Effect of single-dose rituximab on primary glomerular diseases.
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.


METHODS
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.


CONCLUSIONS
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.
Sugiura
Hidekazu
H
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Takei
Takashi
T
Itabashi
Mitsuyo
M
Tsukada
Misao
M
Moriyama
Takahito
T
Kojima
Chiari
C
Shiohira
Toshiharu
T
Shimizu
Ari
A
Tsuruta
Yuki
Y
Amemiya
Nobuyuki
N
Ogawa
Tetsuya
T
Uchida
Keiko
K
Tsuchiya
Ken
K
Nitta
Kosaku
K
D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005921:Glomerulonephritis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab