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

EP: 1.Advancing IgA Nephropathy Care: Emerging Therapies, Unmet Needs, and Economic Considerations

EP: 2.Introduction to IgA Nephropathy

EP: 3.Pathogenesis of IgA Nephropathy: The 4-Hit Cascade, A Proliferation-Inducing Ligand (APRIL), and cytokines

EP: 4.Diagnosing IgA Nephropathy

EP: 5.Signs and Symptoms of IgA Nephropathy

EP: 6.Challenges in Timely Identification of IgA Nephropathy

EP: 7.Clinical Impact of IgA Nephropathy and Quality of Life

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EP: 8.Overview of Treatment Landscape for IgA Nephropathy: Standard of Care and KDIGO Guidelines

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.