What is the management of lupus nephritis?

Management of Lupus Nephritis

The management of lupus nephritis requires a combination of immunosuppressive therapy tailored to the histological class, with Class III/IV requiring glucocorticoids plus mycophenolic acid analogs, cyclophosphamide, belimumab, or calcineurin inhibitors, while Class II generally doesn't need specific immunosuppression. 1, 2

Diagnosis and Assessment

• Kidney biopsy should be performed when there is evidence of kidney involvement, especially with persistent proteinuria ≥0.5 g/24 hours or unexplained decrease in GFR 1
• Testing for antiphospholipid antibodies, anti-dsDNA, and anti-C1q autoantibodies along with complement levels (C3 and C4) is essential in patients with suspected lupus nephritis 1
• The International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system should be used, with assessment of activity and chronicity indices 1

Initial Treatment Based on Histological Class

Class II Lupus Nephritis

• Usually does not require specific immunosuppressive therapy 1

Class III or IV Lupus Nephritis (±V)

• Immunosuppressive agents administered in combination with glucocorticoids are recommended 1
• First-line options include:
  • Mycophenolic acid analogs (MPAA) plus glucocorticoids 2
  • Low-dose intravenous cyclophosphamide plus glucocorticoids 2
  • Belimumab with either MPAA or cyclophosphamide 2
  • MPAA with a calcineurin inhibitor (when kidney function is not severely impaired) 2

Class V Lupus Nephritis

• For nephrotic-range proteinuria or when UPCR exceeds 1000 mg/g despite optimal renin-angiotensin-aldosterone system blockers, glucocorticoids and immunosuppression are recommended 1
• Treatment options include glucocorticoids plus MPAA, cyclophosphamide, or calcineurin inhibitors 1, 2

Glucocorticoid Regimen

• Initial IV methylprednisolone pulses (0.25-0.5 g/day for up to 3 days) followed by oral prednisone is recommended 2
• Limited intravenous methylprednisolone pulses at treatment initiation may allow reduced dosing and more rapid tapering of oral glucocorticoids 1

Maintenance Therapy

• Total duration of initial immunosuppression plus maintenance immunosuppression for proliferative LN should be ≥36 months 1
• Recommended dose for MPAA maintenance is approximately 750-1000 mg twice daily for mycophenolate mofetil, or 540-720 mg twice daily for mycophenolic acid 1
• Patients treated with triple immunosuppressive regimens (including belimumab or a calcineurin inhibitor) can continue with this regimen during maintenance 1
• If MPAA and azathioprine cannot be used for maintenance, calcineurin inhibitors, mizoribine, or leflunomide can be considered 1

Assessing Treatment Response

• Complete response: Reduction in proteinuria <0.5 g/g, stabilization or improvement in kidney function within 6-12 months 1
• Partial response: Reduction in proteinuria by at least 50% and to <3 g/g, stable/improved kidney function within 6-12 months 1
• No kidney response: Failure to achieve partial or complete response within 6-12 months 1
• Treatment aims for at least 25% reduction in proteinuria by 3 months, 50% by 6 months, and a UPCR target below 500-700 mg/g by 12 months 1

Management of Unsatisfactory Response

When response to therapy is unsatisfactory, follow this algorithm:

1. Verify adherence to treatment 1
2. Ensure adequate dosing of immunosuppressive medications by measuring plasma drug levels if applicable 1
3. Consider repeat kidney biopsy if concerned about chronicity or other diagnoses (e.g., thrombotic microangiopathy) 1
4. Consider switching to an alternative recommended treatment regimen for persistent active disease 1
5. For refractory disease, consider:
   • Addition of rituximab or other biologic therapies 1
   • Extended course of intravenous pulse cyclophosphamide 1
   • Enrollment in clinical trials if eligible 1

Treatment of Relapse

• After complete or partial remission, relapse should be treated with the same initial therapy used to achieve the original response, or an alternative recommended therapy 1

Special Situations: Lupus Nephritis with Thrombotic Microangiopathy

• Test for ADAMTS13 activity/antibodies and antiphospholipid antibodies 1
• Start plasma exchange and glucocorticoids while awaiting test results 1
• Management should be guided by the underlying etiology of TMA 1

Adjunctive Therapies

• Hydroxychloroquine should be prescribed for all SLE patients, including those with lupus nephritis, unless contraindicated 2
• Manage dyslipidemia and optimize blood pressure control 2
• Use renin-angiotensin system blockade for proteinuria management 1
• Avoid high-sodium diet and nephrotoxic agents 2

Monitoring for CKD Progression

• Management must include measures to slow or stop CKD progression beyond immunosuppression 1
• Focus on blood pressure control, renin-angiotensin-aldosterone system blockade, flare prevention, and nephrotoxin avoidance 1