Rituximab in the Treatment of Idiopathic Membranous Nephropathy
Status:
Completed
Trial end date:
2012-04-01
Target enrollment:
Participant gender:
Summary
Membranous glomerulopathy (MN) is still the most common glomerular disease associated with
nephrotic proteinuria (NS). Up to 40% of patients reach end stage renal failure (ESRD),
making MN the 2nd or 3rd most common cause of ESRD caused by a primary glomerulopathy.
Current treatment options include corticosteroids, alkylating agents, and cyclosporin, but
their use is controversial and the associated adverse effects and high cost temper their
usage. Experimental data in MN suggests that B cell activation results in immunoglobulin
deposition along the glomerular basement membrane causing injury to the membrane and
subsequent proteinuria. Drugs that non-selectively inhibit B cells and, these pathogenic
antibodies, are closely associated with improved outcomes. Based on the rationale that
selective depletion of B cells in humans would prevent the production of ?nephrotoxic?
immunoglobulins and subsequent renal injury we recently treated 15 patients with MN with
rituximab 1g i.v. twice (day 1 and day 15). Baseline proteinuria of 13.0±5.5g/24h decreased
to 9.1±7g, 9.7±8g and 6.5±6 g/24h at 3, 6, and 9 months, respectively (mean ± SD). Analysis
of the pharmacokinetic data obtained from this study, however, suggests that in heavily
nephrotic patients, rituximab dosed in this fashion results in patients being under-treated.
The present study propose to test the hypothesis that rituximab, given in accordance to the
standard lymphoma protocol (375mg/m2 x 4), will result in a more effective and profound
depletion of B cells, a more complete suppression of pathogenic antibodies, and a higher
remission rate of the NS while maintaining a favorable safety profile.