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


METHODS
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 CNIs and other immunosuppressant drugs could be withdrawn in all patients with no evidence of relapse.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.
Segarra
Alfons
A
Servicio de Nefrología Hospital Vall d'Hebrón, Barcelona, Spain. alsegarr@vhebron.net
Praga
Manuel
M
Ramos
Natalia
N
Polanco
Natalia
N
Cargol
Isabel
I
Gutierrez-Solis
Elena
E
Gomez
M Rosa
MR
Montoro
Bruno
B
Camps
Joaquim
J
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D001706:Biopsy; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010865:Pilot Projects; D011507:Proteinuria / Q000188:drug therapy / Q000473:pathology; D012074:Remission Induction; D000069283:Rituximab; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D000069283:Rituximab; D009173:Mycophenolic Acid