Can rituximab (rituximab) be given to a patient with hypoalbuminemia and significant proteinuria?

Rituximab in Hypoalbuminemia and Significant Proteinuria

Yes, rituximab can be administered to patients with hypoalbuminemia (albumin 1.5) and significant proteinuria (4+), but treatment decisions should be based on the underlying glomerular disease, risk factors for progression, and eGFR status. 1

Risk Assessment and Treatment Decision

Determining Risk Factors

• Serum albumin of 1.5 g/dL and 4+ proteinuria indicate high-risk nephrotic syndrome, which is a risk factor for disease progression in membranous nephropathy (MN) 1
• Low serum albumin (<30 g/L) is considered a risk factor for disease progression and may warrant immunosuppressive therapy 1
• The decision to use rituximab should consider:
  • eGFR stability (stable vs. decreasing) 1
  • Previous treatments and response 1
  • Risk of disease progression 1

Treatment Algorithm Based on Risk

1. High-risk patients (with severe hypoalbuminemia and significant proteinuria):

   • Rituximab is an appropriate treatment option if eGFR is stable 1
   • If eGFR is decreasing, cyclophosphamide with glucocorticoids may be preferred 1

2. Very high-risk patients (with life-threatening nephrotic syndrome or rapidly deteriorating kidney function):

   • Cyclophosphamide with glucocorticoids is generally recommended over rituximab 1

Efficacy Considerations with Hypoalbuminemia

Potential Limitations

• Clinical observations suggest rituximab might be less effective in patients with nephrotic range proteinuria compared to non-nephrotic patients 2
• Significant amounts of rituximab may be lost in the urine in nephrotic patients, potentially requiring repeated or higher dosages 2
• The excretion of rituximab correlates with IgG urinary loss, suggesting selectivity of proteinuria as a determining factor of rituximab excretion 2

Efficacy Evidence

• Despite potential urinary losses, rituximab has demonstrated efficacy in reducing proteinuria in patients with idiopathic MN 3
• In one study, proteinuria decreased from 9.1 to 4.6 g/24h in patients with favorable tubulointerstitial scores 4
• Rituximab has shown similar efficacy in patients who failed previous immunosuppressive treatments compared to treatment-naïve patients 5

Monitoring and Follow-up

Response Assessment

• Monitor anti-PLA2R antibody levels (if applicable) at 3-6 months after starting therapy to evaluate treatment response 1
• Evaluate proteinuria and serum albumin response after 3 months of treatment 1
• Consider additional doses of rituximab if B-cell depletion is insufficient 1

Treatment Resistance

• If resistance to rituximab occurs, check compliance and monitor efficacy markers (B-cell response, anti-rituximab antibodies, IgG levels) 1
• Persistent proteinuria alone is not sufficient to define resistance; consider improvement in serum albumin as a positive response indicator 1

Important Caveats

• Patients should receive optimal supportive care including RAS blockade, blood pressure control, and management of nephrotic syndrome complications 1
• Consider prophylactic anticoagulation in patients with severe hypoalbuminemia due to increased thromboembolism risk 1
• Prophylactic trimethoprim-sulfamethoxazole should be considered in patients receiving rituximab to prevent infections 1
• Recent clinical trials confirm rituximab as a valid alternative to cyclophosphamide-glucocorticoid regimens in high-risk MN 6

By following this approach, rituximab can be safely administered to patients with hypoalbuminemia and significant proteinuria, with appropriate monitoring and supportive care measures.