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To the Editor:

In a recent issue of the American Journal of Transplantation, El-Zoghby and colleagues (1) observed that membranous nephropathy (MN) recurred in 40% to 50% of renal transplant recipients, independent of concomitant immunosuppressive therapies. Eight of these patients received rituximab therapy that effectively reduced proteinuria, but was associated with serious infections, such as pneumonia and histoplasmosis. Dosing consisted of two separate 1000 mg infusions (two weeks apart) in all patients but one, who received a single infusion due to financial issues.

Rituximab is generally well tolerated, even when patients are repeatedly exposed to the drug (2). However, when added on steroid and antiproliferative agents to cure lymphomas or autoimmune diseases, rituximab has been reported to increase the risk of opportunistic infections and of relatively rare diseases such as JC virus-induced progressive multifocal leukoencephalopathy (3). Conceivably, heavy immunosuppression plays a central role in the pathogenesis of these potentially fatal complications and avoiding unnecessary overexposure to lymphocytolytic therapy might help preventing treatment-related events in this high-risk population.

In 29 patients given four weekly doses of 375 mg/m2 to treat MN, a full B-lymphocyte depletion was observed already after the first rituximab administration (4). Consistently, in a matched-cohort study, rituximab treatment titrated to circulating B lymphocytes was as effective as the four-dose protocol in inducing MN remission, but was better tolerated and required fewer hospitalizations (5). Thus, avoiding repeated drug exposure—in addition to reduce treatment costs—allowed limitation of adverse events of rituximab without affecting the efficacy of treatment. Conceivably, a similar approach might improve the tolerability of rituximab therapy in patients with posttransplant recurrent MN who may be at increased risk because of concurrent use of antirejection therapy and previous exposure to immunosuppressive medications to treat their primary glomerular disease. In this regard, it would be interesting to know whether the patient who in the El-Zoghby report (1) received a single rituximab administration had side effects comparable to those observed in those exposed to repeated treatments. Controlled studies are needed to address the optimal dosing strategy for rituximab therapy in this high-risk population.

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