1.Efficacy and prognostic analysis of rituximab in the treatment of M-type phospholipase A2 receptor-associated idiopathic membranous nephropathy
Jia CHEN ; Haofei HU ; Yuan CHENG ; Dongli QI ; Mijie GUAN ; Guobao WANG ; Qijun WAN
Chinese Journal of Nephrology 2024;40(8):628-636
Objective:To investigate the efficacy and prognosis of rituximab (RTX) in the treatment of M-type phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN).Methods:It was a retrospective cohort study. The clinical data of PLA2R-associated IMN patients who received RTX treatment in the Shenzhen Second People's Hospital from September 2018 to March 2023 were collected. According to remission status of proteinuria, the patients were divided into proteinuria remission group (24-hour urinary protein quantity < 3.5 g) and non-proteinuria remission group (24-hour urinary protein quantity ≥ 3.5 g), and the clinical data between the two groups were compared. According to baseline 24-hour urinary protein quantity and estimated glomerular filtration rate (eGFR), the patients were divided into high-risk disease progression group [24-hour urinary protein quantity ≥ 8 g or eGFR < 60 ml·min -1·(1.73 m 2) -1] and non-high-risk disease progression group [24-hour urinary protein quantity < 8 g or eGFR ≥ 60 ml·min -1·(1.73 m 2) -1]. Kaplan-Meier survival curve was utilized to compare the differences of proteinuria remission rates and renal composite endpoint event survival rates between the two groups. Multivariate Cox regression analysis was utilized to identify the influencing factors of proteinuria remission and renal composite endpoint event. Results:This study included 46 PLA2R-associated IMN patients, with 31 males (67.4%). The baseline eGFR was (78.4±34.1) ml·min -1·(1.73 m 2) -1. The 24-hour urinary protein quantity was 8.33 (6.04, 12.85) g. After 14.95 (7.44, 22.15) months of follow-up, 29 patients (63.0%) achieved proteinuria remission, with remission time of 6.0 (5.0, 9.0) months. Six (20.7%) patients relapsed, with relapsed time of 17.25 (11.75, 18.28) months. CD20 in the proteinuria remission group was lower than that in the non-proteinuria remission group ( Z=2.270, P=0.023). Eleven (23.9%) patients experienced renal composite endpoint events wtih occurrence time of 16.07 (7.87, 29.63) months. Kaplan-Meier survival curve analysis indicated that there was no statistically significant difference in proteinuria remission rates (log-rank χ2=0.26, P=0.612) and renal composite endpoint event survival rates (log-rank χ2=0.25, P=0.619) between baseline 24-hour urinary protein quantity ≥ 8 g and < 8 g groups. There was no statistically significant difference in proteinuria remission rates after RTX treatment (log-rank χ2=0.77, P=0.381) and renal composite endpoint event survival rates (log-rank χ2=1.41, P=0.236) between eGFR ≥ 60 ml·min -1·(1.73 m 2) -1 and < 60 ml·min -1·(1.73 m 2) -1 groups. Multivariate Cox regression analysis showed that hypertension history ( HR=0.16, 95% CI 0.05-0.55), immunosuppressive therapy history ( HR=0.08, 95% CI 0.01-0.50), baseline eGFR < 60 ml·min -1·(1.73 m 2) -1 ( HR=0.21, 95% CI 0.05-0.92), baseline PLA2R antibody titer ≥ 100 RU/ml ( HR=0.20, 95% CI 0.06-0.69), long time between treatment and first diagnosis ( HR=1.33, 95% CI 1.12-1.57), high baseline triglyceride ( HR=1.46, 95% CI 1.02-2.08), and baseline 24-hour urinary protein quantity ≥ 8 g ( HR=8.54, 95% CI 2.08-35.12) were independent influencing factors of proteinuria remission after RTX treatment. The baseline PLA2R antibody titer ≥ 100 RU/ml was an independent influencing factor of reaching the renal composite endpoint event ( HR=7.31, 95% CI 1.23-43.62). Conclusions:The proteinuria remission rate after RTX treatment of PLA2R-associated IMN is 63.0% and the recurrence rate is 20.7%. The incidence rate of renal composite endpoint event is 23.9%. The hypertension history, immunosuppressant medication history, baseline eGFR < 60 ml·min -1·(1.73 m 2) -1, baseline PLA2R antibody titer ≥ 100 RU/ml, long time between treatment and first diagnosis, high baseline triglyceride, and baseline 24-hour urinary protein quantity ≥ 8 g are independent influencing factors of proteinuria remission, and baseline PLA2R antibody titer ≥ 100 RU/ml is an independent risk factor of renal poor prognosis in PLA2R-associated IMN patients.