Treatment of IgA Nephropathy
All patients with IgA nephropathy should receive optimized supportive care as first-line therapy, consisting of ACE inhibitor or ARB therapy for proteinuria >0.5 g/day, blood pressure control, and cardiovascular risk reduction, with glucocorticoids reserved only for high-risk patients who maintain proteinuria >0.75-1 g/day despite at least 90 days of maximal supportive care and have eGFR ≥30 ml/min/1.73 m². 1
Initial Management: Optimized Supportive Care
Blood Pressure and RAS Blockade
- Initiate ACE inhibitor or ARB therapy for all patients with proteinuria >0.5 g/day, regardless of whether hypertension is present (Grade 1B). 1
- Target blood pressure <130/80 mmHg for proteinuria <1 g/day, and <125/75 mmHg when proteinuria is >1 g/day. 1
- Uptitrate ACE inhibitor or ARB to maximally tolerated doses to achieve proteinuria <1 g/day. 1
- Do not use dual ACE inhibitor and ARB therapy due to lack of additional benefit and increased risk of hyperkalemia. 1
Cardiovascular Risk and Lifestyle Modifications
- Assess and manage cardiovascular risk factors aggressively. 1
- Implement dietary sodium restriction (the only dietary intervention with proven benefit). 1
- Counsel on smoking cessation, weight control, and regular exercise. 1
Emerging Supportive Therapies
- Consider adding SGLT2 inhibitors to ACE inhibitor/ARB therapy, as trials like DAPA-CKD showed 36% reduction in composite kidney outcomes (HR 0.64) in glomerulonephritis patients, including IgA nephropathy. 1
Risk Stratification
Prognostic Assessment
- Use the International IgAN Prediction Tool to quantify progression risk and guide shared decision-making, incorporating clinical data at biopsy (eGFR, proteinuria) and MEST-C histologic scoring. 1
- High-risk features include: proteinuria >0.75-1 g/day persisting after 3-6 months of optimized supportive care, eGFR decline, or high-risk MEST-C scores. 1
Immunosuppressive Therapy for High-Risk Patients
Glucocorticoid Therapy Criteria
Consider a 6-month course of glucocorticoids (Grade 2B) only if ALL of the following are met: 1
- Proteinuria remains >0.75-1 g/day despite at least 90 days (3 months) of optimized supportive care
- eGFR ≥30 ml/min/1.73 m²
- No contraindications to glucocorticoid therapy
Glucocorticoid Toxicity Risk Stratification
Exercise extreme caution or avoid glucocorticoids entirely in patients with: 1
- eGFR <50 ml/min/1.73 m² (markedly increased adverse event risk)
- Advanced age
- Metabolic syndrome or obesity
- Diabetes mellitus
- Latent infections (tuberculosis, HIV, hepatitis B or C)
Glucocorticoid Regimen and Prophylaxis
- When using glucocorticoids at doses ≥0.5 mg/kg/day prednisone equivalent, mandatory prophylaxis includes: 1
- Pneumocystis jirovecii pneumonia prophylaxis
- Gastroprotection
- Bone protection per local guidelines
Evidence Limitations
- The TESTING trial showed kidney outcome benefits but was terminated early due to serious adverse events (predominantly infections) in the glucocorticoid group, with 4 fatalities despite prophylaxis. 1
- Clinical benefit of glucocorticoids in IgA nephropathy is not definitively established, and the risk-benefit profile must be individually discussed with each patient. 1
Alternative and Emerging Therapies
FDA-Approved Targeted Therapy
- Enteric-coated budesonide (nefecon) received FDA accelerated approval in December 2021 for primary IgA nephropathy with UPCR >1.5 g/g, showing 34% reduction in proteinuria at 9 months. 1
Population-Specific Considerations
- Chinese patients: Consider mycophenolate mofetil as a glucocorticoid-sparing agent. 1
- Japanese patients: Consider tonsillectomy. 1
Therapies NOT Recommended
Do not use the following for routine IgA nephropathy management: 1
- Mycophenolate mofetil (except in Chinese patients)
- Azathioprine
- Cyclophosphamide (except for rapidly progressive IgAN)
- Calcineurin inhibitors
- Rituximab
- Antiplatelet agents
- Fish oil (insufficient evidence despite prior suggestions)
- Tonsillectomy (except in Japanese patients)
Special Clinical Scenarios
Rapidly Progressive IgA Nephropathy
Treat with cyclophosphamide and glucocorticoids (analogous to ANCA-associated vasculitis) if: 1
- Extensive crescent formation (>50% of glomeruli) on kidney biopsy
- Rapidly declining GFR
- This represents true RPGN, not merely the presence of crescents without GFR decline
IgA Nephropathy with Minimal Change Disease
- Treat according to minimal change disease protocols with glucocorticoids. 1
Acute Kidney Injury from Macroscopic Hematuria
- Provide supportive care for AKI. 1
- Consider repeat kidney biopsy if no improvement in kidney function within 2 weeks after hematuria cessation. 1
Treatment Goals and Monitoring
Target Proteinuria
- Aim for proteinuria <1 g/day as a surrogate marker for improved kidney outcomes. 2
- Each 10% decrease in time-averaged proteinuria from baseline is associated with an 11% reduction in kidney failure/death risk (HR 0.89). 3
Monitoring Parameters
- Monitor proteinuria, blood pressure, and eGFR regularly to assess treatment response. 2
- Patients with eGFR loss >1 ml/min/1.73 m²/year are at high risk for progression to kidney failure within their lifetime. 3
Critical Clinical Pitfalls
Common Errors to Avoid
- Do not delay ACE inhibitor/ARB therapy until proteinuria reaches 1 g/day; the threshold is now 0.5 g/day. 1
- Do not use glucocorticoids in patients with eGFR <30 ml/min/1.73 m² unless rapidly progressive crescentic disease is present. 1
- Do not assume low proteinuria (<0.88 g/g) means low risk; 20% of these patients develop kidney failure within 10 years. 3
- Do not use the International IgAN Prediction Tool to monitor treatment response; it is only valid at diagnosis. 1