Glucocorticoid Treatment for IgA Nephropathy
Glucocorticoids should be reserved for high-risk IgA nephropathy patients with persistent proteinuria ≥0.75-1 g/day despite at least 90 days of optimized supportive care (RAS blockade and blood pressure control), and only when eGFR remains ≥30 ml/min/1.73 m². 1
Primary Treatment Foundation
Before considering glucocorticoids, all patients must receive optimized supportive care as the cornerstone of management 1, 2:
- RAS blockade (ACE inhibitors or ARBs) for all patients with proteinuria >0.5 g/day, regardless of hypertension status 1, 2
- Blood pressure targets: <130/80 mmHg for proteinuria <1 g/day; <125/75 mmHg for proteinuria >1 g/day 3, 2
- Cardiovascular risk reduction and weight control 1
This supportive care phase must continue for at least 3-6 months before escalating to immunosuppression 3, 1.
When to Use Glucocorticoids
Indications (Grade 2B-2C evidence)
Glucocorticoids are appropriate when ALL of the following criteria are met 3, 1:
- Proteinuria persists ≥0.75-1 g/day after 90 days of optimized supportive care
- eGFR ≥30 ml/min/1.73 m² (some guidelines suggest ≥50 ml/min/1.73 m²) 3
- No absolute contraindications (see below)
The 2023 KDOQI commentary emphasizes that while the TESTING trial showed reduced composite kidney outcomes with steroids, serious adverse events remained significantly higher, including 4 fatalities despite pneumocystis prophylaxis 3. The STOP-IgAN trial demonstrated proteinuria reduction but no sustained legacy effect after treatment discontinuation 3.
Glucocorticoid Regimen
- Oral prednisone/prednisolone dosing varies by protocol
- Alternative: Methylprednisolone pulse therapy has been used in patients with impaired renal function 4
Emerging alternative: Enteric-coated budesonide received FDA accelerated approval in December 2021 for primary IgA nephropathy with UPCR >1.5 g/g, showing 34% proteinuria reduction at 9 months with potentially fewer systemic adverse effects 3, 1.
Relative Contraindications to Steroids
Carefully weigh risks in patients with 3:
- Obesity
- Glucose intolerance or diabetes
- Poorly controlled hypertension
- History of serious infections
- Osteoporosis
The Canadian Society of Nephrology emphasizes that potential benefits must be evaluated at the individual patient level, considering these contraindications 3.
Special Populations Requiring Different Approaches
Rapidly Progressive/Crescentic IgA Nephropathy
For patients with >50% crescents and rapidly declining GFR, use aggressive immunosuppression analogous to ANCA vasculitis 3, 1:
- Combination of glucocorticoids plus cyclophosphamide 3, 1
- This is the ONLY indication for cyclophosphamide in IgA nephropathy 2
Nephrotic Syndrome with Minimal Change Features
Treat as minimal change disease when biopsy shows minimal change pathology with mesangial IgA deposits 3.
Chinese Patients
Mycophenolate mofetil (MMF) 1.5 g/day combined with lower-dose prednisone (0.4-0.6 mg/kg/day) may be considered as a glucocorticoid-sparing alternative in Chinese patients with high proteinuria and active histologic features 3, 1.
Monitoring and Treatment Goals
Target proteinuria reduction 1, 2:
- 25% reduction by 3 months
- 50% reduction by 6 months
- <1 g/day by 12 months (complete clinical response)
Do not assume treatment failure prematurely—response assessment does not require a full 6-month trial before determining if the patient will benefit 3. However, proteinuria frequently recurs after corticosteroid cessation 3.
Therapies NOT Recommended
The following should be avoided in routine IgA nephropathy management 1, 2:
- Azathioprine (except after cyclophosphamide in crescentic disease)
- Cyclophosphamide (except rapidly progressive disease)
- Calcineurin inhibitors
- Rituximab
- MMF (except possibly in Chinese patients)
- Fish oil (no longer recommended per updated guidelines) 3
Critical Pitfalls to Avoid
Starting glucocorticoids without adequate supportive care trial: Always optimize RAS blockade and blood pressure control for 3-6 months first 1, 2
Using steroids in advanced CKD: Do not use immunosuppression when eGFR <30 ml/min/1.73 m² unless rapidly progressive crescentic disease 3, 2
Ignoring infection prophylaxis: The TESTING trial fatalities highlight the need for pneumocystis prophylaxis during high-dose steroid therapy 3
Overlooking cardiovascular risk: Sub-nephrotic proteinuria is a cardiovascular risk factor; blood pressure targets must account for cardiovascular complications 3
Expecting sustained benefit after discontinuation: Proteinuria frequently recurs after stopping steroids, and the long-term legacy effect remains unproven 3
The 2025 research by the Clinical Journal of the American Society of Nephrology confirms that while glucocorticoids reduce total IgA and galactose-deficient IgA1 levels during treatment, these effects diminish after discontinuation, and the reduction in Gd-IgA1 at 6 months does not predict long-term kidney outcomes 5.