What is the best course of treatment for a 44-year-old woman with a history of lupus nephritis (Systemic Lupus Erythematosus with kidney involvement), previous non-response to Rituximab (rituximab), and current presentation of abdominal pain, while on Wysolone (prednisolone) 10 mg?

Treatment of Refractory Lupus Nephritis with Significant Proteinuria

For a 44-year-old woman with lupus nephritis (Class V) who failed to respond to Rituximab and presents with significant proteinuria (uPCR 5.6), switching to a calcineurin inhibitor-based regimen combined with mycophenolic acid analogs is recommended as the most effective next treatment option.

Case Summary

• 44-year-old female with:
  • Class V lupus nephritis diagnosed in 2000
  • History of stroke at age 19
  • Previous treatment with Eurolupus regimen with remission after 4 years
  • Failed response to Rituximab (2 doses 2 years ago)
  • Current medications: Wysolone (prednisolone) 10 mg daily
  • Current presentation: Abdominal pain with significant proteinuria (uPCR 5.6)
  • Preserved renal function (creatinine 0.6)
  • No active urinary sediments
  • Normal C3 (108), slightly low C4 (17)
  • Vision in only one eye due to traumatic injury

Treatment Algorithm for Refractory Lupus Nephritis

Step 1: Verify Treatment Failure

• Confirm non-adherence is not the issue 1
• Review previous Rituximab administration records
• Confirm adequate dosing was achieved

Step 2: Consider Repeat Kidney Biopsy

• Recommended to assess:
  • Current disease activity
  • Chronicity index
  • Potential transformation to another class
  • Rule out thrombotic microangiopathy 1

Step 3: Treatment Selection for Refractory Disease

First-line options for refractory disease:

1. Switch to calcineurin inhibitor (CNI) + MPAA combination 1

   • Particularly appropriate for this patient with:
     • Preserved kidney function (creatinine 0.6)
     • Class V disease with significant proteinuria (uPCR 5.6)
     • Previous failure of Rituximab

2. Alternative options:

   • Extended course of IV cyclophosphamide 1
   • Triple therapy with belimumab + MPAA/cyclophosphamide + glucocorticoids 1

Step 4: Glucocorticoid Management

• Current dose: Wysolone (prednisolone) 10 mg daily
• Consider short course of IV methylprednisolone pulses (0.25-0.5g/day for up to 3 days) 1
• Maintain or taper oral steroids based on response

Step 5: Adjunctive Therapies

• Ensure hydroxychloroquine is included (unless contraindicated)
• Add RAAS blockade for proteinuria
• Consider SGLT2 inhibitors for renoprotection
• Optimize blood pressure control 1

Rationale for Recommended Approach

The patient has several important characteristics that guide treatment selection:

1. Class V lupus nephritis with significant proteinuria: Class V disease with nephrotic-range proteinuria (uPCR 5.6) often responds well to calcineurin inhibitors, which have specific effects on podocyte function 1.

2. Failed response to Rituximab: Despite evidence supporting rituximab in refractory lupus nephritis 1, 2, this patient has already demonstrated non-response to this therapy. The KDIGO guidelines specifically recommend considering alternative therapies when there is persistent active disease despite previous treatment 1.

3. Preserved kidney function: With normal creatinine (0.6), the patient is an ideal candidate for calcineurin inhibitors, which are particularly effective in patients with preserved kidney function (eGFR >45 ml/min) 1.

Important Considerations

• Monitoring: Close monitoring of kidney function, proteinuria, and drug levels (for CNIs) is essential
• Infection risk: Vigilance for infections with combined immunosuppression
• Antiphospholipid antibodies: Given history of stroke at young age, results of APLA screen are important for management
• Vision impairment: Consider medication side effect profiles given patient has vision in only one eye

Pitfalls to Avoid

1. Continuing ineffective therapy: Continuing with Rituximab despite previous failure would not be recommended 1

2. Inadequate immunosuppression: Maintaining only low-dose steroids (current Wysolone 10mg) without additional immunosuppression is insufficient for active lupus nephritis with significant proteinuria 1

3. Overlooking medication adherence: Always verify adherence before changing therapy 1

4. Ignoring extrarenal manifestations: Current abdominal pain warrants evaluation for other lupus manifestations or complications

The evidence strongly supports that in patients with Class V lupus nephritis with significant proteinuria and preserved kidney function who have failed Rituximab therapy, a calcineurin inhibitor-based regimen combined with mycophenolic acid analogs offers the best chance for achieving remission and preserving long-term kidney function 1.