A 35-year-old woman presents with sudden-onset haematuria, hypertension (BP 162/104 mmHg), and mild facial oedema. Serum creatinine is 2.8 mg/dL (baseline 0.9), and urinalysis shows dysmorphic RBCs, RBC casts, and 3.5 g/day proteinuria. Complement C3 is markedly reduced (8 mg/dL; normal 30). Renal ultrasound shows normal-sized kidneys. Serologies for ANA, ANCA, and anti-GBM are negative. What is the most appropriate next step in management?

Question

A 35-year-old woman presents with sudden-onset haematuria, hypertension (BP 162/104 mmHg), and mild facial oedema. Serum creatinine is 2.8 mg/dL (baseline 0.9), and urinalysis shows dysmorphic RBCs, RBC casts, and 3.5 g/day proteinuria. Complement C3 is markedly reduced (8 mg/dL; normal >30). Renal ultrasound shows normal-sized kidneys. Serologies for ANA, ANCA, and anti-GBM are negative. What is the most appropriate next step in management?

Accepted Answer

B. Perform renal biopsy urgently to confirm diagnosis and guide immunosuppressive therapy. ## Clinical Presentation Analysis

This patient presents with **rapidly progressive glomerulonephritis (RPGN)** with features suggestive of **membranoproliferative glomerulonephritis (MPGN) or C3 glomerulonephritis**:

### Key Diagnostic Clues

1. **Acute nephritic syndrome** — haematuria, hypertension, oedema, RBC casts
2. **Rapidly declining renal function** — Cr 0.9 → 2.8 mg/dL in days to weeks
3. **C3 deposition pattern** — marked C3 reduction (8 mg/dL) is hallmark of:
   - Membranoproliferative GN (MPGN)
   - C3 glomerulonephritis (C3GN)
   - Post-infectious GN (less likely given rapid progression)
4. **Negative serologies** — rules out lupus, ANCA-associated vasculitis, anti-GBM disease
5. **Normal kidney size** — excludes chronic kidney disease; acute process

## Why Renal Biopsy is Essential

**High-Yield:** In RPGN with C3 deposition and negative serologies, **renal biopsy is mandatory** to:

1. **Confirm diagnosis** — differentiate MPGN from C3GN from other patterns
2. **Assess for crescents** — presence/absence determines prognosis and treatment intensity
3. **Guide immunosuppression** — biopsy findings determine whether to use steroids ± cyclophosphamide vs. alternative agents
4. **Establish baseline** — allows comparison if repeat biopsy needed

**Key Point:** Biopsy should be performed **urgently** (within 1–2 weeks) because:
- Rapidly progressive disease may progress to end-stage renal disease
- Early immunosuppression guided by biopsy improves outcomes
- Delay risks irreversible renal damage

## Management Algorithm

```mermaid
flowchart TD
  A[RPGN + C3 deposition + Negative serology]:::outcome --> B[Urgent renal biopsy]:::action
  B --> C{Biopsy findings?}:::decision
  C -->|Crescents present| D[High-dose steroids + cyclophosphamide]:::action
  C -->|No crescents, MPGN pattern| E[Corticosteroids ± additional agents]:::action
  C -->|C3GN pattern| F[Corticosteroids; consider C5 inhibitor if severe]:::action
  D --> G[Monitor Cr, proteinuria weekly]:::action
  E --> G
  F --> G
```

## Why NOT Other Options?

### Option 1: High-dose steroids without biopsy
- **Trap:** Starting immunosuppression before biopsy diagnosis is suboptimal
- Biopsy findings determine whether additional agents (cyclophosphamide) are needed
- Steroids alone may be insufficient for crescentic disease
- Delaying biopsy risks irreversible renal damage

### Option 2: Plasma exchange immediately
- **Trap:** Plasma exchange is NOT indicated for MPGN or C3GN
- PE is reserved for:
  - Anti-GBM disease (negative here)
  - ANCA-associated vasculitis with pulmonary haemorrhage (ANCA negative here)
  - Thrombotic microangiopathies (no clinical evidence)
- Premature PE exposes patient to unnecessary morbidity

### Option 3: ACE inhibitor monotherapy
- **Trap:** Monotherapy is inadequate for RPGN
- ACE inhibitors provide renal protection but do NOT arrest rapidly progressive disease
- Waiting 4 weeks risks progression to ESRD
- This approach is appropriate only for stable, non-progressive GN

## Clinical Pearl

The **marked C3 reduction (8 mg/dL)** is the diagnostic linchpin. Combined with:
- Rapid renal decline
- Negative serologies (ANA, ANCA, anti-GBM)
- Acute nephritic picture

This pattern strongly suggests **C3-mediated GN** (MPGN or C3GN), which requires biopsy for precise classification and to assess crescentic involvement. Treatment intensity depends on biopsy findings.

## Post-Biopsy Management

**If crescents present (>50%):**
- High-dose IV methylprednisolone 500 mg daily × 3 days, then oral prednisolone 1 mg/kg/day
- Cyclophosphamide 0.5–1 g/m² IV monthly × 6 months OR oral daily

**If no crescents (MPGN/C3GN pattern):**
- Oral prednisolone 0.5–1 mg/kg/day
- Consider additional agents (mycophenolate, C5 inhibitor) based on response

Answer

A. Initiate plasma exchange immediately and defer biopsy pending clinical response

Answer

C. Start high-dose oral corticosteroids (1 mg/kg/day) and plan renal biopsy within 1 week

Answer

D. Start ACE inhibitor monotherapy and observe renal function for 4 weeks

Explanation

Clinical Presentation Analysis

Key Diagnostic Clues

Why Renal Biopsy is Essential

Management Algorithm

Why NOT Other Options?

Option 1: High-dose steroids without biopsy

Option 2: Plasma exchange immediately

Option 3: ACE inhibitor monotherapy

Clinical Pearl

Post-Biopsy Management

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