What is the diagnosis and treatment for a patient with suspected Berger's disease (IgA nephropathy)?

Berger's Disease (IgA Nephropathy): Diagnosis and Treatment

Diagnosis

Kidney biopsy is required for definitive diagnosis, demonstrating mesangial dominant or co-dominant IgA deposits on immunofluorescence. 1

Clinical Presentation to Recognize

• Episodic gross hematuria occurs in 40-50% of cases, characteristically following upper respiratory infections (synpharyngitic hematuria) 1
• Asymptomatic microscopic hematuria with proteinuria is the other common presentation 2, 1
• Family history of hematuria or renal failure may be present in isolated cases 1

When to Proceed with Kidney Biopsy

Proceed with kidney biopsy when persistent hematuria with proteinuria and concern for progressive kidney disease is present 1. The biopsy should be scored using the MEST-C histologic classification system to guide prognosis 3.

Essential Diagnostic Workup

• Exclude secondary causes in all biopsy-proven cases: systemic lupus erythematosus, liver disease, inflammatory bowel disease, and other conditions causing secondary IgA deposition 1
• Electron microscopy typically reveals electron-dense deposits in the mesangium, with C3 often co-deposited alongside IgA 1
• Assess prognosis using the International IgAN Prediction Tool 3

Critical Differential Diagnoses

• Thin basement membrane disease: gross hematuria in <10% of patients, positive family history of hematuria but typically negative family history of renal failure 1
• Alport syndrome: may have episodic gross hematuria with positive family history of renal failure; deafness may be present in X-linked inheritance 1

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Treatment Approach

All patients must receive optimized supportive care as first-line therapy, including RAS blockade, blood pressure control to 125/75 mmHg if proteinuria >1 g/day, and cardiovascular risk reduction. 3

First-Line: Optimized Supportive Care (ALL Patients)

• ACE inhibitor or ARB for all patients with proteinuria >0.5 g/day, regardless of hypertension status (Grade 1B) 3
• Blood pressure target of 125/75 mmHg in patients with proteinuria >1 g/day 3
• Cardiovascular risk reduction measures and weight control 3
• Continue supportive care for at least 90 days before considering immunosuppression 3

Second-Line: Glucocorticoids (High-Risk Patients Only)

Consider a 6-month course of glucocorticoids (Grade 2B) if proteinuria remains >0.75-1 g/day despite at least 90 days of optimized supportive care AND eGFR ≥30 ml/min/1.73 m². 3

Glucocorticoid Options

• Targeted-release budesonide is preferred for patients with UPCR >1.5 g/g, offering significant proteinuria reduction (34% at 9 months) with a more favorable safety profile than systemic corticosteroids 4
• Systemic corticosteroids (oral prednisone 1 mg/kg/day) can be used but carry significantly higher serious adverse events, including fatalities 4
• Maximum duration of systemic glucocorticoids should be 16 weeks at high dose, followed by taper to complete 6 months total 2

Budesonide-Specific Guidance

• FDA-approved indication: Primary IgA nephropathy with UPCR >1.5 g/g 4
• Contraindications: eGFR <30 ml/min/1.73m², uncontrolled diabetes, or inadequate trial of supportive care 4
• Monitoring: Target 50% reduction in proteinuria by 6 months and <1 g/day by 12 months; monitor proteinuria every 3 months and eGFR every 3-6 months 4

Special Clinical Scenarios

Rapidly Progressive IgAN (RPGN)

Treat with cyclophosphamide and glucocorticoids according to ANCA-associated vasculitis protocols when extensive crescent formation (>50% of glomeruli) is present with declining GFR 2, 3. This is the only indication for cyclophosphamide in IgAN 3.

Critical pitfall: The presence of crescents without concomitant GFR decline does NOT constitute rapidly progressive IgAN; these patients require close follow-up but not aggressive immunosuppression 2

AKI from Severe Visible Hematuria

• Focus on supportive care for AKI 2
• Consider repeat kidney biopsy if kidney function fails to improve within 2 weeks following cessation of hematuria 2

Nephrotic Syndrome in IgAN

• If coexistent minimal change disease features: treat according to MCD guidelines 2
• If coexistent mesangioproliferative GN: manage as high-risk IgAN 2

Population-Specific Considerations

• Chinese patients: Consider mycophenolate mofetil 1.5 g/day as a glucocorticoid-sparing agent for proteinuria >1 g/day with active histologic features 3, 4
• Japanese patients: May consider tonsillectomy 3
• Children: Strong evidence supports RAS blockade; immunosuppressants (particularly glucocorticoids) are used more widely, but trial-based evidence is absent 2

Therapies NOT Recommended

The following should NOT be used routinely in IgAN: azathioprine, cyclophosphamide (except rapidly progressive IgAN), calcineurin inhibitors, rituximab, mycophenolate mofetil (except Chinese patients), and tonsillectomy (except Japanese patients) 3.

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Treatment Goals and Monitoring

• Primary goal: Reduce proteinuria to <1 g/day as a surrogate marker of improved kidney outcome 3
• Monitor regularly: Proteinuria, blood pressure, and eGFR to assess response to therapy 3
• High-risk features at diagnosis: Proteinuria >1 g/day, hypertension, and impaired renal function predict disease progression 1