Correspondence
Rituximab in Patients with the Steroid-Resistant Nephrotic Syndrome
N Engl J Med 2007; 356:2751-2752June 28, 2007
- Article
To the Editor:
The treatment of patients with the steroid-resistant nephrotic syndrome (SRNS) is challenging. Persistent proteinuria and hypoalbuminemia result in serious complications and progressive kidney disease. Intensive treatment regimens show varying results in inducing remission but are associated with adverse effects. On the basis of suggestions that B lymphocytes are crucial in the pathogenesis of the nephrotic syndrome,1 we examined the efficacy of treatment with rituximab, a monoclonal antibody against CD20 antigen, in patients with SRNS that was resistant to treatment with high-dose corticosteroids, alkylating agents, and calcineurin inhibitors.
Five patients (three with initial resistance and two with late resistance to corticosteroids) between the ages of 2.8 and 16.0 years were included in our study. Renal-biopsy specimens showed minimal-change disease in two of the patients and focal segmental glomerulosclerosis in three. The children had previously received multiple medications for 1.8 to 14.2 years, with periods of partial or complete remission (Table 1Table 1
Characteristics of the Five Patients and Their Response to Treatment with Rituximab.). All had SRNS and were resistant to standard medications, including 6 months of recent treatment with calcineurin inhibitors.After receiving approval from the ethics committee at our institution and parental consent, we administered rituximab by intravenous infusion at a dose of 375 mg per square meter of body-surface area once weekly for 4 weeks; the patients continued to receive therapy with calcineurin inhibitors, alternate-day prednisolone, or both. During treatment with rituximab, the patients received cotrimoxazole prophylaxis for 6 months. Reduction in proteinuria, as measured by a dipstick test of the ratio of urinary protein to creatinine, was noted after the infusions. At a median interval of 4 weeks (range, 2 to 8) after the last rituximab dose, four patients had a complete remission (urinary albumin, trace/negative), and one patient had a partial remission (urinary albumin, 2+). Six months later, one patient had a relapse and was treated with prednisolone, which resulted in a partial response. Complete remission was maintained in three patients, despite the tapering of doses of corticosteroids and calcineurin inhibitors (Table 1). The mean ratio of urinary protein to creatinine was 8.3 at baseline and 0.8 at follow-up (P=0.02, by analysis of variance), the mean serum albumin level rose from 1.4 to 3.4 g per deciliter (P<0.01), and the mean cholesterol level declined from 481 to 260 mg per deciliter (P<0.05); differences in leukocyte counts and levels of IgG were not significant, and none of the patients had serious infections.
Rituximab is reported to induce remission of proteinuria in patients with steroid-sensitive nephrotic syndrome2-4 and recurrent focal segmental glomerulosclerosis in allografts.5 We report on the efficacy of the drug in inducing remission in patients with steroid-sensitive nephrotic syndrome. Proteinuria abated after treatment, and remission was sustained on follow-up. Therapy with rituximab appears to be promising in patients with SRNS. However, there is recent concern regarding viral reactivation and progressive multifocal leukoencephalopathy in patients with lupus erythematosus who receive this drug (www.fda.gov/medwatch/safety/2006/safety06.htm#rituxan). Further studies are necessary to define the efficacy and safety of rituximab in patients with SRNS.
Arvind Bagga, M.D.
Aditi Sinha, M.D.
All India Institute of Medical Sciences, New Delhi 110029, India
arvindbagga@hotmail.com Asha Moudgil, M.D.
Children's National Medical Center, Washington, DC 20010Supported in part by funding from Roche India.
No potential conflict of interest relevant to this letter was reported.
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