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?

Question

Accepted Answer

C. Corticosteroids (methylprednisolone pulses followed by oral prednisolone). ## 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]

Answer

A. Azathioprine

Answer

B. Cyclophosphamide

Answer

D. Mycophenolate mofetil

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

First-Line Induction Regimen

Rationale for Corticosteroids in This Setting

Clinical Pearl

When to Add Second-Line Agents

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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