Low-dose rituximab for refractory idiopathic membranous nephropathy: A retrospective study

Abstract Background The efficacy of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN) has been confirmed, but the specific dosing regimens have not been standardized. The aim of this study was to investigate the clinical efficacy and safety of low-dose rituximab (RTX) for the treatment of refractory IMN. Methods Data from 24 refractory IMN patients who received low-dose RTX treatment at our hospital between October 2018 and November 2021 were retrospectively analysed, and biochemical data at different time points were compared. Results The patients were predominantly male (n = 17) and had a mean age of 52.17 ± 8.28 years, a mean eGFR of 82.59 ± 26.26 mL/min/1.73 m2, a serum albumin (ALB) level of 20.4 ± 4.36 g/L, a urine protein-to-creatinine ratio (UPCR) of 9.53 g/g (interquartile range [IQR], 5.89 to 11.07), and a CD19 B-cell count at baseline of 296.83 ± 114.34/µL. Twenty-two patients were positive for the anti-phospholipase A2 receptor (PLA2R) antibody. After 12 months of RTX treatment, the serum ALB concentration increased by 8.03 ± 7.21 g/L compared with that at baseline (P < 0.05), and the UPCR decreased by 2.13 ± 4.82 g/g compared to that at baseline (P < 0.05). When the serum ALB concentration increased significantly, the UPCR decreased significantly, and the serum creatinine did not change significantly at different time points at 12 months. At a median follow-up of 28 months (IQR, 18 to 43), four patients achieved complete remission (CR), eleven patients achieved partial remission (PR), and one patient needed dialysis. The anti-PLA2R antibody status changed from positive to negative in 14 (58.3%) patients within a median of 9 (IQR, 5 to 22) months, and 13 (92.9%) patients achieved CR (3 patients) or partial response (PR) (10 patients). Among the 8 patients whose anti-PLA2R antibody status was persistently positive, only 1 (12.5%) patient achieved a PR. There was a significant difference in clinical remission between patients with and without a change in anti-PLA2R antibody status from positive to negative (P < 0.001). During RTX treatment, infusion reactions occurred in two patients, and nonsevere infections (pulmonary, skin and urinary tract infections) occurred in five patients. Treatment was discontinued in one patient due to severe pneumonia. Conclusion Low-dose RTX can induce clinical and immunological remission in refractory IMN patients. Despite the prolonged duration of remission, a remission rate of 62.5% was achieved during the 2-year follow-up period.