What is the recommended management for a patient with biopsy‑proven IgA nephropathy who presents for follow‑up with normal serum creatinine and preserved renal function?

Management of Biopsy-Proven IgA Nephropathy with Normal Creatinine

For a patient with biopsy-proven IgA nephropathy presenting with normal serum creatinine, the cornerstone of management is optimized supportive care with RAS blockade (ACE inhibitors or ARBs), blood pressure control, and lifestyle modifications, with the decision to add immunosuppression based on the degree of proteinuria after at least 90 days of maximal supportive therapy. 1

Initial Risk Stratification

The critical first step is determining this patient's risk of progression by assessing three key parameters 2:

• Proteinuria level: This is the single most important predictor of outcome in IgA nephropathy 3
• Blood pressure control: Uncontrolled hypertension independently predicts adverse outcomes 3
• Pathological features: The MEST-C scoring system (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, crescents) provides independent prognostic information 1, 3

Key prognostic thresholds for proteinuria:

• Proteinuria >1 g/day = high risk for progression 2, 3
• Proteinuria 0.5-1 g/day = intermediate risk 2
• Proteinuria <0.5 g/day = low risk, excellent long-term prognosis 4

Research demonstrates that even proteinuria >0.3 g/day carries increased risk of creatinine doubling, though ESRD risk becomes significant only above 1 g/day 5.

First-Line Management: Optimized Supportive Care

All patients require comprehensive supportive care regardless of proteinuria level 1:

• RAS blockade: Initiate ACE inhibitor or ARB for proteinuria >0.5 g/day (Grade 1B recommendation) 2, 1

  • Uptitrate to maximum tolerated dose to achieve proteinuria <1 g/day 2
  • Even patients with proteinuria 0.5-1 g/day should receive RAS blockade 2

• Blood pressure targets 2:

  • <130/80 mmHg if proteinuria <1 g/day
  • <125/75 mmHg if proteinuria >1 g/day

• Lifestyle modifications 1:

  • Sodium restriction to <2.0 g/day (<90 mmol/day)
  • Cardiovascular risk reduction (consider statin for any proteinuria >0.5 g/day) 3
  • Pneumococcal and influenza vaccination 1

This supportive care phase must continue for at least 90 days before considering immunosuppression 1.

Decision Point: When to Add Immunosuppression

After 90 days of optimized supportive care, reassess proteinuria 1:

If proteinuria remains >0.75-1 g/day:

• Consider 6-month course of glucocorticoid therapy (Grade 2B) 1
• Alternative: Enrollment in clinical trial 1
• Target: Reduce proteinuria to <1 g/day 1, 3

If proteinuria <0.75 g/day:

• Continue supportive care only 1
• Long-term prognosis is excellent with conservative management alone 4

Special consideration for rapidly progressive disease:

• If >50% crescents on biopsy with rapidly deteriorating kidney function, treat with cyclophosphamide and glucocorticoids following ANCA-vasculitis protocols 1

Therapies NOT Recommended for Standard IgA Nephropathy

Avoid these agents in routine management 1:

• Azathioprine
• Cyclophosphamide (except rapidly progressive IgAN)
• Calcineurin inhibitors
• Rituximab

Monitoring Strategy

Regular follow-up should assess 2, 1:

• Proteinuria: Primary surrogate marker of treatment response 1
• eGFR trajectory: A 40% decline over 2-3 years indicates poor outcome 1
• Blood pressure control: Maintain target based on proteinuria level 2

Research shows that achieving complete remission (proteinuria reduction) is critical—patients without remission have significantly worse outcomes 6. Even in patients achieving clinical remission of proteinuria, pathological activity may persist on repeat biopsy, suggesting continued vigilance is warranted 7.

Critical Pitfalls to Avoid

Do not delay RAS blockade 2, 1: Even minimal proteinuria (0.5-1 g/day) warrants treatment, as this represents a critical threshold for progression risk 5.

Do not rush to immunosuppression 1: The 90-day observation period on maximal supportive care is essential, as many patients achieve spontaneous remission, particularly those with preserved kidney function 6.

Do not ignore cardiovascular risk 3: Sub-nephrotic proteinuria independently increases cardiovascular complications, warranting aggressive risk factor modification even when renal function is stable.

Do not assume normal creatinine equals low risk 5, 4: Proteinuria level, not creatinine, drives long-term prognosis in IgA nephropathy.