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?

Question

Accepted Answer

C. Start mycophenolate mofetil (MMF) 1–1.5 g twice daily with corticosteroids. ## 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

Answer

A. Start prednisolone 1 mg/kg/day and cyclophosphamide pulse therapy

Answer

B. Perform repeat renal biopsy to assess activity and chronicity indices

Answer

D. Initiate ACE inhibitor at maximum tolerated dose and monitor renal function

Explanation

Clinical Context

Rationale for Mycophenolate Mofetil (MMF) + Corticosteroids

Treatment Algorithm for MPGN Type I with Nephrotic Syndrome

Why MMF Over Cyclophosphamide?

Dosing Regimen

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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