Initial Treatment Approach for Lupus Nephritis According to KDIGO 2024 Guidelines
For patients with active Class III or IV lupus nephritis (with or without membranous component), the KDIGO 2024 guidelines recommend initial treatment with glucocorticoids plus any one of the following: mycophenolic acid analogs (MPAA), low-dose intravenous cyclophosphamide, belimumab with either MPAA or low-dose cyclophosphamide, or MPAA with a calcineurin inhibitor. 1, 2
Glucocorticoid Regimen
The glucocorticoid component consists of:
- Optional IV methylprednisolone 0.25-0.50 g/day for 1-3 days (depending on disease severity)
- Followed by oral prednisone at 0.35-1.0 mg/kg/day (not exceeding 80 mg/day)
- Gradual taper over a few months to maintenance dose 1, 2
Four Treatment Options (to be used with glucocorticoids)
1. Mycophenolic Acid Analogs (MPAA)
- MMF 1.0-1.5 g twice daily or mycophenolic acid sodium 0.72-1.08 g twice daily
- Level 1B evidence 1
- May lead to increased complete disease remission compared to IV cyclophosphamide 3
- Associated with decreased alopecia but increased diarrhea compared to cyclophosphamide 3
2. Low-Dose Intravenous Cyclophosphamide
- IV 500 mg every 2 weeks for 6 doses or
- Oral cyclophosphamide 1.0-1.5 mg/kg/day for 3 months
- Level 1B evidence 1
- Consider in patients with adherence concerns 2
- Avoid in patients concerned about fertility 2
3. Belimumab with MPAA or Low-Dose Cyclophosphamide
- Belimumab IV 10 mg/kg every 2 weeks for 3 doses then every 4 weeks
- Duration up to 2.5 years
- Level 1B evidence 1
- Preferred for patients with repeated kidney flares or high risk for progression to kidney failure 2
4. MPAA with Calcineurin Inhibitor
- Voclosporin 23.7 mg twice daily with MPAA (in patients with eGFR >45 ml/min per 1.73 m²)
- Consider cyclosporine when voclosporin and tacrolimus are not available
- CNI duration up to 3 years 1
- Preferred in patients with preserved kidney function and nephrotic-range proteinuria 2
Treatment Selection Considerations
When choosing among the four options, consider:
Patient characteristics:
- CNI-based regimens are preferred for patients with preserved kidney function and nephrotic-range proteinuria 2
- Triple immunosuppressive regimen (belimumab + glucocorticoids + either MPAA or cyclophosphamide) is preferred for patients with repeated kidney flares or high risk for progression 2
- IV cyclophosphamide should be considered for patients with adherence concerns 2
Contraindications:
Side effect profile:
Monitoring and Response Assessment
- Monitor every 2-4 weeks initially, then adjust based on response 2
- Complete response: proteinuria <0.5 g/g, stable or improved kidney function 2
- Partial response: ≥50% reduction in proteinuria to <3 g/g, stable or improved kidney function 2
- Target UPCR below 500-700 mg/g by 12 months 2
- Response typically occurs within 6-12 months, but may take 12-24 months in nephrotic patients 2
Common Pitfalls and Caveats
- Poor adherence is a common cause of treatment failure 2
- Avoid premature therapy changes if proteinuria is improving, as complete response may take 12-24 months in nephrotic patients 2
- Predictors of poor outcomes include acute kidney injury at onset, high serum creatinine at six months, no response at six months, and presence of flare 4
- Minimize excessive glucocorticoid exposure by tapering to lowest effective dose 2
- Maintain immunosuppression for at least 36 months total to minimize risk of relapse 2
The KDIGO 2024 guidelines represent a significant update from previous approaches, offering multiple evidence-based options for initial treatment of lupus nephritis, which have dramatically improved survival rates from over 50% mortality in the 1950s and 1960s to less than 10% in recent years 3.