Medical Necessity of Rituximab 1g x 2 Doses for Membranous Nephropathy
Rituximab 1g x 2 doses is medically necessary and represents standard-of-care therapy for this patient with membranous nephropathy who demonstrates worsening proteinuria (UPCR 3.3 g/d) despite prior treatment, placing him at high risk for disease progression. 1
Treatment Plan Medical Necessity
Risk Stratification Supports Immunosuppressive Therapy
This patient meets clear criteria for immunosuppressive treatment with proteinuria >3.5 g/d (UPCR 3.3 g/d), which indicates nephrotic-range proteinuria and high risk for disease progression. 1
The KDIGO 2021 guidelines explicitly state that immunosuppressive therapy should be considered when at least one risk factor for disease progression is present, which this patient clearly demonstrates with worsening proteinuria from 1.8 g/d (July 2025) to 3.3 g/d (October 2025). 1
The patient has stable eGFR (serum creatinine 1.4), which specifically supports rituximab over cyclophosphamide according to KDIGO treatment algorithms. 1
Evidence of Treatment Resistance or Relapse
The patient was initially treated with rituximab in October 2023, and while he showed initial improvement (proteinuria decreased to 500 mg/day in June 2025), he now demonstrates worsening proteinuria (3.3 g/d), indicating either relapse or incomplete response. 1
For patients with initial relapse after therapy, KDIGO guidelines recommend that the initial therapy can be repeated, making retreatment with rituximab appropriate. 1
The proposed dosing of 1g x 2 doses administered 2 weeks apart is the exact regimen recommended by KDIGO for retreatment. 1, 2
Standard of Care vs. Experimental Status
Rituximab is Established Standard of Care
The KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases (published in Kidney International) explicitly recommends rituximab as a Grade 1B recommendation for patients with membranous nephropathy at moderate to high risk for disease progression. 1
The guideline states: "For patients with MN and at least one risk factor for disease progression, consider using rituximab or cyclophosphamide and alternate month glucocorticoids for 6 months, or tacrolimus-based therapy for ≥6 months." 1
Rituximab is specifically listed as the preferred option for patients with stable eGFR in the KDIGO treatment algorithm. 1
Level of Evidence Supporting Rituximab
Multiple randomized controlled trials support rituximab use in membranous nephropathy, including the MENTOR trial and RI-CYCLO trial. 3, 4
A 2022 study demonstrated that rituximab can effectively reduce proteinuria and maintain stable renal function even in membranous nephropathy patients with kidney insufficiency. 5
Meta-analysis data show that rituximab achieves complete or partial remission in approximately two-thirds of treated patients with a favorable safety profile. 6, 3
Dosing Regimen is Standard
The proposed regimen of 1g IV every 2 weeks for 2 doses is the standard protocol cited in KDIGO guidelines. 1, 2
This dosing is supported by Level B evidence from randomized controlled trials, as documented in Lexicomp. 2
Alternative dosing regimens exist (375 mg/m² weekly x 4 doses), but the 1g x 2 dose protocol is most commonly used and recommended. 1, 2
Treatment Algorithm Justification
Patient Meets High-Risk Criteria
Proteinuria >3.5 g/d with worsening trend (1.8 g/d → 3.3 g/d over 3 months) indicates active disease requiring intervention. 1
The patient has demonstrated either relapse or incomplete response to initial rituximab therapy, warranting retreatment. 1
Stable serum creatinine (1.4) with preserved eGFR supports rituximab as the optimal choice over cyclophosphamide. 1
Monitoring Plan Should Include
Anti-PLA2R antibody levels should be evaluated at 3 months after rituximab to assess immunologic response. 1, 2, 7
Proteinuria and serum albumin should be monitored at 3-month intervals to evaluate clinical response. 2, 7
B-cell depletion should be assessed, though it alone is insufficient to judge efficacy; additional doses may be considered even if B cells are depleted if proteinuria persists. 1
Important Caveats
The patient should continue optimal supportive care including RAS blockade (Lisinopril-HCT), which is being appropriately continued. 1, 2
Prophylactic anticoagulation should be strongly considered given the high proteinuria and risk of thromboembolic events in nephrotic syndrome. 1
Prophylactic trimethoprim-sulfamethoxazole should be considered to prevent Pneumocystis jirovecii pneumonia during B-cell depletion. 2, 8
If the patient fails to respond to this second course of rituximab (defined by persistent proteinuria and positive anti-PLA2R antibodies at 6 months), consultation with an expert center should be pursued for consideration of alternative therapies. 1, 7
Conclusion on Medical Necessity
This treatment is medically necessary, represents standard of care per KDIGO 2021 guidelines, and is supported by Level B evidence from randomized controlled trials. 1, 2 The patient's clinical trajectory with worsening proteinuria despite supportive care, stable kidney function, and prior partial response to rituximab makes retreatment both appropriate and guideline-concordant. This is not experimental or investigational therapy—it is established first-line immunosuppressive treatment for membranous nephropathy at high risk for progression.