What is the management and follow-up plan for lupus nephritis?

Management and Follow-up of Lupus Nephritis

Patients with lupus nephritis should be treated with glucocorticoids plus one of the following: mycophenolic acid analogs, low-dose intravenous cyclophosphamide, belimumab with either MPAA or cyclophosphamide, or MPAA with a calcineurin inhibitor when kidney function is not severely impaired. 1

Initial Treatment of Active Lupus Nephritis

First-Line Therapy for Class III/IV Lupus Nephritis

• Glucocorticoids plus one of the following regimens 1:
  • Mycophenolic acid analogs (MPAA) 1
  • Low-dose intravenous cyclophosphamide 1
  • Belimumab with either MPAA or low-dose intravenous cyclophosphamide 1, 2
  • MPAA with a calcineurin inhibitor (CNI) when eGFR >45 ml/min per 1.73 m² 1

Glucocorticoid Regimens

• Initial IV methylprednisolone pulses (0.25-0.5 g/day for up to 3 days) followed by oral prednisone 1
• Consider reduced-dose glucocorticoid regimen when kidney and extrarenal manifestations show improvement 1
• Taper oral prednisone gradually over several months to maintenance dose 1

Special Considerations for Initial Therapy

• MPAA-based regimen is preferred for patients at high risk of infertility or with prior cyclophosphamide exposure 1
• IV cyclophosphamide may be used for patients with adherence difficulties to oral regimens 1
• Hydroxychloroquine should be prescribed for all SLE patients, including those with lupus nephritis, unless contraindicated 1

Maintenance Therapy

• Maintenance therapy should continue for at least 36 months after initial treatment 1
• For MPAA maintenance, recommended dose is approximately 750-1000 mg twice daily (or MPA 540-720 mg twice daily) 1
• Patients treated with triple immunosuppressive regimens (including belimumab or CNI) can continue with the triple regimen for maintenance 1
• Lower steroid doses should be targeted during maintenance phase 1, 3

Monitoring and Assessing Treatment Response

Definition of Treatment Response

• Complete response: Proteinuria <0.5 g/g, stable/improved kidney function within 6-12 months 1
• Partial response: ≥50% reduction in proteinuria to <3 g/g, stable/improved kidney function within 6-12 months 1
• No response: Failure to achieve partial or complete response within 6-12 months 1

Management of Unsatisfactory Response

• Verify treatment adherence 1
• Ensure adequate dosing of immunosuppressive medications (check drug levels if applicable) 1
• Consider kidney rebiopsy if concerned about chronicity or other diagnoses 1
• Consider switching to alternative recommended treatment regimen 1
• For refractory cases, consider rituximab, extended course of IV cyclophosphamide, or clinical trials 1, 3

Management of Relapse

• Treat relapse with the same initial therapy that achieved the original response or an alternative recommended therapy 1
• Consider kidney biopsy if diagnosis of flare remains uncertain 1

Adjunctive Therapies and Risk Mitigation

Cardiovascular Risk Management

• Manage dyslipidemia 1, 4
• Consider low-dose aspirin during pregnancy 1
• Optimize blood pressure control 1, 4

Kidney Protection

• Avoid high-sodium diet 1, 4
• Use renoprotective medications (RAAS blockade, SGLT2 inhibitors) in stable patients 1, 4
• Avoid nephrotoxic agents 1, 4
• Prevent acute kidney injury 1

Infection Risk Management

• Screen for herpes zoster and tuberculosis history 1
• Screen for HBV, HCV, HIV, and provide HBV vaccination 1
• Consider Pneumocystis jirovecii prophylaxis 1
• Individualize recombinant zoster vaccine consideration 1

Bone Health

• Assess bone mineral density and fracture risk 1
• Provide calcium and vitamin D supplementation 1
• Consider bisphosphonates when appropriate 1

Other Important Considerations

• Minimize UV light exposure and use broad-spectrum sunscreen 1
• Address fertility concerns with gonadotropin-releasing hormone agonists or cryopreservation 1
• Provide contraception counseling 1
• Minimize lifetime cyclophosphamide exposure to <36 g to reduce cancer risk 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
• Manage according to underlying etiology:
  • SLE-associated thrombotic thrombocytopenic purpura: Plasma exchange + glucocorticoids + rituximab ± caplacizumab 1
  • Complement-mediated TMA: Consider eculizumab 1
  • Antiphospholipid syndrome nephropathy: Anticoagulation ± plasma exchange 1

Pitfalls and Caveats

• Failure to use hydroxychloroquine in all SLE patients (unless contraindicated) increases risk of flares 1
• Prolonged high-dose glucocorticoid therapy leads to significant adverse effects; consider reduced-dose regimens when possible 1, 5
• Inadequate duration of maintenance therapy increases relapse risk 1, 5
• Overlooking non-immune risk factors for CKD progression can accelerate kidney damage 4
• Neglecting to monitor for drug-specific toxicities (e.g., cyclophosphamide-related infertility, CNI nephrotoxicity) 1, 5