What is the initial treatment for lupus nephritis?

Initial Treatment for Lupus Nephritis

For patients with active Class III or IV lupus nephritis, initial treatment should consist of glucocorticoids plus mycophenolic acid analogs (MPAA) or low-dose intravenous cyclophosphamide, as these regimens have the best efficacy/toxicity ratio for preserving renal function and improving survival. 1

Diagnostic Approach

Before initiating treatment, a renal biopsy is essential as clinical and laboratory tests cannot accurately predict histological findings. Treatment should be guided by the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system. 1

Induction Therapy Options

The initial treatment phase (induction therapy) should follow one of these evidence-based regimens:

1. First-line options:

   • Mycophenolic acid analogs (MMF target dose: 3 g/day for 6 months) plus glucocorticoids 1
   • Low-dose intravenous cyclophosphamide (total dose 3 g over 3 months) plus glucocorticoids 1

2. Alternative options:

   • Belimumab plus either MPAA or low-dose IV cyclophosphamide plus glucocorticoids 1
   • MPAA plus calcineurin inhibitor (when eGFR >45 ml/min/1.73 m²) plus glucocorticoids 1

Glucocorticoid Regimen

The recommended glucocorticoid protocol is:

• Begin with IV methylprednisolone pulses (500-750 mg for 3 consecutive days)
• Follow with oral prednisone 0.5 mg/kg/day for 4 weeks
• Taper to ≤10 mg/day by 4-6 months 1
• Consider reduced-dose regimens when kidney and extrarenal manifestations show improvement 1

Treatment Selection Considerations

When choosing between MPAA and cyclophosphamide:

• MPAA is preferred for patients at high risk of infertility 1
• IV cyclophosphamide may benefit patients with adherence concerns 1
• Patients with adverse prognostic factors (acute deterioration in renal function, substantial cellular crescents, fibrinoid necrosis) may benefit from higher-dose cyclophosphamide regimens 1

Adjunctive Therapies

All patients with lupus nephritis should receive:

• Hydroxychloroquine to reduce flares and improve outcomes 1
• ACE inhibitors or ARBs for patients with proteinuria or hypertension 1
• Calcium and vitamin D supplementation 1
• Appropriate non-live vaccinations 1
• Statins for persistent dyslipidemia 1

Treatment Goals and Monitoring

• Aim for complete renal response (proteinuria <50 mg/mol and normal/near-normal renal function) 1
• Target partial response by 6 months and complete response by 12 months 1
• Regularly assess serum creatinine, eGFR, proteinuria, urinary sediment, complement levels (C3, C4), anti-dsDNA antibody levels, complete blood count, and blood pressure 1

Common Pitfalls and Caveats

1. Inadequate immunosuppression: Undertreatment can lead to progressive renal damage and increased mortality. Ensure appropriate dosing of both glucocorticoids and immunosuppressants.

2. Excessive glucocorticoid exposure: While essential for treatment, prolonged high-dose steroids can cause significant morbidity. Follow tapering guidelines carefully.

3. Overlooking adjunctive therapies: Hydroxychloroquine significantly improves outcomes and should not be omitted unless contraindicated.

4. Delayed treatment initiation: Early aggressive therapy is critical for preserving renal function and improving survival rates, which have improved from over 50% mortality in the 1950s-60s to less than 10% in recent years. 2

5. Inadequate monitoring: Regular assessment of disease activity markers and medication side effects is essential for optimizing outcomes.