Efficacy and safety of scheduled rituximab in children with refractory nephrotic syndrome after multi-target therapy failure

TL;DR

Rituximab maintenance therapy significantly reduced relapses and allowed medication reduction in children with refractory nephrotic syndrome who failed multiple treatments.

Contribution

Demonstrates the efficacy and safety of scheduled rituximab in multi-target therapy–refractory pediatric nephrotic syndrome.

Findings

Annual relapse rate dropped from 2.1 to 0.2 after rituximab treatment.

85% of patients discontinued steroids, and 73% stopped all other immunosuppressants.

No patients progressed to kidney failure over 2.5 years of follow-up.

Abstract

Children with refractory nephrotic syndrome (NS) often experience frequent relapses despite combination immunosuppressive therapy. This study evaluated the efficacy and safety of scheduled rituximab (RTX) maintenance therapy in children with refractory NS who failed multi-target therapy.

We retrospectively analyzed 48 children under 18 years old with steroid-dependent or steroid-resistant NS who had ≥ 2 relapses within 6 months despite corticosteroids plus at least two other immunosuppressants (multi-target therapy failure). Relapse rates before and after RTX, medication reduction, adverse events, and kidney outcomes were assessed.

Of 51 patients treated, 48 met inclusion criteria (three excluded for severe infusion reactions or loss to follow-up). RTX maintenance therapy significantly reduced the annual relapse rate from a mean of 2.1 relapses/year before RTX to 0.2 relapses/year after RTX (p < 0.0001). Over half of patients (56%) remained completely relapse-free during RTX treatment. Corticosteroids were successfully discontinued in 85% of patients (median 1 year after RTX), and all other immunosuppressants were stopped in 73% (median 0.8 years). Overall, 69% of patients were able to discontinue steroids plus two immunosuppressive drugs, maintaining remission on RTX alone. Adverse events were mostly mild: 56% had asymptomatic hypogammaglobulinemia, 8% experienced transient neutropenia (no agranulocytosis), 4% had mild infections, and 4% had infusion reactions (rash or throat discomfort) that resolved with supportive care. No patient progressed to kidney failure over a median follow-up of 2.5 years.

Scheduled RTX maintenance therapy effectively maintained remission in children with multi-target therapy–refractory NS, allowing substantial reduction or cessation of steroids and other immunosuppressants.

A higher resolution version of the Graphical abstract is available as Supplementary information

A higher resolution version of the Graphical abstract is available as Supplementary information

The online version contains supplementary material available at 10.1007/s00467-025-07069-6.

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