A 35-year-old woman with a 10-year history of systemic lupus erythematosus (SLE) presents with hematuria, proteinuria (2.5 g/day), and serum creatinine of 1.8 mg/dL. Antinuclear antibody (ANA) is positive, anti-dsDNA titre is elevated, and C3/C4 levels are low. Kidney biopsy shows proliferative lupus nephritis (Class IV) with crescent formation in 15% of glomeruli. What is the drug of choice for induction immunosuppression in this patient?

Question

Accepted Answer

C. Corticosteroids + cyclophosphamide or mycophenolate mofetil. ## Diagnosis: Lupus Nephritis Class IV with Crescent Formation

The clinical and pathological findings are diagnostic:
- SLE with positive ANA and anti-dsDNA antibodies
- Active nephritis with hematuria, proteinuria (2.5 g/day), and elevated creatinine
- Hypocomplementemia (low C3/C4) — marker of active lupus
- Class IV proliferative lupus nephritis with crescent formation (15%) — high-risk disease

## Induction Therapy for Proliferative Lupus Nephritis

**High-Yield:** The standard induction regimen for Class III/IV lupus nephritis is:

$$	ext{Corticosteroids + (Cyclophosphamide OR Mycophenolate Mofetil)}$$

**Key Point:** Both cyclophosphamide and mycophenolate mofetil (MMF) are equally effective for induction, with comparable remission rates (~60–70% at 6 months). Choice depends on:
- **Cyclophosphamide:** Preferred in severe disease, RPGN, or crescent formation (as in this case)
- **MMF:** Preferred in young women of childbearing age due to lower teratogenicity and gonadal toxicity

**Clinical Pearl:** Corticosteroids are ALWAYS part of induction therapy in lupus nephritis. High-dose IV methylprednisolone (500–1000 mg daily × 3 days) followed by oral prednisone (0.5–1 mg/kg/day) is standard. Cyclophosphamide is typically given as IV pulses (0.5–1 g/m² monthly × 6 months) or daily oral dosing.

**Mnemonic: LUPUS NEPHRITIS INDUCTION = "COMBO"**
- **C**orticosteroids (always)
- **O**ne of: Cyclophosphamide or MMF
- **M**ycophenolate (alternative to CYC)
- **B**oth are evidence-based
- **O**ther agents (azathioprine, rituximab) are for maintenance/resistant disease

## Comparison of Induction Regimens

| Regimen | Remission Rate | Adverse Effects | Best For |
|---------|----------------|-----------------|----------|
| **Corticosteroids + CYC** | 60–70% | Gonadal toxicity, infection, hemorrhagic cystitis | Severe disease, RPGN, crescents |
| **Corticosteroids + MMF** | 60–70% | GI upset, teratogenicity | Young women, mild-moderate disease |
| **Corticosteroids alone** | 30–40% | Inadequate for proliferative disease | Class I/II only |
| **Azathioprine** | Not first-line | Hepatotoxicity | Maintenance therapy only |

**Warning:** Azathioprine is NOT used for induction; it is reserved for maintenance therapy after remission is achieved with cyclophosphamide or MMF.

[cite:Harrison 21e Ch 279; Robbins 10e Ch 20]

Answer

A. Rituximab monotherapy

Answer

B. ACE inhibitors alone

Answer

D. Azathioprine monotherapy

Explanation

Diagnosis: Lupus Nephritis Class IV with Crescent Formation

Induction Therapy for Proliferative Lupus Nephritis

Comparison of Induction Regimens

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Regimen	Remission Rate	Adverse Effects	Best For
Corticosteroids + CYC	60–70%	Gonadal toxicity, infection, hemorrhagic cystitis	Severe disease, RPGN, crescents
Corticosteroids + MMF	60–70%	GI upset, teratogenicity	Young women, mild-moderate disease
Corticosteroids alone	30–40%	Inadequate for proliferative disease	Class I/II only
Azathioprine	Not first-line	Hepatotoxicity	Maintenance therapy only