Identification of Risk Factors for Relapse following Rituximab Therapy in Children with Steroid-Sensitive Nephrotic...

Rituximab (RTX) is a key therapeutic agent for maintaining remission in steroid-dependent nephrotic syndrome and frequently relapsing nephrotic syndrome, demonstrating both efficacy and safety. However, reliable biomarkers for predicting relapse remain under investigation.

This single-center, retrospective, observational study included 70 patients who received RTX between January 2015 and January 2023. Patients were classified into two groups: the non-relapse group and the relapse group. Cox proportional hazards regression was used to analyze the associations between baseline clinical parameters and relapse risk, while Kaplan-Meier survival analysis was performed to estimate the recurrence-free survival rates.

This cohort of 70 pediatric patients (71.4% male; median age: 9.5 years, interquartile range: 8.5-12.6) exhibited a 24-month post-rituximab relapse rate of 32.9% (23/70). Multivariate analysis identified elevated baseline memory B-cell levels (adjusted hazard ratio [HR] = 1.103, 95% confidence interval [CI]: 1.045-1.164, p < 0.001), reduced baseline natural killer (NK) cell levels (adjusted HR = 0.866, 95% CI: 0.752-0.997, p = 0.045), and higher IgG levels at 3 months post-RTX (adjusted HR = 1.245, 95% CI: 1.080-1.435, p = 0.003) as independent predictors of relapse. Kaplan-Meier survival analysis revealed that patients with memory B-cell counts below 19.65% of baseline (n = 38) had significantly higher 24-month relapse-free survival compared to those with counts above this threshold (n = 32; 86.8% vs. 43.8%; χ² = 13.918, p < 0.001). In contrast, patients with NK-cell levels below 6.45% of lymphocytes (n = 25) exhibited poorer 24-month relapse-free survival than those with higher NK-cell proportions (n = 45; 52.0% vs. 77.8%; χ² = 6.395, p = 0.011). Similarly, patients with IgG levels below 5.74 g/L (n = 35) demonstrated significantly better relapse-free survival compared to those with higher levels (n = 35; 85.3% vs. 47.2%; χ² = 11.030, p = 0.001).

Baseline memory B-cell and NK-cell levels (pre-RTX), as well as IgG levels at 3 months post-RTX, were identified as predictive biomarkers for the 2-year relapse risk following RTX therapy. These findings may contribute to the development of personalized RTX treatment strategies.