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Overview of Treatment Landscape for IgA Nephropathy: Standard of Care and KDIGO Guidelines

Panelists discuss how immunoglobulin A (IgA) nephropathy treatment has evolved to include supportive care with optimized blood pressure control and renin-angiotensin system blockade as first-line therapy, with increasingly targeted immunomodulatory approaches for higher-risk patients showing persistent proteinuria.

Treatment Landscape and Standard of Care for IgA Nephropathy

Current Treatment Approach

The management of IgA nephropathy (IgAN) follows a risk-stratified approach with treatment intensity tailored to disease severity and progression risk:

Supportive Care (All Patients)

  • Renin-angiotensin-aldosterone system (RAAS) blockade: Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) titrated to maximum tolerated dose, particularly in patients with proteinuria > 0.5 g/day
  • Blood pressure control: Target < 130/80 mmHg
  • Lifestyle modifications: Sodium restriction, weight management, smoking cessation, and physical activity
  • Cardiovascular risk management: Lipid control, glycemic management in diabetics

Disease-Specific Therapies (Risk-Based)

  • Corticosteroids: For patients with persistent proteinuria > 1g/day despite 3-6 months of optimized supportive care
  • Immunosuppressive agents: Cyclophosphamide, mycophenolate mofetil, or rituximab for rapidly progressive disease or crescentic IgAN
  • Tonsillectomy: Considered in select patients, particularly in populations with high prevalence of tonsillitis-associated hematuria
  • Fish oil supplements: May provide modest benefit in some patients, though evidence remains inconsistent

Emerging Therapies

  • Targeted complement inhibition: Targeting alternative complement pathway
  • Targeted B-cell therapies: Addressing aberrant IgA1 production
  • SGLT2 inhibitors: Showing renoprotective effects in proteinuric kidney diseases

Key Points From KDIGO Guidelines

  1. Risk assessment:
    1. Recommend comprehensive assessment of proteinuria, blood pressure, estimated glomerular filtration rate (eGFR), and histopathological features (MEST-C score)
    2. Identify high-risk patients: persistent proteinuria > 1g/day, declining eGFR, hypertension, and adverse histology
  2. Initial management:
    1. Maximize RAAS blockade as first-line therapy for all patients with proteinuria > 0.5g/day
    2. Optimize supportive care for 3-6 months before considering immunosuppression
  3. Immunosuppressive therapy:
    1. Consider corticosteroids for patients with persistent proteinuria > 1g/day despite optimal supportive care
    2. Recommend caution with immunosuppression in patients with eGFR < 30 mL/min/1.73m²
    3. Balance potential benefits against risks of therapy
  4. Special populations:
    1. Crescentic IgAN (> 50% crescents): Consider cyclophosphamide and corticosteroids
    2. Nephrotic syndrome: Evaluate for minimal change disease overlap
    3. Pregnancy: Continue ACE/ARB until conception planning, then switch to alternative antihypertensives
  5. Monitoring:
    1. Regular assessment of proteinuria, eGFR, and blood pressure every 3-6 months
    2. Consider repeat biopsy in cases of unexpected disease course
  6. End-stage kidney disease management:
    1. Transplantation is preferred over dialysis when feasible
    2. Acknowledge risk of recurrence posttransplant (30%-35%)
  7. Research priorities:
    1. Emphasize need for biomarkers to guide therapy
    2. Support development of targeted therapies addressing disease pathogenesis

The guidelines emphasize a personalized approach, balancing risk of progression against potential treatment toxicities, with treatment decisions made in the context of patient preferences and values.

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