Opinion
Video
Sequencing and Individualizing Treatments for IgA Nephropathy
Panelists discuss how treatment sequencing in immunoglobulin A (IgA) nephropathy will likely evolve toward a risk-stratified approach, beginning with optimized supportive care and renin-angiotensin system blockade, then incorporating targeted therapies based on specific disease mechanisms and biomarker profiles before resorting to broader immunosuppression.
Evolution of Treatment Sequencing in IgA Nephropathy
Emerging Risk-Stratified Treatment Paradigm
The approach to IgA nephropathy management is evolving from a one-size-fits-all model to a personalized, risk-stratified framework:
Foundation Therapy (All Patients)
- Optimized supportive care: Maximal tolerated renin-angiotensin-aldosterone system blockade remains the cornerstone for all patients
- SGLT2 inhibition: Increasingly incorporated as standard foundation therapy regardless of risk category
- Comprehensive risk factor management: Blood pressure control, metabolic management, and lifestyle optimization
Risk-Based Treatment Escalation
Low-Risk Patients
- Defining characteristics: Proteinuria < 1g/day, stable estimated glomerular filtration rate (eGFR), minimal histological activity
- Approach: Foundation therapy with surveillance
- Monitoring focus: Detection of disease progression requiring therapy escalation
Moderate-Risk Patients
- Defining characteristics: Persistent proteinuria 1-3 g/day despite supportive care, mild eGFR decline
- First escalation: Targeted therapies addressing specific disease mechanisms
- APRIL/BAFF pathway inhibitors for patients with elevated galactose-deficient IgA1 (Gd-IgA1)
- Complement-targeted therapies for those with complement activation biomarkers
- Sequencing principle: Mechanism-specific targeted therapy before broader immunosuppression
High-Risk Patients
- Defining characteristics: Nephrotic-range proteinuria, rapid eGFR decline, crescentic features
- Approach: More aggressive initial therapy, potentially combining:
- Short-course corticosteroids for rapid anti-inflammatory effect
- Targeted therapy for long-term disease modification
- Consideration of multitargeted approaches addressing multiple pathogenic pathways
Biomarker-Guided Sequential Therapy
- Initial biomarker assessment: Evaluation of Gd-IgA1 levels, autoantibodies, complement markers
- Dynamic reassessment: Periodic biomarker monitoring to guide subsequent therapeutic decisions
- Response-based adjustment: Sequential therapy modification based on the following:
- Proteinuria reduction thresholds
- eGFR trajectory stabilization
- Biomarker normalization
- Patient-reported outcomes
This evolving approach represents a significant advancement from traditional protocols, emphasizing precision medicine principles and mechanism-based therapeutic selection rather than uniform treatment escalation.
