What are the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for treating lupus nephritis, classified by disease class?

KDIGO 2024 Guidelines for Lupus Nephritis Treatment by Class

The KDIGO 2024 guidelines recommend specific treatment regimens based on the histological class of lupus nephritis, with Class III and IV requiring the most aggressive therapy consisting of glucocorticoids plus immunosuppressive agents, while other classes may require less intensive approaches. 1

Class I and II Lupus Nephritis

• Minimal mesangial (Class I) and mesangial proliferative (Class II) lupus nephritis typically do not require specific immunosuppressive therapy
• Treatment focuses on:
  • Hydroxychloroquine (recommended for all SLE patients including those with LN unless contraindicated) 1
  • Management of comorbidities and risk factors
  • Blood pressure control and proteinuria management if present
  • Monitoring for progression to more severe classes

Class III and IV Lupus Nephritis (Focal and Diffuse Proliferative)

Initial Therapy

Initial treatment must include glucocorticoids plus ONE of the following regimens: 1

1. Mycophenolic acid analogs (MPAA) (1B evidence)

   • MMF 1.0-1.5g twice daily or mycophenolic acid sodium 0.72-1.08g twice daily

2. Low-dose intravenous cyclophosphamide (1B evidence)

   • IV 500mg every 2 weeks for 6 doses or
   • Oral 1.0-1.5 mg/kg/day for 3 months

3. Belimumab plus either MPAA or low-dose IV cyclophosphamide (1B evidence)

   • Belimumab 10mg/kg IV every 2 weeks for 3 doses then every 4 weeks (up to 2.5 years)

4. MPAA plus calcineurin inhibitor (1B evidence)

   • Only when eGFR >45 ml/min/1.73m²
   • Voclosporin 23.7mg twice daily with MPAA

Glucocorticoid Regimen

• IV methylprednisolone 0.25-0.50g/day for 1-3 days based on disease severity
• Followed by oral prednisone 0.35-1.0mg/kg/day (max 80mg)
• Taper over several months to maintenance dose 1
• Consider reduced-dose regimen when appropriate (see KDIGO guidelines for specific tapering schedules)

Class V Lupus Nephritis (Membranous)

• Pure Class V with nephrotic-range proteinuria: Consider MPAA plus calcineurin inhibitor (CNI) regimen
• Class V with Class III or IV components: Treat as Class III/IV (as above)
• Patients with preserved kidney function and nephrotic-range proteinuria may particularly benefit from CNI-containing regimens 1

Class VI Lupus Nephritis (Advanced Sclerotic)

• Focus on kidney-protective strategies rather than immunosuppression
• Management of CKD complications
• Preparation for kidney replacement therapy if appropriate
• Continue hydroxychloroquine

Maintenance Therapy (All Classes)

• After completion of initial therapy, patients should be placed on MPAA for maintenance (1B evidence) 1
• Maintenance should continue for at least 36 months 2
• Azathioprine is an alternative if MPAA is not tolerated or contraindicated 1
• For patients on triple therapy (belimumab + MPAA/cyclophosphamide), continue triple regimen for maintenance

Special Considerations

Treatment Selection Factors

• Fertility concerns: Avoid cyclophosphamide in patients concerned about fertility
• Adherence issues: Consider IV cyclophosphamide for patients with adherence difficulties
• Kidney function: Avoid CNIs when eGFR ≤45 ml/min/1.73m²
• Repeated flares: Consider triple immunosuppressive regimen with belimumab

Adjunctive Therapies

• Hydroxychloroquine for all patients unless contraindicated
• Blood pressure control with RAAS blockade
• Proteinuria management
• Infection prophylaxis when appropriate
• Bone health management
• UV protection
• Fertility preservation considerations

Monitoring Response

• Complete response: Proteinuria <0.5g/g, stable/improved kidney function within 6-12 months
• Partial response: ≥50% reduction in proteinuria to <3g/g, stable/improved kidney function
• Inadequate response: Consider adherence issues, drug levels, and alternative regimens

Common Pitfalls to Avoid

• Inadequate treatment duration (should be at least 36 months)
• Excessive glucocorticoid exposure
• Inappropriate CNI use in patients with significantly impaired kidney function
• Failure to prescribe hydroxychloroquine
• Inadequate monitoring of disease activity and drug toxicity
• Neglecting management of comorbidities and risk factors

The KDIGO 2024 guidelines provide a comprehensive, evidence-based approach to managing lupus nephritis based on histological classification, with the goal of improving mortality, morbidity, and quality of life outcomes through appropriate immunosuppression while minimizing treatment-related complications.