The efficacy and dynamic changes of immune function of rituximab with mycophenolate mofetil in the treatment of steroid-dependent /frequently relapsing nephrotic syndrome: a retrospective follow-up study.

Background: Approximately 70%～90% of children with steroid-sensitive nephrotic syndrome (SSNS) will suffer from steroid dependency or frequent relapses, prompting the use of steroid-sparing agent. In this study, we investigate the efficacy and the characteristics of dynamic changes in immune function of two doses of rituximab (RTX) in the treatment of steroid-dependent/frequently relapsing nephrotic syndrome (SDNS /FRNS).

Methods: Retrospective follow-up study was conducted in our hospital from June 2022 to September 2023. 7 children with SDNS /FRNS were allocated to intravenous 2 doses RTX (each dose 375mg/m2, 1 dose per week) and administered the standard oral dose of mycophenolate mofetil (MMF) (1000-1200/m2/d, divided into 2 doses) when B cells have recovered (≥ 5/ul). The study subjects after treatment were monitored for the efficacy and dynamic changes of immune function for 12 months.

Results: 7 children with SDNS/FRNS who were treated RTX with MMF and followed up for 12 months have no relapse. The rate of B cell depletion (< 5/ul) was 100% at 1 week after the second dose of RTX treatment, and the rate of B cell recovery was 100% at 5-12 months after the first dose of RTX treatment. There was no significant difference with T cell subsets (CD3, CD4, CD8, CD4/CD8) at each follow-up time points (all P > 0.05). The count of NK cells was significantly higher than that of other groups at 1 week after the second dose (P < 0.05). The IgM level at 1 week after the second dose was significantly lower than that before treatment and 1 week after the first dose (P < 0.05). There were no significant differences with IgA, IgG, C3 and C4 before treatment, 1 week after the first dose and 1 week after the second dose (all P > 0.05).

Conclusions: Administering two doses of RTX along with the standard dose of MMF has been effective in maintaining remission for children with SDNS/FRNS. B cell depletion can be achieved one week after the second dose of RTX treatment. NK cell proliferation may play a role in B cell depletion, and early B cell depletion may suppress the production of IgM. These findings require further validation through additional clinical trials and basic research.