What is the initial treatment approach for a patient diagnosed with IgA (Immunoglobulin A) Nephropathy?

Initial Treatment of IgA Nephropathy

Begin with optimized supportive care centered on ACE inhibitor or ARB therapy for all patients with proteinuria >0.5 g/day, regardless of blood pressure status, combined with strict blood pressure control and lifestyle modifications. 1

Step 1: Risk Assessment at Diagnosis

• Measure proteinuria, blood pressure, and eGFR at diagnosis and throughout follow-up to stratify progression risk 1
• Utilize the MEST-C histologic scoring system (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, crescents) on kidney biopsy 1
• Access the International IgAN Prediction Tool (Calculate by QxMD) for prognostic assessment, though this cannot predict treatment response 1
• Screen for secondary causes of IgAN before initiating therapy 1

Step 2: Foundational Supportive Care (All Patients)

Renin-Angiotensin System Blockade

• Initiate ACE inhibitor or ARB if proteinuria >0.5 g/day (Grade 1B recommendation), even in normotensive patients 1
• For proteinuria 0.5-1 g/day, ACE inhibitor or ARB is suggested (Grade 2D) 1
• Titrate upward to maximum tolerated dose targeting proteinuria <1 g/day 1, 2
• Do not use dual ACE inhibitor and ARB therapy due to lack of benefit and hyperkalemia risk 1

Blood Pressure Targets

• Target <130/80 mmHg for proteinuria <1 g/day 1, 2
• Target <125/75 mmHg for proteinuria ≥1 g/day 1, 2

Lifestyle and Cardiovascular Risk Management

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) 1
• Counsel on smoking cessation, weight control, and regular exercise 1
• Assess and manage cardiovascular risk factors aggressively 1
• No specific dietary interventions beyond sodium restriction have proven benefit 1

Emerging Supportive Therapies

• Consider adding SGLT2 inhibitors (dapagliflozin or empagliflozin) to ACE inhibitor/ARB therapy 1
• DAPA-CKD trial showed 36% reduction (HR 0.64) in 50% eGFR decline or kidney failure when dapagliflozin was added to RAS blockade in glomerulonephritis patients 1
• EMPA-KIDNEY included >800 IgAN patients with eGFR as low as 20 mL/min with favorable results 1

Step 3: Reassess After 90 Days of Optimized Supportive Care

If Proteinuria Remains >0.75-1 g/day:

The patient is at high risk for progressive CKD and requires consideration of immunosuppression or clinical trial enrollment 1

Step 4: Immunosuppressive Therapy (High-Risk Patients Only)

Glucocorticoid Therapy Criteria

• Consider 6-month course of glucocorticoids (Grade 2B) only if: 1
  • Proteinuria persists >0.75-1 g/day after ≥90 days optimized supportive care
  • eGFR ≥30 mL/min/1.73 m² (preferably ≥50 mL/min/1.73 m²)
  • No contraindications present

Absolute Contraindications to Glucocorticoids

Avoid glucocorticoids entirely or use extreme caution in: 1

• eGFR <30 mL/min/1.73 m²
• Diabetes mellitus
• Obesity (BMI >30 kg/m²)
• Latent infections (tuberculosis, hepatitis B/C, HIV)
• Secondary disease (liver cirrhosis)
• Active peptic ulceration
• Uncontrolled psychiatric disease
• Severe osteoporosis

Glucocorticoid Regimen (If Used)

• IV methylprednisolone 1g for 3 days at months 1,3, and 5, plus oral prednisone 0.5 mg/kg on alternate days for 6 months 2
• Recognize that clinical benefit is not definitively established and serious adverse events (particularly infections) are significant 1

Other Immunosuppressive Agents: Generally NOT Recommended

• Do not use cyclophosphamide or azathioprine combined with corticosteroids (except crescentic IgAN) 1, 2
• Do not use mycophenolate mofetil in non-Chinese patients 1, 2
• Do not use calcineurin inhibitors, rituximab, or antiplatelet agents 1
• Do not perform tonsillectomy in non-Japanese patients 1, 2

Alternative Consideration: Fish Oil

• May consider fish oil supplementation for persistent proteinuria >1 g/day despite optimized supportive care (Grade 2D) 1, 2

Step 5: Special Clinical Situations Requiring Modified Approach

IgAN with Minimal Change Disease Pattern

• Treat according to minimal change disease protocols with corticosteroids (Grade 2B) 1, 2
• This applies to nephrotic patients showing MCD histology with mesangial IgA deposits 1, 2

IgAN with Rapidly Progressive Glomerulonephritis (Crescentic IgAN)

• Define as >50% crescents on biopsy with rapid GFR decline 1, 2
• Treat with cyclophosphamide plus glucocorticoids using ANCA-vasculitis protocols (Grade 2D) 1, 2
• Note: Presence of crescents without GFR decline does not constitute rapidly progressive disease but requires close monitoring 1

IgAN with Acute Kidney Injury from Macroscopic Hematuria

• Provide supportive care for AKI 1
• Perform repeat kidney biopsy if no improvement within 2 weeks after hematuria cessation 1

Critical Pitfalls to Avoid

• Do not delay ACE inhibitor/ARB initiation in patients with proteinuria ≥0.5 g/day, even if normotensive 1
• Do not use immunosuppression as first-line therapy—always optimize supportive care for ≥90 days first 1
• Do not use glucocorticoids in patients with eGFR <30 mL/min/1.73 m² due to markedly increased adverse event risk 1
• Do not assume biopsy findings (MEST-C score, crescent number) predict treatment response—they only indicate prognosis 1
• Recognize that adverse effects from immunosuppression increase substantially as eGFR declines below 50 mL/min/1.73 m² 1

Treatment Goal

Target proteinuria reduction to <1 g/day, which serves as a surrogate marker for improved kidney outcomes regardless of how achieved 1, 2

Preferred Approach When Evidence is Uncertain

Strongly consider clinical trial enrollment for all high-risk patients before initiating glucocorticoids, given the uncertain benefit-to-risk ratio of current immunosuppressive options and multiple promising therapies under investigation (targeted-release budesonide, complement inhibitors, BAFF inhibitors, sparsentan) 1, 3