Low-Dose Rituximab for Posttransplant Recurrent Membranous Nephropathy

To the Editor: In a recent issue of the American Journal of Transplantation, El-Zoghby and colleagues (1El-Zoghby ZM Grande JP Fraile MG et al.Recurrent idiopathic membranous nephropathy: Early diagnosis by protocol biopsies and treatment with anti-CD20 monoclonal antibodies.Am J Transplant. 2009; 9: 2800-2807Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar) 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 (2Ruggenenti P Chiurchiu C Brusegan V et al.Rituximab in idiopathic membranous nephropathy: A one-year prospective study.J Am Soc Nephrol. 2003; 14: 1851-1857Crossref PubMed Scopus (201) Google Scholar). 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 (3Carson KR Evens AM Richey EA et al.Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: A report of 57 cases from the research on adverse drug events and reports project.Blood. 2009; 113: 4834-4840Crossref PubMed Scopus (781) Google Scholar). Conceivably, heavy immunosuppression plays a central role in the pathogenesis of these potentially fatal complications and avoiding unnecessary overexposure to lyxmphocytolytic 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 (4Ruggenenti P Cravedi P Remuzzi G Rituximab for membranous nephropathy and immune disease: Less might be enough.Nat Clin Pract Nephrol. 2009; 5: 76-77Crossref PubMed Scopus (17) Google Scholar). 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 (5Cravedi P Ruggenenti P Sghirlanzoni MC Remuzzi G Titrating rituximab to circulating B cells to optimize lymphocytolytic therapy in idiopathic membranous nephropathy.Clin J Am Soc Nephrol. 2007; 2: 932-937Crossref PubMed Scopus (140) Google Scholar). 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 (1El-Zoghby ZM Grande JP Fraile MG et al.Recurrent idiopathic membranous nephropathy: Early diagnosis by protocol biopsies and treatment with anti-CD20 monoclonal antibodies.Am J Transplant. 2009; 9: 2800-2807Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar) 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.