Risk factors and retreatment for relapse in childhood primary nephrotic syndrome treated with rituximab.

Background: The effectiveness of rituximab (RTX) for steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) in children is well documented. However, there are insufficient data on relapse risk factors. Additionally, the retreat regimen for relapsed children requires further investigation.

Methods: We administered single dose RTX (375 mg/m2, maximum 500 mg) to children with SDNS/FRNS between May 2020 and December 2022. An additional single dose of RTX was administered when B-cell depletion (CD19 + B cells < 1%) was incomplete or B-cell recovery (CD19 + B cells ≥ 1%) occurred. Primary and secondary outcomes were the first and second relapse, respectively.

Results: Eighty-nine patients were included and the observation period was 12.2-43.2 months. Thirty-three patients (37.1%) relapsed after RTX treatment. Multivariate analysis showed that previous steroid-resistant nephrotic syndrome (SRNS) history and low NK-cell percentage at initial RTX treatment were independent risk factors for first relapse. In the relapse group, 26 patients (78.8%) continued RTX treatment upon B-cell recovery. During mean follow-up period of (15.4 ± 8.1) months, 15 patients (45.5%) experienced a second relapse. Compared with non-continued RTX treatment group, the continued RTX treatment group had a lower relapse rate (34.6% (9/26) versus 85.7% (6/7); P = 0.047) and fewer relapses (0.0 (0.0, 0.6) versus 1.8 (0.9, 2.7) times/year; P = 0.004). Multivariate analysis showed that continued RTX treatment was the protective factor for second relapse.

Conclusions: Previous SRNS history and low NK-cell percentage at initial RTX treatment may be associated with higher risk of relapse. Despite the possibility of relapse during RTX treatment, continued RTX treatment is effective in reducing relapse.