Successful treatment of membranous glomerulonephritis with rituximab in calcineurin inhibitor-dependent patients

Abstract

Background and objectives: Calcineurin inhibitors (CNIs) induce remission of proteinuria in most nephrotic patients with membranous glomerulonephropathy (MGN). However, 60% of patients become treatment dependent and are at risk of chronic nephrotoxicity. The aim of this study was to evaluate the efficacy of rituximab in patients with long-term dependence on CNIs.

Design, setting, participants, and measurements: Thirteen patients with MGN, normal renal function, and proven dependence on CNIs, despite previous treatment with other immunosuppressant drugs, received a single trial of four weekly doses of rituximab (375 mg/m(2)). Outcome measures were the percentage of patients with CNI withdrawal and no evidence of relapse and the percentage of patients with complete or partial remission 30 mo after CNI withdrawal.

Results: After rituximab, proteinuria decreased significantly (2.5 +/- 0,76 basal versus 0.85 +/- 0.17 at 6 mo; P = .0003). CNIs and other immunosuppressant drugs could be withdrawn in all patients with no evidence of relapse. After CNI withdrawal, GFR increased significantly (90.3 +/- 15 basal to 106.4 +/- 20 at 3 mo with a mean increase of 15.3% [range 0-20]). Three patients suffered a relapse of nephrotic proteinuria 19, 23, and 28 mo after rituximab treatment; all were successfully treated with a second course of rituximab. At 30 mo, all patients were in remission.

Conclusions: In patients with MGN with long-term CNI dependence, rituximab can be an effective tool to overcome dependence on CNI, thus avoiding the risk of nephrotoxicity related to the chronic exposure to these drugs.

Figures

Figure 1.

Evolution of CD-19+ cell count over the total observation period. Basal: CD-19+ cell counts before rituximab administration. Values within 15 and 30 mo exclude CD-19 counts of the three patients who suffered a relapse and needed retreatment.

Figure 2.

Time course of urinary protein excretion (g/24 h) in individual patients from entry into the study (basal) to end of follow-up (month 30) Values represent proteinuria in g/d