Rituximab Administration in Pediatric Glomerulopathies Amid Challenging Circumstances: Insights from Clinical Experience

Abstract

Abstract Background: The ISN Green Nephrology Initiative, coupled with limited capacity in low-middle-income countries and the challenges posed by military conflicts, necessitates innovative solutions in pediatric nephrology for optimizing the treatment of children with kidney diseases. This study aims to assess the effectiveness and safety of Rituximab (RTX) usage in children with glomerular diseases, with an extension of clinical indications.Methods: We initiated an ongoing open-label, multicenter, randomized, patient-oriented study, termed RIME ("RTX in glomerulopathies"), focusing on children with glomerulopathies in Ukraine during martial law (enrolled 2022–2023). Inclusion criteria comprised patients with steroid-dependent (SDNS) or frequently relapsing nephrotic syndrome (FRNS) and progressive glomerulopathies, as determined by eGFR (estimated glomerular filtration rate), ACR (albumin-to-creatinine ratio), and kidney biopsy results. RTX was explored as an alternative to glucocorticoid re-administration and a potential treatment to decelerate renal function decline. The primary endpoint was eGFR and ACR up to 6 months from RTX initiation, with the secondary endpoint assessing the delayed effect at 1 year.Results: As of November 2023, results were available for 19 children, including 7 with FRNS and 12 with progressive loss of renal function and/or increased ACR. RTX use resulted in stable remission of steroid-dependent FRNS, with statistically significant urinalysis normalization and hyperfiltration by the 6th month, leading to eGFR normalization within a year. RTX demonstrated a 75% success rate in achieving a stable trend in reducing ACR and restoring eGFR in progressive glomerulopaties. In this group, stable trends did not receive statistically significant changes, which is obviously due to the small size of the sample. Tolerability was observed in 80% of patients, allowing completion of the full course of therapy.Conclusions: RTX, if tolerated, proved highly effective as a steroid-sparing agent and demonstrated efficiency in slowing the pathological process in progressive glomerulopathies, indicating the potential for ACR reduction and renal function restoration. Future studies should assess the balance between treatment cost, convenience, adherence to Green Nephrology principles, and the feasibility of a virtual nephrology approach in conflict zones.