A 28-year-old man from Mumbai with biopsy-proven membranoproliferative glomerulonephritis (MPGN) type I presents with nephrotic syndrome (proteinuria 6 g/day, serum albumin 2.4 g/dL) and mild renal impairment (serum creatinine 1.8 mg/dL, eGFR 45 mL/min/1.73m²). Serum C3 is low (0.65 g/L). He is not on any immunosuppressive therapy. What is the most appropriate next step in management?

Explanation

## Clinical Context This patient has **MPGN type I with low complement (C3)**, indicating an immune-complex mediated glomerulonephritis. Key features: - Biopsy-proven MPGN (not clinical diagnosis) - Nephrotic-range proteinuria - Mild-to-moderate renal impairment (eGFR 45) - Low C3 (immune-complex disease) - No prior immunosuppression ## Rationale for Mycophenolate Mofetil (MMF) + Corticosteroids **Key Point:** MMF combined with corticosteroids is the preferred first-line immunosuppressive regimen for MPGN type I with nephrotic syndrome and renal impairment, especially when C3 is depressed. **High-Yield:** MPGN is a proliferative glomerulonephritis requiring immunosuppression, unlike minimal change disease. MMF has superior efficacy and tolerability compared to cyclophosphamide in MPGN and is now preferred in international guidelines (KDIGO 2021). ### Treatment Algorithm for MPGN Type I with Nephrotic Syndrome ```mermaid flowchart TD A[MPGN Type I + Nephrotic Syndrome]:::outcome --> B{Renal function status?}:::decision B -->|eGFR > 60| C[Corticosteroids alone or MMF + steroids]:::action B -->|eGFR 30-60| D[MMF + Corticosteroids]:::action B -->|eGFR < 30| E[Consider IV methylprednisolone pulses + MMF]:::action D --> F[Target: Proteinuria reduction to <1 g/day]:::outcome F --> G{Response at 3-6 months?}:::decision G -->|Yes| H[Continue MMF for 2 years]:::action G -->|No| I[Escalate: Add cyclophosphamide or consider rituximab]:::urgent ``` ### Why MMF Over Cyclophosphamide? | Parameter | MMF | Cyclophosphamide | |-----------|-----|------------------| | **Efficacy in MPGN** | Proven in RCTs | Older data; less favorable | | **Renal preservation** | Superior GFR preservation | More acute renal toxicity | | **Fertility** | Reversible; safe in reproductive age | Teratogenic; causes infertility | | **Infection risk** | Lower | Higher (especially CMV) | | **Monitoring burden** | Less intensive | Requires urinalysis for cystitis | | **Current guideline status** | Preferred first-line (KDIGO 2021) | Second-line for resistance | **Clinical Pearl:** In a 28-year-old man, MMF is superior to cyclophosphamide because it preserves fertility and has a better safety profile while maintaining efficacy in MPGN. ## Dosing Regimen - **Mycophenolate mofetil:** 1–1.5 g twice daily (target 2–3 g/day) - **Corticosteroids:** Prednisolone 0.5–1 mg/kg/day, tapered over 6–12 weeks - **ACE-I/ARB:** Continue as adjunctive therapy for proteinuria reduction - **Duration:** MMF continued for 2 years after remission **Mnemonic:** **MPGN-MMF** — **M**embranoproliferative **G**lomerulonephritis treated with **M**ycophenolate **M**ofetil + **F**luticosteroids