Risk of Reactivation of Latent Pathogens Associated with Six-Monthly Rituximab Therapy in Children with Nephrotic Syndrome: A Retrospective Cohort Study

Background Six-monthly rituximab therapy is increasingly used to maintain remission in children with idiopathic nephrotic syndrome, but evidence regarding infection safety and latent pathogen reactivation remains limited. Methods In this retrospective, self-controlled study, 110 children with idiopathic nephrotic syndrome received rituximab (375 mg/m²) every six months. Clinical and laboratory data were analyzed from 12 months before to 24 months after treatment. Infection events were independently reviewed by infectious disease specialists. Results No episodes of active Epstein Barr virus, cytomegalovirus, hepatitis B virus or tuberculosis infection occurred during follow-up. Transient, self-limited reactivations were observed without clinical progression. Two patients (1.8%) developed invasive fungal pneumonia (Pneumocystis jirovecii, Candida albicans) under concomitant immunosuppression. Within 12 months, 22 children (20%) developed mostly respiratory infections, commonly Streptococcus pneumoniae and influenza virus. Female sex and steroid-resistant nephrotic syndrome were independent risk factors. Rituximab induced B-cell depletion and immunoglobulin G reduction were reversible, with stable liver and kidney function. Conclusions In children with idiopathic nephrotic syndrome, the six-monthly rituximab regimen did not show evidence of increased activation of latent pathogens under systematic monitoring. Respiratory and fungal infections under concomitant immunosuppression remain a clinical concern. These findings offer real-world evidence to support current rituximab guidelines and may inform globally applicable strategies for infection monitoring, prophylaxis, and vaccination in children receiving biologic therapy.