A 35-year-old man with biopsy-proven minimal change disease (MCD) presents with nephrotic syndrome (proteinuria 6 g/day, serum albumin 2.3 g/dL, edema). He has no contraindications to corticosteroids. What is the drug of choice for induction of remission?

Explanation

## First-Line Therapy in Minimal Change Disease **Key Point:** Corticosteroids (prednisolone) are the gold-standard first-line treatment for minimal change disease (MCD) and induce complete remission in 90–95% of patients within 8–16 weeks. ### Why Prednisolone is First-Line in MCD **High-Yield:** MCD is exquisitely steroid-responsive; >90% of patients achieve complete remission with corticosteroids alone. Immunosuppressive agents are reserved for steroid-dependent or steroid-resistant disease. **Clinical Pearl:** MCD accounts for 85–90% of nephrotic syndrome in children and 10–15% in adults. The dramatic response to steroids is pathognomonic and should prompt consideration of MCD even without biopsy in children. ### Standard Induction Regimen **Dosing Protocol:** - **Prednisolone:** 1 mg/kg/day (max 80 mg/day) for 4 weeks, then taper over 8–12 weeks - Alternative: 0.5 mg/kg/day for 8 weeks, then taper - Typical total duration: 12–16 weeks - Monitor for remission: urinalysis for proteinuria; target = <0.3 g/day (complete remission) ### Mechanism of Action 1. **T-cell dysfunction correction:** MCD is thought to involve abnormal T-cell-derived cytokines (IL-13, vascular permeability factor) causing podocyte dysfunction 2. **Immune suppression:** Corticosteroids reduce T-cell proliferation and cytokine production 3. **Restoration of glomerular permselectivity:** Restores the charge and size selectivity of the glomerular filtration barrier ### Adjunctive Measures | Intervention | Purpose | Dose/Duration | |---|---|---| | **ACE inhibitor / ARB** | Reduce proteinuria; renal protection | Standard antihypertensive dose | | **Loop diuretic** | Manage edema | As needed for fluid overload | | **NSAIDs** | Adjunctive antiproteinuric effect | Short-term only; monitor renal function | | **PPI** | Gastroprotection during steroid therapy | Omeprazole 20 mg daily | **Warning:** NSAIDs should be avoided in nephrotic syndrome with significant hypoalbuminemia (risk of acute kidney injury and thrombotic complications). ### When to Use Alternative Agents **Cyclophosphamide, mycophenolate mofetil, and tacrolimus are NOT first-line** but are used in: - **Steroid-dependent MCD** (relapse within 2 weeks of steroid taper or during tapering): Cyclophosphamide or mycophenolate mofetil - **Steroid-resistant MCD** (no remission after 16 weeks of prednisolone): Cyclophosphamide, tacrolimus, or mycophenolate mofetil - **Frequent relapsers** (>2 relapses in 6 months): Cyclophosphamide or mycophenolate mofetil for steroid-sparing effect ### Treatment Algorithm for MCD ```mermaid flowchart TD A[Minimal Change Disease + Nephrotic Syndrome]:::outcome --> B[Start Prednisolone 1 mg/kg/day]:::action B --> C{Response at 4-8 weeks?}:::decision C -->|Complete remission| D[Taper prednisolone over 8-12 weeks]:::action C -->|No remission| E[Continue for 16 weeks total]:::action E --> F{Remission achieved?}:::decision F -->|Yes| D F -->|No| G[Steroid-resistant MCD]:::outcome G --> H[Add cyclophosphamide or tacrolimus]:::action D --> I{Relapse during/after taper?}:::decision I -->|Yes, frequent| J[Steroid-dependent MCD]:::outcome J --> K[Cyclophosphamide or MMF for steroid-sparing]:::action I -->|No| L[Maintenance: low-dose prednisolone PRN]:::action ``` **Key Point:** Prednisolone monotherapy is sufficient for initial induction in MCD; immunosuppressive agents are added only if steroid-dependence or resistance develops.