Initial Treatment Approach for Lupus Nephritis According to KDIGO 2024 Guidelines
According to the KDIGO 2024 guidelines, patients with active Class III or IV lupus nephritis (LN), with or without a membranous component, should be treated initially 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
Glucocorticoid Regimen
- Initial therapy typically includes:
- 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 (maximum 80 mg/day)
- Gradual taper over a few months to maintenance dose 1
First-Line Immunosuppressive Options
Option 1: MPAA-Based Regimen
- Dosing: Mycophenolate mofetil (MMF) 1.0-1.5 g twice daily or mycophenolic acid sodium 0.72-1.08 g twice daily 1
- Best for: Patients at high risk of infertility or with prior cyclophosphamide exposure 2
Option 2: Cyclophosphamide-Based Regimen
- Dosing: IV cyclophosphamide 500 mg every 2 weeks for 6 doses or oral cyclophosphamide 1.0-1.5 mg/kg/day for 3 months 1
- Best for: Patients who may have difficulty adhering to oral regimens 2
- Avoid in: Patients concerned about fertility 2
Option 3: Calcineurin Inhibitor (CNI) + MPAA
- Dosing: Voclosporin 23.7 mg twice daily with MPAA (in patients with eGFR >45 ml/min per 1.73 m²) 1
- Best for: Patients with preserved kidney function and nephrotic-range proteinuria, or those who cannot tolerate standard-dose MPAA 1
Option 4: Belimumab + MPAA or Reduced-Dose Cyclophosphamide
- Dosing: Belimumab IV 10 mg/kg every 2 weeks for 3 doses then every 4 weeks (duration up to 2.5 years) with either MPAA or IV cyclophosphamide 1
- Best for: Patients with repeated kidney flares or at high risk for progression to kidney failure due to severe CKD 1
Assessing Treatment Response
Treatment response is evaluated based on:
Complete response:
- Proteinuria <0.5 g/g (PCR)
- Stable or improved kidney function (±10-15% of baseline)
- Usually within 6-12 months of starting therapy 1
Partial response:
- ≥50% reduction in proteinuria to <3 g/g (PCR)
- Stable or improved kidney function
- Within 6-12 months of starting therapy 1
Maintenance Therapy
After completion of initial therapy:
- Recommended: MPAA for maintenance (Level 1B evidence) 1
- Dosing: MMF 750-1000 mg twice daily or MPA 540-720 mg twice daily 1
- Alternative: Azathioprine for patients who don't tolerate MPAA, lack access to MPAA, or are considering pregnancy 1
- Duration: Total immunosuppression (initial + maintenance) should be at least 36 months 1
- Glucocorticoids: Taper to lowest possible dose; consider discontinuation after 12 months of complete clinical renal response 1
Management of Unsatisfactory Response
If response is inadequate:
- Verify medication adherence
- Ensure adequate dosing (check drug levels if available)
- Consider repeat kidney biopsy if concerned about chronicity or alternative diagnosis 1
Important Considerations
- Avoid premature therapy changes if proteinuria is improving, as complete response may take 12-24 months in nephrotic patients 2
- Poor adherence is a common cause of treatment failure; consider IV cyclophosphamide for patients with adherence concerns 2
- Cyclophosphamide is associated with increased risk of alopecia compared to MMF (moderate certainty evidence) 3
- MMF is associated with increased risk of diarrhea compared to cyclophosphamide (moderate certainty evidence) 3
- Triple immunosuppressive regimens that include belimumab or a CNI can be continued as maintenance therapy 1
The KDIGO 2024 guidelines represent a significant update from previous approaches, offering multiple evidence-based options for initial therapy and emphasizing the importance of a full 36-month treatment course to minimize relapse risk.