Xin Wang1,2,3,4, Zhao Cui1,2,3,4, Yi-Miao Zhang1,2,3,4, Zhen Qu1,2,3,4, Fang Wang1,2,3,4, Li-Qiang Meng1,2,3,4, Xu-Yang Cheng1,2,3,4, Gang Liu1,2,3,4, Fu-de Zhou1,2,3,4, Ming-Hui Zhao1,2,3,4,5. 1. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China. 2. Institute of Nephrology, Peking University, Beijing, China. 3. Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China. 4. Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China. 5. Peking-Tsinghua Center for Life Sciences, Beijing, China.
Abstract
Background: Rituximab had been shown to be effective in inducing remission of nephrotic syndrome in patients with idiopathic membranous nephropathy (iMN). This study applied rituximab therapy for 36 non-responsive iMN patients to investigate its effects and safety. Methods: Thirty-six iMN patients who were non-responsive to prior immunosuppression were enrolled. Rituximab was used for B-cell depletion in patients, with a goal of <5 B cells/mm3 in the circulation. After completing the study, patients were monitored for a median of 12.0 months [interquartile range (IQR) 9.0-19.3]. Results: Fifteen of the 36 (41.7%) patients achieved partial (n = 13) or complete (n = 2) response to the rituximab treatment. The median time for achieving partial response was 4.0 months (IQR 3.0-6.0). The responders had relatively lower levels (118 ± 112 U/mL versus 345 ± 357 U/mL, P = 0.03) of anti-phospholipase 2 receptor (PLA2R) antibodies before the rituximab treatment, and all of them achieved antibody depletion or reduction. B-cell depletion was achieved in all patients. Renal function remained stable in the responders [estimated glomerular filtration rate (eGFR) 53.3 ± 40.5 versus 55.6 ± 33.2 mL/min/1.73 m2, P = 0.67] but deteriorated in the non-responders (eGFR 57.5 ± 29.3 versus 45.3 ± 32.8 mL/min/1.73 m2, P = 0.02) with two patients reaching end-stage kidney disease. Two of the 15 patients relapsed during the follow-up period with anti-PLA2R antibody reoccurrence and B-cell reconstitution. The second course of rituximab combined with tacrolimus induced a faster partial response again in one patient. Conclusion: Rituximab therapy could induce remission of proteinuria and stabilization of renal function in non-responsive iMN patients, even those with damaged renal function. Anti-PLA2R antibodies may be used as a marker for individualized rituximab dosage and treatment monitoring.
Background: Rituximab had been shown to be effective in inducing remission of nephrotic syndrome in patients with idiopathic membranous nephropathy (iMN). This study applied rituximab therapy for 36 non-responsive iMN patients to investigate its effects and safety. Methods: Thirty-six iMN patients who were non-responsive to prior immunosuppression were enrolled. Rituximab was used for B-cell depletion in patients, with a goal of <5 B cells/mm3 in the circulation. After completing the study, patients were monitored for a median of 12.0 months [interquartile range (IQR) 9.0-19.3]. Results: Fifteen of the 36 (41.7%) patients achieved partial (n = 13) or complete (n = 2) response to the rituximab treatment. The median time for achieving partial response was 4.0 months (IQR 3.0-6.0). The responders had relatively lower levels (118 ± 112 U/mL versus 345 ± 357 U/mL, P = 0.03) of anti-phospholipase 2 receptor (PLA2R) antibodies before the rituximab treatment, and all of them achieved antibody depletion or reduction. B-cell depletion was achieved in all patients. Renal function remained stable in the responders [estimated glomerular filtration rate (eGFR) 53.3 ± 40.5 versus 55.6 ± 33.2 mL/min/1.73 m2, P = 0.67] but deteriorated in the non-responders (eGFR 57.5 ± 29.3 versus 45.3 ± 32.8 mL/min/1.73 m2, P = 0.02) with two patients reaching end-stage kidney disease. Two of the 15 patients relapsed during the follow-up period with anti-PLA2R antibody reoccurrence and B-cell reconstitution. The second course of rituximab combined with tacrolimus induced a faster partial response again in one patient. Conclusion:Rituximab therapy could induce remission of proteinuria and stabilization of renal function in non-responsive iMN patients, even those with damaged renal function. Anti-PLA2R antibodies may be used as a marker for individualized rituximab dosage and treatment monitoring.
Authors: Inês Duarte; João Oliveira; Cristina Outerelo; Iolanda Godinho; Marta Pereira; Paulo Fernandes; Sofia Jorge; Joana Gameiro Journal: J Bras Nefrol Date: 2022 Apr-Jun