A 32-year-old woman presents with nephrotic syndrome (serum albumin 2.1 g/dL, 24-hour urine protein 8.5 g, serum creatinine 0.9 mg/dL). Kidney biopsy shows diffuse proliferative glomerulonephritis with IgA and C3 deposits. What is the drug of choice for induction therapy?

Explanation

## Induction Therapy for IgA Nephropathy with Nephrotic Presentation ### Clinical Context This patient has IgA nephropathy (IgAN) with nephrotic syndrome and preserved renal function (eGFR ~90 mL/min). The presence of diffuse proliferative changes and nephrotic-range proteinuria indicates moderate-to-severe disease requiring aggressive immunosuppression. ### First-Line Induction Regimen **Key Point:** Corticosteroids are the cornerstone of induction therapy for IgAN with nephrotic syndrome and preserved renal function. The standard induction protocol consists of: 1. **IV methylprednisolone pulses** — 0.5–1 g daily for 3 consecutive days (months 1, 3, 5) 2. **Oral prednisolone** — 0.5 mg/kg/day (max 40 mg) tapered over 6 months **High-Yield:** This combined IV pulse + oral corticosteroid approach reduces proteinuria by 30–50% and slows progression to ESRD in IgAN with nephrotic features. ### Rationale for Corticosteroids in This Setting | Feature | Rationale | |---------|----------| | **Preserved renal function** | Allows safe use of standard-dose corticosteroids without dose reduction | | **Nephrotic syndrome** | Indicates severe glomerular inflammation; requires potent anti-inflammatory agent | | **IgA deposits** | Immune-mediated disease; steroids suppress T-cell and B-cell activation | | **Diffuse proliferation** | Active endocapillary proliferation responds well to early steroid therapy | ### Clinical Pearl **Monitoring:** Check baseline glucose, BP, and bone density. Add PPI for GI protection and calcium + vitamin D supplementation during prolonged steroid therapy. ### When to Add Second-Line Agents - **Cyclophosphamide** — reserved for rapidly progressive IgAN (RPGN pattern) or crescentic disease - **Mycophenolate mofetil** — used as maintenance therapy after induction, or in steroid-sparing protocols - **Azathioprine** — maintenance agent, not first-line induction [cite:Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for IgA Nephropathy]