Treatment of Type 2 RPGN Associated with IgA Nephropathy
Initiate immediate immunosuppression with high-dose corticosteroids (pulse IV methylprednisolone 500-1000 mg daily for 3 days, then oral prednisone 0.8 mg/kg/day) combined with cyclophosphamide (1.5 mg/kg/day orally) for IgA nephropathy presenting with rapidly progressive glomerulonephritis and crescentic changes. 1, 2
Immediate Treatment Initiation
Do not delay treatment waiting for biopsy confirmation if clinical presentation strongly suggests RPGN (rapid creatinine rise over days to weeks, active urinary sediment with glomerular hematuria, proteinuria). 3, 1 The only absolute requirement before starting immunosuppression is excluding active infection with maximum certainty possible. 3, 1
Specific Treatment Protocol for Crescentic IgA Nephropathy
Induction Phase
Start pulse IV methylprednisolone 500-1000 mg daily for 3 consecutive days, followed by oral prednisolone 0.8 mg/kg/day initially, reducing to 0.4 mg/kg after 4 weeks. 1, 2
Add oral cyclophosphamide 1.5 mg/kg/day and continue until clinical response plateaus (typically 12-25 weeks, mean 17.8 weeks). 2
Rituximab can be considered as an alternative to cyclophosphamide in patients with concerns about cyclophosphamide toxicity, though cyclophosphamide remains preferred for severe kidney dysfunction (serum creatinine >4 mg/dl). 3, 1
Maintenance Phase
After cyclophosphamide discontinuation, transition to oral prednisolone 5-7.5 mg daily plus azathioprine 1 mg/kg/day for 2 years. 2
Continue tapering corticosteroids gradually over at least 6 months from initial high-dose therapy. 3, 1
Evidence Supporting Aggressive Treatment
The strongest evidence comes from a 2001 study showing that crescentic IgA nephropathy (25-70% glomeruli with active cellular crescents) treated with this regimen achieved significant improvements: serum creatinine fell from mean 149.6 to 116.4 μmol/L (p=0.01), creatinine clearance improved from 57.1 to 87.2 ml/min (p=0.004), and proteinuria decreased from 4.54 to 1.2 g/24h (p=0.004). 2 Repeat biopsies demonstrated healing of crescents and reduction in acute inflammatory changes in all but one patient. 2
Critical Contraindications to Treatment
Withhold immunosuppression only if kidney biopsy shows extensive chronic changes (high degree of interstitial fibrosis and tubular atrophy, extensive glomerulosclerosis) without active necrotizing or crescentic lesions, particularly when eGFR <30 mL/min/1.73 m². 1 The decision must be based on biopsy findings showing renal viability, not eGFR alone. 1
Do treat patients with preserved renal parenchyma and acute tubular necrosis superimposed on active crescentic disease, regardless of current eGFR. 1
Role of Plasma Exchange
Plasma exchange is NOT routinely recommended for immune complex-mediated RPGN including crescentic IgA nephropathy. 1 Historical case reports showed only transient benefit with long-term deterioration despite initial stabilization. 4 Reserve plasma exchange only for exceptional situations such as severe pulmonary hemorrhage or overlap with anti-GBM disease. 1
Special Consideration: ANCA-Positive IgA Nephropathy
If anti-myeloperoxidase (MPO) antibodies are detected alongside IgA deposits, this represents an overlap syndrome between microscopic polyangiitis and IgA nephropathy. 5 These patients particularly benefit from early aggressive immunosuppression with methylprednisolone and cyclophosphamide, with case series showing recovery from dialysis-dependence when treated promptly. 5
Common Pitfalls to Avoid
Delaying treatment while awaiting biopsy results—compatible clinical presentation (rapid GFR decline, active sediment, proteinuria) is sufficient to begin therapy. 3, 1
Assuming all patients with low eGFR should not be treated—active crescentic disease warrants treatment regardless of eGFR if biopsy shows viable parenchyma. 1
Discontinuing cyclophosphamide too early—continue until clinical response plateaus, typically 12-25 weeks. 2
Starting immunosuppression without adequately excluding infection—this is the only absolute contraindication to immediate treatment. 3, 1
Monitoring Response
Obtain repeat kidney biopsy after treatment plateau to document histological improvement and guide maintenance therapy decisions. 2 Expect improvement in serum creatinine, creatinine clearance, and proteinuria within 2-4 months if treatment is effective. 2, 6