Zijian Zhou,1,* Yijing Zou,1,* Ben Ke,2,3 Wen Shen4 

1The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Jiangxi Province Key Laboratory of Immunology and Inflammation, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang, Jiangxi, People’s Republic of China; 4Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Ben Ke, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, People’s Republic of China, Tel +8615270882765, Email keben-1989125@163.com Wen Shen, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, People’s Republic of China, +8618146622197, Email 18146622197@163.com

Background: Cyclophosphamide, tacrolimus, and rituximab (RTX) are first-line treatments for idiopathic membranous nephropathy (IMN), regardless of PLA2R status. While the efficacy of RTX in IMN patients with PLA2R-positive has been well-documented, its effectiveness in IMN patients with PLA2R-negative remains understudied. This study aimed to evaluate the efficacy and adverse events of these three treatment regimens in IMN patients with PLA2R-negative.
Methods: This study included 46 PLA2R-negative IMN patients confirmed by renal biopsy and immunofluorescence from the Department of Nephrology, the Second Affiliated Hospital of Nanchang University between September 2021 and October 2023. We compared clinical remission rates, and side effects at 3, 6, and 12 months follow-up in 14 patients who received prednisolone combined with cyclophosphamide (cyclophosphamide group), in 11 patients who treated with prednisolone combined with tacrolimus (tacrolimus group), and 21 patients who treated with rituximab (RTX group).
Results: Baseline characteristics were similar among the three groups. At the 12-month follow-up, the complete response rate was significantly higher in the cyclophosphamide and tacrolimus groups compared to the RTX group (p = 0.029). However, there were no significant differences in cumulative complete remission rates or cumulative composite remission rates among the three groups during the follow-up period (p = 0.192, p = 0.212). Severe adverse events occurred in all groups, but the differences were not statistically significant (p > 0.05).
Conclusion: Cyclophosphamide and tacrolimus appear to offer long-term benefits for PLA2R-negative IMN patients, with tacrolimus demonstrating superior efficacy among the treatment options evaluated. These insights offer important guidance for clinical decision-making in the management of PLA2R-negative IMN. However, further large-scale, multicenter studies with long-term follow-up are necessary to confirm these findings.

Keywords: idiopathic membranous nephropathy, PLA2R-negative, cyclophosphamide, tacrolimus, rituximab