Rituximab vs. cyclophosphamide in treatment-naive IMN: efficacy and renal protection in early renal impairment

Abstract Background Cyclophosphamide (CTX) combined with glucocorticoids and rituximab (RTX) are widely used for idiopathic membranous nephropathy (IMN), but clinical data comparing them in newly diagnosed patients with impaired renal function (eGFR < 60 mL/min/1.73 m 2 ) remain scarce. This study aimed to compare their efficacy, safety, and effects on renal function in this specific population. Methods A retrospective study was conducted at the First Affiliated Hospital of Wannan Medical University from November 2019 to July 2024, including 113 newly diagnosed IMN patients (55 in the CTX group, 58 in the RTX group) diagnosed by renal biopsy or positive PLA2R antibodies. All patients were treatment-naive and followed for ≥ 6 months. Results At 6 months, composite remission rates were 69.09% in the CTX group and 62.07% in the RTX group ( P > 0.05). At 12 months, the RTX group showed a numerically higher composite remission rate (83.87% vs. 70.83% in CTX group) without statistical significance ( P = 0.186). By 18 months, both groups reached 73.68% composite remission ( P = 1.000). In the subgroup with eGFR < 60 mL/min/1.73 m 2 , RTX significantly improved renal function at 6 months ( P = 0.008), while CTX showed no significant improvement ( P = 0.113); however, no intergroup difference in eGFR was observed ( P = 0.793). The CTX group had a higher incidence of non-serious adverse events, including leukopenia and mild infections ( P < 0.05). HypoIgGemia was documented in 5 patients (8.62%) in the RTX group, all mild and asymptomatic. Conclusion RTX shows comparable efficacy and better safety relative to CTX in this cohort, and may be a preferred option for newly diagnosed untreated IMN, especially in those with early renal impairment. RTX demonstrated comparable efficacy to CTX in newly diagnosed IMN but with superior safety. Notably, RTX showed greater short-term (6-month) renal function improvement in patients with early renal impairment, though long-term effects need further verification in larger-sample prospective studies.