What are the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for managing lupus nephritis?

KDIGO 2024 Guidelines for the Management of Lupus Nephritis

The KDIGO 2024 guidelines recommend that patients with active lupus nephritis should be treated with hydroxychloroquine plus a combination of glucocorticoids and immunosuppressive therapy, with treatment regimens tailored to the specific class of lupus nephritis and maintained for at least 36 months. 1

General Management Recommendations

• Hydroxychloroquine: All patients with SLE, including those with lupus nephritis, should receive hydroxychloroquine unless contraindicated (1C recommendation) 1

• Adjunctive therapies should be implemented to minimize complications:

  • Cardiovascular risk management (dyslipidemia treatment, blood pressure control)
  • Proteinuria and CKD progression management (RAAS blockade, SGLT2 inhibitors in stable patients)
  • Infection risk reduction (screening for HBV, HCV, HIV; consider Pneumocystis prophylaxis)
  • Bone health (calcium and vitamin D supplementation)
  • UV protection (sunscreen, limiting exposure)
  • Fertility preservation when using cyclophosphamide 1

Class-Specific Treatment Recommendations

Class III/IV Lupus Nephritis (Proliferative)

Initial Therapy should include glucocorticoids plus one of the following (1B recommendation):

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) 1

Glucocorticoid Regimen:

• Initial IV methylprednisolone 0.25-0.5g/day for 1-3 days (based on severity)
• Followed by oral prednisone 0.35-1.0 mg/kg/day (maximum 80mg/day)
• Taper over several months to maintenance dose 1
• Consider reduced-dose regimen when kidney and extrarenal manifestations show improvement 1

Specific Immunosuppressive Regimens:

• MPAA: MMF 1.0-1.5g twice daily or mycophenolic acid sodium 0.72-1.08g twice daily
• Cyclophosphamide: IV 500mg every 2 weeks for 6 doses or oral 1.0-1.5 mg/kg/day for 3 months
• Belimumab: IV 10mg/kg every 2 weeks for 3 doses then every 4 weeks (up to 2.5 years)
• CNI + MPAA: Voclosporin 23.7mg twice daily with MPAA (for eGFR >45 ml/min/1.73m²) 1

Maintenance Therapy

• Continue maintenance immunosuppression for at least 36 months after initial therapy 1

• Options include:

  • Lower-dose MPAA (approximately 750-1000mg twice daily)
  • Lower-dose MPA (approximately 540-720mg twice daily) 1
  • Azathioprine (2 mg/kg/day) if intolerant to MPAA 2

• Patients treated with triple immunosuppressive regimens (including belimumab or CNI) can continue with the triple regimen for maintenance 1

Monitoring and Response Assessment

Definition of Treatment 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 within 6-12 months
• No response: Failure to achieve partial or complete response within 6-12 months 1

For Unsatisfactory Response:

1. Verify treatment adherence
2. Check drug levels if applicable (mycophenolic acid levels, cyclophosphamide infusion records)
3. Consider repeat biopsy if concerned about chronicity or other diagnoses
4. Switch to alternative recommended regimen if persistent active disease
5. For refractory cases, consider:
   • Adding rituximab or other biologics
   • Extended course of IV pulse cyclophosphamide
   • Clinical trial enrollment 1

Special Situations

Lupus Nephritis with Thrombotic Microangiopathy (TMA)

• Test for ADAMTS13 activity and antibodies, and antiphospholipid antibodies
• Management depends on underlying etiology:
  • Low ADAMTS13 activity: Plasma exchange + glucocorticoids + rituximab ± caplacizumab
  • Antiphospholipid antibody-associated: Anticoagulation ± plasma exchange
  • Complement-mediated: Consider eculizumab 1

Relapse Management

• Treat with the same initial therapy that achieved the original response, or an alternative recommended therapy 1

Common Pitfalls and Caveats

1. Inadequate treatment duration: Maintain immunosuppression for at least 36 months to prevent relapse 1

2. Excessive glucocorticoid exposure: Consider reduced-dose regimens when appropriate to minimize steroid-related complications 1

3. Inappropriate CNI use: Avoid calcineurin inhibitors in patients with significantly impaired kidney function (eGFR ≤45 ml/min/1.73m²) due to increased risk of nephrotoxicity 1

4. Inadequate monitoring: Regular assessment of proteinuria, serum creatinine, eGFR, complement levels, and anti-DNA antibodies is essential 2

5. Failure to address comorbidities: Cardiovascular disease, infections, and bone complications must be actively managed alongside lupus nephritis 1

6. Overlooking hydroxychloroquine: This is a cornerstone therapy that reduces renal flares and cumulative damage 1, 2