Risk Factors for Rituximab Dependency in Pediatric and Young-Adult Patients with Refractory Nephrotic Syndrome

Background: Rituximab (RTX) has been shown to be effective for childhood-onset refractory nephrotic syndrome and is being administered worldwide. While steroid discontinuation is possible in many patients after RTX, a certain number of patients cannot be weaned from RTX administration due to relapses of nephrotic syndrome after B cell recovery. Methods: this is a single-center, retrospective study. Twenty-five patients with refractory nephrotic syndrome who received RTX at our department from January 2011 to November 2021 were recruited in this study. They were divided into two groups; a group that could not be weaned from RTX administration (group A) and a group that could be controlled without RTX for more than two years (group B). Results: There were 10 patients in group A (male:female = 7:3) and 15 patients in group B (male:female = 7:8). The patients in group A had a significantly higher age at first RTX administration than the patients in group B (12±4.0; 7.8±3.7 years, p<0.05), and a longer period from the onset of nephrotic syndrome to RTX administration (8.1±4.0; 4.1± 3.2, year, p<0.05). The IgG level at the first administration was significantly higher in group A (708.8±220.0; 467.2±263.6, mg/dL, p<0.05), perhaps due to the older age of the patients, but the IgG levels at the final examination were not significantly different between the two groups (649.5±244.7; 723.8±337.2, mg/dL, p=0.59). There was no significant difference in age at onset between the two groups (3.9±1.7; 3.7±3.3 years, p=0.82). Conclusion: The rate of RTX dependence was as high as 40% in our hospital. The age at the first RTX administration was higher in the dependent group (group A), suggesting a relationship between the immunological developmental process and the efficacy and sensitivity of RTX. Because side effects of long-term use of RTX have not been fully understood, we should be cautious in maintaining therapy with RTX. Limitations were; 1) the number of patients who were analyzed in this study was small; 2) the preference of RTX was affected by other factors due to the fact that RTX has few side effects regarding blood pressure, blood glucose level or physical appearance, with the exception of infusion reactions and various kinds of immunological deficits. Funding: Government Support – Non-U.S.