, matrix expansion, and inflammation, causing glomerular injury.
  • Triggers:
    • Often associated with mucosal infections (e.g., upper respiratory or gastrointestinal), as IgA is produced at mucosal surfaces.
    • Genetic predisposition (e.g., familial clustering in some populations).
  • Progression:
    • Varies widely; some patients remain stable, while others progress to CKD or end-stage renal disease (ESRD) due to glomerulosclerosis and tubulointerstitial fibrosis.

Clinical Features

  • Common Presentations:
    • Macroscopic Hematuria: Visible blood in urine, often triggered by infections (e.g., pharyngitis, “synpharyngitic hematuria”).
    • Microscopic Hematuria: Persistent, detected on urinalysis.
    • Proteinuria: Mild to moderate (<3.5 g/day); nephrotic-range proteinuria is rare.
    • Hypertension: Common, especially with progressive disease.
    • Asymptomatic: Often detected incidentally on routine urinalysis.
  • Rare Features:
    • Acute kidney injury (AKI): Due to crescentic IgAN or heavy hematuria.
    • Nephrotic syndrome: If significant glomerular damage.
  • Epidemiology:
    • Most common in young adults (20–40 years), males > females.
    • Higher prevalence in Asia (e.g., Japan, China) and Europe; less common in African populations.

Diagnosis

  1. Clinical Suspicion:
    • Macroscopic hematuria post-infection, persistent microscopic hematuria, or proteinuria in a young adult.
    • Family history or associated conditions (e.g., Henoch-Schönlein purpura/IgA vasculitis).
  2. Laboratory Findings:
    • Urinalysis:
      • Hematuria (RBCs, dysmorphic RBCs indicating glomerular origin).
      • Proteinuria (mild to moderate, <3 g/day).
    • Serum Creatinine: Normal early; elevated in advanced disease.
    • Serum IgA: Elevated in ~30–50% of cases but not specific.
    • Complement Levels: Normal (unlike lupus nephritis or post-infectious glomerulonephritis).
  3. Kidney Biopsy (Gold Standard):
    • Light Microscopy: Mesangial proliferation, matrix expansion; crescents in severe cases.
    • Immunofluorescence: Dominant or co-dominant IgA deposits in the mesangium; may include C3, IgG, or IgM.
    • Electron Microscopy: Mesangial electron-dense deposits.
    • Oxford MEST-C Score: Classifies biopsy findings (Mesangial hypercellularity, Endocapillary proliferation, Segmental sclerosis, Tubular atrophy, Crescents) to predict prognosis.
  4. Differential Diagnosis:
    • Post-infectious glomerulonephritis: Low C3, recent streptococcal infection.
    • Lupus nephritis: Positive ANA, low C3/C4.
    • Henoch-Schönlein purpura: IgAN with systemic vasculitis (purpura, arthritis).
    • Thin basement membrane disease: Hematuria without proteinuria or IgA deposits.
    • Alport syndrome: Hematuria with hearing loss, family history.

Management

  1. General Measures:
    • Blood Pressure Control:
      • Target <130/80 mmHg (or <125/75 mmHg if proteinuria >1 g/day).
      • ACE Inhibitors (ACEi) or Angiotensin Receptor Blockers (ARBs): Reduce proteinuria and slow disease progression.
    • Lifestyle:
      • Low-sodium diet, smoking cessation, weight management.
      • Avoid NSAIDs (worsen renal function).
    • Monitor: Regular urinalysis, proteinuria (spot urine protein/creatinine ratio), serum creatinine, eGFR.
  2. Risk Stratification:
    • Low Risk: Minimal proteinuria (<0.5 g/day), normal eGFR, no hypertension.
      • Observation and supportive care.
    • Moderate to High Risk: Proteinuria >1 g/day, declining eGFR, hypertension, or adverse biopsy features (e.g., high MEST-C score).
      • Consider additional therapies.
  3. Immunosuppression (Controversial):
    • Indications: High-risk features (e.g., proteinuria >1 g/day despite 6 months of optimized ACEi/ARB, crescentic IgAN, rapidly declining eGFR).
    • Corticosteroids:
      • High-dose prednisone (e.g., 0.5–1 mg/kg/day, tapered over 6 months).
      • Supported by trials like TESTING (reduced proteinuria but infection risk).
    • Other Agents:
      • Cyclophosphamide or mycophenolate mofetil (MMF) for crescentic IgAN or refractory cases.
      • Limited evidence for azathioprine or rituximab.
    • Risks: Immunosuppression may not benefit all patients and increases infection, malignancy risk.
  4. Emerging Therapies:
    • Sparsentan: Dual endothelin/angiotensin receptor antagonist; reduces proteinuria (under investigation).
    • SGLT2 Inhibitors (e.g., Dapagliflozin): Slow CKD progression; shown benefit in IgAN (DAPA-CKD trial).
    • Complement Inhibitors: Targeting complement activation (e.g., anti-C5a or MASP-2 inhibitors) in trials.
    • Budesonide (Nefecon): Targeted-release oral budesonide; reduces proteinuria by stabilizing mucosal IgA production; approved in some regions.
  5. Management of Complications:
    • AKI: Supportive care; dialysis if severe.
    • ESRD: Dialysis or kidney transplant (IgAN may recur in 20–40% of grafts but rarely causes graft loss).

Prognosis

  • Variable:
    • ~20–40% progress to ESRD within 20 years.
    • Poor prognostic factors: Proteinuria >1 g/day, hypertension, reduced eGFR, adverse biopsy findings (e.g., tubular atrophy, crescents).
  • Good Prognosis: Patients with isolated hematuria or minimal proteinuria often remain stable.
  • Monitoring: Lifelong follow-up due to risk of slow progression.

Key Points

  • IgA Nephropathy: Common glomerular disease with IgA mesangial deposits, triggered by mucosal infections or genetic factors.
  • Presentation: Macro/microscopic hematuria, proteinuria, hypertension; often asymptomatic.
  • Diagnosis: Kidney biopsy with IgA-dominant mesangial deposits; supported by urinalysis and normal complement.
  • Management: ACEi/ARBs for proteinuria and BP control; corticosteroids or emerging therapies (e.g., budesonide, SGLT2i) for high-risk cases.
  • Prognosis: Variable; 20–40% reach ESRD in 20 years; regular monitoring is critical.

Disclaimer: Grok is not a doctor; please consult one.

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