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

BackgroundThe 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. MethodsWe 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. ResultsEighty-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. ConclusionPrevious 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. Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information