IgA Glomerulonephritis Workup and Treatment
Initial Diagnostic Workup
All patients with suspected IgA nephropathy require kidney biopsy for definitive diagnosis, which demonstrates dominant mesangial IgA1 deposition. 1
Essential Baseline Assessments
- Measure 24-hour urine protein or spot urine protein-to-creatinine ratio to quantify proteinuria, as this is the primary driver of treatment decisions 1
- Obtain serum creatinine and calculate eGFR to assess kidney function and determine eligibility for immunosuppression 1
- Measure blood pressure at every visit, as hypertension is both a risk factor and treatment target 2
- Document presence of hematuria (microscopic or macroscopic) as part of the clinical phenotype 2
- Check serum IgA levels, though elevated in only 50% of cases and not required for diagnosis 3
Risk Stratification Using Biopsy
- Request Oxford MEST scoring (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis) as it provides independent prognostic information 4
- Quantify percentage of crescents to identify rapidly progressive disease requiring aggressive immunosuppression 4
- Assess for minimal change disease pattern with foot process effacement, as this requires different treatment 4
Treatment Algorithm
Step 1: Optimize Supportive Care (ALL Patients)
Begin ACE inhibitor or ARB therapy immediately for any patient with proteinuria ≥0.5 g/day, titrating upward as tolerated to achieve proteinuria <1 g/day. 1, 5
Blood Pressure Targets
Duration Before Escalation
- Continue optimized supportive care for 3-6 months before considering immunosuppression 4, 1
- Monitor proteinuria every 3 months during this period to assess response 6
Step 2: Add Immunosuppression (Select Patients)
For patients with persistent proteinuria ≥1 g/day after 3-6 months of optimized supportive care AND eGFR >50 ml/min/1.73m², initiate a 6-month course of corticosteroid therapy. 4, 1, 5
Corticosteroid Regimens (Choose One)
Pozzi Protocol (preferred based on long-term outcome data): 6
- IV methylprednisolone 1g for 3 consecutive days at months 1,3, and 5
- PLUS oral prednisone 0.5 mg/kg on alternate days for 6 months
- This regimen achieved 97% 10-year renal survival versus 53% in controls 6
Alternative Oral Regimen: 5
- Oral prednisone 0.8-1 mg/kg/day for 2 months
- Then reduce by 0.2 mg/kg/day per month for the next 4 months
Contraindications to Corticosteroids
- eGFR <30 ml/min/1.73m² (unless crescentic disease present) 4, 5
- Uncontrolled diabetes or metabolic syndrome 6
- Advanced age with frailty 6
- Obesity 6
- Active or latent infections 6
Step 3: Adjunctive Therapies
Consider adding fish oil for patients with persistent proteinuria ≥1 g/day despite optimized supportive care. 4, 1, 5
Special Clinical Scenarios
Crescentic IgA Nephropathy (Rapidly Progressive)
Define as >50% crescents on biopsy with rapidly progressive renal deterioration. 4
Treat with steroids plus cyclophosphamide analogous to ANCA vasculitis, regardless of baseline eGFR. 4
- This is the ONLY indication for cyclophosphamide in IgAN 4, 5
- Consider treatment even if crescents approach 50% due to potential sampling error 4
Minimal Change Disease Pattern with IgA Deposits
Treat as minimal change disease in nephrotic patients showing minimal light microscopic changes with mesangial IgA deposits. 4
- Look for diffuse foot-process effacement on electron microscopy 4
- Use high-dose corticosteroids as for primary MCD 4
Acute Kidney Injury with Macroscopic Hematuria
Provide general supportive care if biopsy shows only acute tubular necrosis and intratubular erythrocyte casts. 4
Consider repeat biopsy after 5 days if no improvement to exclude crescentic disease, though timing should be individualized based on clinical context 4
- AKI typically results from tubular obstruction by erythrocyte casts 4
- If previous episodes resolved spontaneously, repeat biopsy may not be needed 4
Therapies to AVOID
Do NOT Use (Strong Evidence Against)
- Corticosteroids combined with cyclophosphamide or azathioprine (except crescentic disease) 4, 5
- Mycophenolate mofetil (MMF) - no benefit demonstrated in Belgian and American trials 4, 5
- Antiplatelet agents (dipyridamole) - low-quality evidence and poor adherence 4
- Routine tonsillectomy - not recommended unless recurrent tonsillitis with macroscopic hematuria 4
- Immunosuppression if eGFR <30 ml/min/1.73m² (except crescentic disease) 4, 5
Monitoring During Treatment
Proteinuria Assessment
- Check every 3 months during and after treatment 6
- Goal is reduction to <1 g/day, which predicts favorable long-term outcomes regardless of how achieved 4, 1, 5
Kidney Function
- Monitor eGFR every 3-6 months to assess disease trajectory 6
Steroid-Related Complications
- Screen for glucose intolerance 5
- Monitor blood pressure (may worsen on steroids) 5
- Assess infection risk 6, 5
- Monitor weight gain 6
Critical Pitfalls to Avoid
- Do not delay ACE inhibitor/ARB initiation - start immediately when proteinuria ≥0.5 g/day 1
- Do not use corticosteroids in patients with eGFR <50 ml/min/1.73m² unless crescentic disease 4, 1
- Do not assume all IgAN is the same - Asian populations show more severe presentation and active lesions than Europeans 7
- Do not treat proteinuria <1 g/day with immunosuppression - supportive care alone is sufficient 2
- Do not use MMF based on older literature - recent high-quality trials show no benefit 4, 5