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
- 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).
- 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).
- Urinalysis:
- 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.
- 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
- 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.
- Blood Pressure Control:
- 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.
- Low Risk: Minimal proteinuria (<0.5 g/day), normal eGFR, no hypertension.
- 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.
- 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.
- 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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