Rituximab treatment combined with methylprednisolone pulse therapy and immunosuppressants for childhood steroid-resistant nephrotic syndrome.
BACKGROUND
Calcineurin inhibitors (CIs) with/without intravenous methylprednisolone pulse therapy (MPT) constitute the standard treatment for childhood-onset, steroid-resistant nephrotic syndrome (SRNS). However, some patients fail to achieve remission. We treated SRNS patients resistant to CIs and MPT with additional rituximab combined with MPT and immunosuppressive agents.


METHODS
Ten patients (aged 2-14 years) with CI- and MPT-resistant SRNS were enrolled. Patients were administered rituximab (1-4 doses; 375 mg/m(2)) followed by MPT (30 mg/kg/day of methylprednisolone for 3 consecutive days) once every 2-4 weeks until complete remission (CR). We analyzed clinical outcome and safety.


RESULTS
Six patients received a single dose of rituximab, 2 received two doses, and 2 received four doses. Seven patients achieved CR, 1 achieved partial remission, and 2 showed no response. Although 2 patients with no response progressed to end-stage renal failure, 7 patients with CR preserved normal renal function without proteinuria at the last observation. There were two serious adverse events.


CONCLUSIONS
Additional rituximab combined with conventional MPT and immunosuppressive agents is a promising option for overcoming refractory SRNS. Aggressive B cell suppression by rituximab may ameliorate resistance to conventional treatments and a cocktail of other immunosuppressive agents, such as CIs, MMF, mizoribine, may be beneficial. However, as intense immunosuppression may cause serious adverse events, further evaluation is necessary.
Department of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan, kamei-k@ncchd.go.jp.
Koichi
K
Kamei
Mari
M
Okada
Mai
M
Sato
Takuya
T
Fujimaru
Masao
M
Ogura
Makiko
M
Nakayama
Hiroshi
H
Kaito
Kazumoto
K
Iijima
Shuichi
S
Ito
D000293:Adolescent; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D011379:Prognosis; D000069283:Rituximab
D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D000069283:Rituximab; D008775:Methylprednisolone