Rituximab-Based Therapy in IgA Nephropathy With Crescents: A Comparative Study.

PURPOSE: IgA nephropathy with crescents (c-IgAN) is frequently underrepresented in randomized trials. We assessed whether rituximab (RTX) plus corticosteroids (CS) improves outcomes compared with a histology-matched cohort receiving standard high-dose CS (Pozzi protocol). METHODS: We conducted a single-center retrospective comparative study in adults with biopsy-proven c-IgAN diagnosed between January 2017 and December 2024. Outcomes of 16 patients treated with RTX (1 g × 2, 14 days apart) plus CS (three 500 mg pulses followed by 1 mg/kg tapered over 4 months) were compared with eight patients treated with Pozzi's protocol. Primary endpoints were changes in 24-h proteinuria, estimated glomerular filtration rate (eGFR), and microscopic hematuria at 6, 12, and 24 months, and annual eGFR slope. Secondary endpoints included remission rates, relapse risk, and adverse events (AEs). Longitudinal analyses were performed using mixed-effects models. FINDINGS: At baseline, median age was 35.5 years, eGFR was 69 mL/min/1.73 m² with a recent eGFR decline of -15.8 mL/min/1.73 m² over 3 months, median proteinuria was 1.8 g/day, all patients had microscopic hematuria. Proteinuria reduction was greater in RTX group than Pozzi's protocol (P = 0.0065), with an -85.6% between-group difference at 24 months (P = 0.0049). eGFR changes were similar (P = 0.27), although annual slope favored RTX (+5.10 vs -8.01 mL/min/1.73 m²/year). Microscopic hematuria improved in both groups. RTX was associated with lower relapse risk (odds ratio 0.14; 95% CI 0.01-1.00; P = 0.06). AEs were comparable. IMPLICATIONS: In this real-life cohort of c-IgAN, RTX and CS combination was associated with greater proteinuria reduction and sustained proteinuria control and fewer relapses compared with high-dose CS regimen, without difference in renal function or safety. The retrospective design and limited sample size warrant confirmation in prospective studies.