Latest KDIGO Guidelines for IgA Nephropathy Management (2021)
The cornerstone of IgA nephropathy (IgAN) management is optimized supportive care, with consideration of glucocorticoids only in high-risk patients with persistent proteinuria >1 g/day despite 3 months of maximal supportive therapy and eGFR ≥30 mL/min/1.73 m². 1
Initial Assessment and Risk Stratification
- Use clinical and histologic data to risk stratify patients
- Apply the International IgAN Prediction Tool to quantify progression risk
- Score kidney biopsy using the MEST-C classification
- Assess for variant forms of IgAN that require specific treatment:
- IgA deposition with minimal change disease
- IgAN with acute kidney injury
- IgAN with rapidly progressive glomerulonephritis
Optimized Supportive Care (First-Line for All Patients)
Blood Pressure Management
- Target BP <130/80 mmHg if proteinuria <1 g/day
- Target BP <125/75 mmHg if proteinuria ≥1 g/day 2
- Use ACEi or ARB at maximally tolerated doses for patients with proteinuria >0.5 g/day 1, 2
Lifestyle Modifications
- Dietary sodium restriction (<2.0 g/day) 1, 2
- Weight normalization for patients with obesity
- Smoking cessation
- Regular exercise as appropriate 2
- Limit dietary protein to 0.8-1 g/kg/day for patients with nephrotic-range proteinuria 1
Emerging Supportive Therapies
- SGLT2 inhibitors should be considered, particularly in patients with reduced eGFR 2, 3
- Sparsentan (dual endothelin-1 and angiotensin II receptor blocker) is an emerging option 4
Management Algorithm for High-Risk Patients
Step 1: Identify High-Risk Patients
- Persistent proteinuria >1 g/day despite 3 months of optimized supportive care
- eGFR ≥30 mL/min/1.73 m²
Step 2: Consider Glucocorticoid Therapy
- For patients with eGFR ≥30 mL/min/1.73 m²: Consider a 6-month course of glucocorticoids 1, 2
- Use with extreme caution or avoid entirely in patients with:
- eGFR <30 mL/min/1.73 m²
- Diabetes
- Obesity (BMI >30 kg/m²)
- Latent infections (e.g., viral hepatitis, tuberculosis)
- Secondary disease (e.g., liver cirrhosis)
- Active peptic ulceration
- Uncontrolled psychiatric disease
- Severe osteoporosis 1
Step 3: Population-Specific Considerations
- For Chinese patients: Consider mycophenolate mofetil as a glucocorticoid-sparing agent 1
- For Japanese patients: Consider tonsillectomy 1
Step 4: Special Situations
- For IgAN with rapidly progressive glomerulonephritis: Offer cyclophosphamide and glucocorticoids (similar to ANCA-associated vasculitis) 1
- For IgAN with minimal change disease: Treat according to minimal change disease guidelines 1
- For IgAN with AKI from severe visible hematuria: Focus on supportive care; consider repeat kidney biopsy if no improvement within 2 weeks after hematuria resolves 1
Treatments Not Recommended
- Azathioprine (except in rapidly progressive IgAN)
- Cyclophosphamide (except in rapidly progressive IgAN)
- Calcineurin inhibitors
- Rituximab
- Mycophenolate mofetil (except in Chinese patients)
- Tonsillectomy (except in Japanese patients) 1, 2
- Dual ACEI/ARB therapy (increased risk of hyperkalemia without additional benefit) 2
Monitoring and Follow-up
- Regularly assess proteinuria, targeting reduction to <1 g/day as a surrogate marker of improved kidney outcome 1, 2
- Monitor renal function (serum creatinine, eGFR), blood pressure, and hematuria
- Consider clinical trial enrollment when available 1
Emerging Therapies Under Evaluation
- Targeted-release budesonide
- Complement inhibitors (e.g., iptacopan)
- Therapies targeting B-cell development 1, 4, 5
Caution: The KDIGO 2021 guidelines represent the most current evidence-based recommendations, but several new therapies are emerging that may change the treatment landscape in the near future 4, 5.