Rituximab in Membranous Nephropathy

First-Line Treatment Indications

The Kidney International society recommends rituximab as a first-line treatment option for primary membranous nephropathy with nephrotic syndrome and risk factors for disease progression, with equivalent efficacy to cyclophosphamide-based regimens and a more favorable safety profile 1, 2
For patients with primary membranous nephropathy requiring immunosuppression, rituximab should be considered as initial therapy alongside cyclophosphamide/glucocorticoids or calcineurin inhibitors, particularly when eGFR is stable 1, 2

The American Journal of Kidney Diseases recommends a rituximab dosing of either 1 gram administered on days 1 and 15, or 375 mg/m² weekly for 4 weeks—both regimens appear clinically equivalent 3

Key monitoring parameters include proteinuria and serum albumin at 3 months to assess clinical response, anti-PLA2R antibody levels to guide treatment adjustments, and B-cell depletion 1

For patients who fail calcineurin inhibitor-based therapy with stable eGFR, rituximab is the recommended next treatment option 1, 2

Important safety considerations include prophylactic trimethoprim-sulfamethoxazole to prevent Pneumocystis jirovecii pneumonia, risk of hypogammaglobulinemia with repeated cycles, and rare but serious complications such as hepatitis B reactivation and progressive multifocal leukoencephalopathy 3
The Kidney International society notes that reduced vaccine efficacy during treatment is a consideration 1

All patients receiving rituximab must continue optimal supportive care, including RAS blockade, blood pressure control to <130/80 mmHg, and management of nephrotic complications 2
Prophylactic anticoagulation should be strongly considered when serum albumin is <20 g/L or <25 g/L due to high thromboembolism risk 2

The Kidney International society advises against interpreting persistent proteinuria alone as treatment failure, and against relying solely on B-cell depletion to assess treatment efficacy 1
The Kidney International society also advises against discontinuing rituximab prematurely, as response may take 3-6 months 1

The patient has biopsy-confirmed membranous nephropathy with worsening proteinuria despite current treatment with prednisone and tacrolimus, indicating treatment resistance 4
Laboratory findings show severe proteinuria, which places the patient at high risk for disease progression 5, 6
The patient has already failed first-line therapy with calcineurin inhibitors and steroids, making rituximab an appropriate second-line therapy 4, 7
Current eGFR appears stable, which supports the use of rituximab over cyclophosphamide according to treatment algorithms 5

The 2021 KDIGO guidelines specifically recommend rituximab as a treatment option for patients with membranous nephropathy at moderate to high risk for disease progression 4, 5
For patients who have failed calcineurin inhibitor-based therapy, rituximab is recommended as the next treatment option 7
The proposed dosing regimen of 1g every 2 weeks for 2 doses is consistent with the standard rituximab protocol recommended in the KDIGO guidelines 4

For patients with resistant disease who have failed calcineurin inhibitors and have stable eGFR, rituximab is the recommended next treatment 4, 7
The KDIGO guidelines specifically outline that when initial treatment with a calcineurin inhibitor fails, switching to rituximab is appropriate 4, 5

Proteinuria and serum albumin should be evaluated after 3 months of treatment to assess clinical response 5, 6
B-cell depletion should be monitored, though it is not sufficient alone to judge efficacy 4

Prophylactic trimethoprim-sulfamethoxazole should be considered to prevent infections in patients receiving rituximab 6
Patients should continue to receive optimal supportive care, including RAS blockade and blood pressure control 6
Prophylactic anticoagulation should be considered due to the patient's hypoalbuminemia and increased thromboembolism risk 6