Latent Pathogen Reactivation During Six-Monthly Rituximab Therapy in Children with Idiopathic Nephrotic Syndrome: A Retrospective Cohort Study

Background Six-monthly rituximab therapy is increasingly used to maintain remission in children with idiopathic nephrotic syndrome. Data on infection safety, particularly patterns of latent pathogen reactivation, remain 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 collected from 12 months before to 24 months after treatment. Infection events and pathogen status were independently adjudicated by infectious disease specialists. Results During follow-up, no cases of clinically overt Epstein–Barr virus, cytomegalovirus, hepatitis B virus, or tuberculosis infection were observed. Transient and clinically silent changes in latent infection markers occurred without progression to active disease. Two patients (1.8%) developed invasive fungal pneumonia caused by Pneumocystis jirovecii or Candida albicans , both in the setting of concomitant immunosuppressive therapy. Within 12 months after rituximab initiation, 22 children (20%) experienced common infections, predominantly involving the respiratory tract. The most frequently identified pathogens were Streptococcus pneumoniae and influenza virus. In exploratory multivariable analyses, female sex and steroid-resistant nephrotic syndrome were associated with a higher risk of infection. Rituximab-associated B-cell depletion and reductions in immunoglobulin G were reversible over time, and liver and kidney function remained stable. Conclusions In this single-center cohort, a fixed six-monthly rituximab regimen was not associated with clinically significant activation of latent viral or mycobacterial infections under systematic monitoring. Respiratory infections and invasive fungal disease, particularly in the presence of concomitant immunosuppression, remain important clinical considerations.