What is the management of lupus nephritis?

Management of Lupus Nephritis

For patients with lupus nephritis, treatment should include hydroxychloroquine plus glucocorticoids combined with either mycophenolic acid analogs, low-dose intravenous cyclophosphamide, belimumab with MPAA/cyclophosphamide, or MPAA with a calcineurin inhibitor when kidney function is not severely impaired. 1, 2

General Management

• All patients with SLE, including those with lupus nephritis, should receive hydroxychloroquine or equivalent antimalarial unless contraindicated 1, 2
• Adjunctive therapies should be implemented to minimize complications:
  • Cardiovascular risk management: dyslipidemia treatment, blood pressure control, low-dose aspirin during pregnancy 1
  • Renoprotection: avoid high-sodium diet, optimize blood pressure, use RAAS blockade and SGLT2 inhibitors in stable patients, avoid nephrotoxic agents 1
  • Infection prevention: screen for TB/herpes zoster history, HBV/HCV/HIV screening, consider Pneumocystis jirovecii prophylaxis 1, 2
  • Bone health: assess bone mineral density, provide calcium/vitamin D supplementation, consider bisphosphonates when appropriate 1
  • UV protection: use broad-spectrum sunscreen, limit UV exposure 1
  • Fertility preservation: consider gonadotropin-releasing hormone agonists, sperm/oocyte cryopreservation 1
  • Contraception: individualized evaluation based on thrombosis risk, age, and preference 1
  • Cancer risk: minimize lifetime cyclophosphamide exposure to <36g 1

Initial Treatment for Class III/IV Lupus Nephritis

• First-line therapy includes glucocorticoids plus one of the following regimens 1, 2:

  1. Mycophenolic acid analogs (MPAA)
  2. Low-dose intravenous cyclophosphamide
  3. Belimumab with either MPAA or low-dose intravenous cyclophosphamide
  4. MPAA with a calcineurin inhibitor (when eGFR >45 ml/min/1.73m²)

• Glucocorticoid regimen typically includes 1, 2:

  • Initial IV methylprednisolone pulses (0.25-0.5g/day for up to 3 days)
  • Followed by oral prednisone with gradual taper
  • Recent evidence supports lower initial oral glucocorticoid doses (≤0.5 mg/kg/day) following IV pulse therapy, which provides similar efficacy with fewer serious adverse events compared to higher doses 3

Specific Treatment Considerations

• MPAA-based regimens are preferred for patients at high risk of infertility 1
• Intravenous cyclophosphamide can be used for patients with adherence concerns 1
• Belimumab added to standard therapy significantly improves primary efficacy renal response (43% vs 32%) and complete renal response (30% vs 20%) compared to standard therapy alone 4
• Multitarget therapy with tacrolimus plus mycophenolate mofetil has shown superior efficacy compared to intravenous cyclophosphamide for induction therapy (45.9% vs 25.6% complete remission at 24 weeks) 5

Monitoring and Response Assessment

• Complete response is defined as 2:

  • Proteinuria <0.5 g/g
  • Stable or improved kidney function within 6-12 months

• Partial response is defined as 2:

  • ≥50% reduction in proteinuria to <3 g/g
  • Stable or improved kidney function within 6-12 months

Maintenance Therapy

• Maintenance therapy should continue for at least 36 months after initial treatment 2
• MPAA maintenance dose is approximately 750-1000 mg twice daily (or MPA 540-720 mg twice daily) 2
• Short-term high-dose intravenous cyclophosphamide followed by MMF has shown effectiveness in preventing renal relapses, ESRD, and mortality 6

Special Considerations

• For patients who relapse or cannot tolerate standard therapies, rituximab may offer benefit with acceptable toxicity 7
• In patients with lupus nephritis and thrombotic microangiopathy, test for ADAMTS13 activity/antibodies and antiphospholipid antibodies 2
• Induction therapy with short-term (six monthly pulses) high-dose IV cyclophosphamide followed by MMF is effective in preventing renal relapses, end-stage renal disease, and mortality 6