Effect of Single-Dose Rituximab on Primary Glomerular Diseases

Abstract

Background: A paradigm shift from such toxic ‘nonspecific’ therapies to selective immunomodulating regimens is necessary for glomerular diseases. Rituximab, which acts by inhibiting CD20-mediated B cell proliferation and differentiation, could be effective in the treatment of nephrotic syndrome as shown in recent reports. Design: To assess the effects of rituximab in patients with primary glomerular diseases, including minimal-change disease, immunoglobulin A (IgA) nephropathy, focal segmental glomerulonephritis, membranous nephropathy and membranoproliferative glomerulonephritis, we performed a prospective trial of the effects of single-dose rituximab therapy in 24 patients. We prospectively evaluated the serum and urinary biochemical parameters before and after 6 months of therapy. Results: In all of the patients studied, depletion of CD19 and CD20 cells was noted, with significant reduction in the degree of proteinuria from 3.7 ± 3.4 g/day at baseline to 1.3 ± 2.0 g/day at 6 months after the drug administration (p = 0.002). However, no significant changes of the serum creatinine, urinary RBC sediment, serum CD4/8 or serum IL-4 levels were observed at 6 months after the drug administration. In subjects with IgA nephropathy, while depletion of CD19 and CD20 cells was noted, no significant change in the severity of proteinuria was observed at 6 months after the drug administration as compared with the level at the baseline. Conclusion: For the treatment of primary glomerular diseases, the use of a single dose of rituximab is demonstrated with no serious adverse events. Further study of the mechanism of action of rituximab in successfully treated patients could encourage new perspectives in the treatment of primary glomerular diseases.

The Treatment of Minimal Change Disease in Adults

“…[69][70][71][72][73][74][75][76][77][78][79] These studies indicate that response to treatment is associated with peripheral B cell depletion.…”

American Society of Nephrology Quiz and Questionnaire 2013

“…These initial findings were corroborated by a number of other case reports and retrospective and prospective studies (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Rituximab generally induced sustained remission allowing for a marked reduction or discontinuation of corticosteroids and/or immunosuppressive drugs in patients with MCD who were steroid dependent or frequent relapsers (24).…”

“…Losartan 50 mg/d, orally B. Prednisone 1 mg/kg per day, orally for .4 months C. Cyclosporine 3.5-5 mg/kg per day orally, with trough blood levels of 125-175 ng/ml D. MMF 1g, orally, twice a day E. Sirolimus 5 mg/d, orally, with trough blood levels [12][13][14][15][16][17][18][19][20] ng/ml Discussion of Case 2, Question 2B In this patient, the absence of NS and focal foot process effacement on EM makes FSGS most likely to be secondary and should be treated conservatively, aiming to control BP and reduce proteinuria using inhibitors of the reninangiotensin system rather than immunosuppressive therapy. For this reason, treatment with losartan is the most appropriate of the options given (choice A is correct) ( Figure 5).…”

Is it the time to offer rituximab as a cost-benefit treatment for immunoglobulin A nephropathy? A short-review to current concepts

“…However, Sugiura et al (19) did not find any proteinuria reduction after singledose rituximab in five non-nephrotic IgAN patients.…”