How to manage persistent disease activity in lupus nephritis patients on chronic dialysis?

Managing Persistent Disease Activity in Lupus Nephritis Despite Chronic Dialysis

Persistent disease activity in lupus nephritis despite chronic dialysis should be managed with continued immunosuppression, particularly belimumab added to standard therapy, which has shown efficacy in improving renal parameters and decreasing disease activity in dialysis-dependent patients. 1

Causes of Persistent Disease Activity in Dialysis-Dependent Lupus Nephritis

Persistent lupus nephritis activity despite dialysis can be attributed to several factors:

1. Ongoing autoimmune activity: SLE is a systemic disease that can continue to cause inflammation even when a patient reaches end-stage renal disease (ESRD)
2. Inadequate immunosuppression: Suboptimal dosing or poor adherence to immunosuppressive medications
3. Thrombotic microangiopathy: Concurrent TMA can contribute to persistent disease activity 2
4. Antiphospholipid antibodies: These can cause dialysis-related morbidity and vascular access thrombosis 3
5. Persistent histologic activity: Kidney biopsies often reveal ongoing inflammatory activity despite clinical remission 4

Assessment of Disease Activity

Before intensifying treatment, verify that persistent disease activity exists:

• Measure SLE serologic markers (anti-dsDNA antibodies, complement levels)
• Monitor extrarenal manifestations of lupus
• Consider a kidney biopsy to confirm active inflammation versus chronic damage 2
• Rule out other causes of symptoms (infections, medication side effects)

Management Algorithm

Step 1: Optimize Current Therapy

• Verify medication adherence
• Ensure adequate dosing of current immunosuppressives by measuring drug levels when applicable 2
• Optimize glucocorticoid dosing (aim for lowest effective dose) 5
• Continue hydroxychloroquine unless contraindicated 5

Step 2: Intensify Immunosuppression if Confirmed Active Disease

• Add belimumab to standard therapy:

  • 10 mg/kg IV on days 0,14,28, then every 28 days 6, 1
  • Has shown efficacy in dialysis-dependent patients with improvement in disease activity and potential for dialysis independence 1

• Consider rituximab for refractory disease:

  • If inadequate response to standard therapy plus belimumab 2
  • Particularly effective for certain manifestations (e.g., hematologic)

• Extended course of IV cyclophosphamide:

  • For severe refractory disease not responding to other therapies 2
  • Monitor carefully for cumulative toxicity

Step 3: Address Specific Complications

• For thrombotic microangiopathy:

  • Test for ADAMTS13 activity and antiphospholipid antibodies
  • Manage according to underlying etiology (plasma exchange, eculizumab, or anticoagulation) 2

• For antiphospholipid syndrome:

  • Add anticoagulation or antiplatelet therapy 5
  • Monitor vascular access closely for thrombosis 3

Step 4: Implement Supportive Care

• Blood pressure control: Target <130/80 mmHg 7
• Lipid management: Use statins to target LDL <100 mg/dl 5
• Maintain dialysis adequacy: Optimize dialysis prescription
• Prevent infections: Appropriate vaccination and prophylaxis in heavily immunosuppressed patients 5

Monitoring Response

• Regular assessment of SLE activity markers (every 1-3 months)
• Monitor for adverse effects of immunosuppression
• Evaluate for potential recovery of renal function, especially in patients recently started on dialysis 1

Special Considerations

• Transplantation planning: Consider transplantation when lupus activity has been absent or at low level for at least 3-6 months 2
• Peritoneal dialysis: May have increased risk of infections in patients on immunosuppressive agents 2
• Vascular access: Patients with antiphospholipid antibodies have increased risk of vascular access thrombosis 3

Pitfalls to Avoid

• Don't assume all symptoms are due to ESRD: Persistent lupus activity requires continued immunosuppression
• Don't discontinue all immunosuppression when a patient reaches ESRD, as disease activity can continue
• Don't overlook non-immune factors contributing to symptoms (hypertension, volume status, anemia)
• Don't delay transplant evaluation in stable patients, as outcomes are better with preemptive transplantation 2

The evidence strongly supports that continued immunosuppression, particularly with the addition of belimumab to standard therapy, can improve outcomes in patients with persistent lupus nephritis activity despite dialysis dependence 1.