Rituximab in patients with membranous nephropathy and kidney insufficiency

Abstract

Introduction: Patients with membranous nephropathy and kidney insufficiency have an extremely high risk of progression to end-stage renal disease. Whether rituximab can effectively treat membranous nephropathy patients with renal dysfunction remains unknown at present. The aim of our study was to evaluate the effectiveness and safety of rituximab (RTX) in membranous nephropathy with kidney insufficiency.Methods: We retrospectively analyzed the clinical data of 35 membranous nephropathy patients with kidney insufficiency administered in the First Affiliated Hospital of Zhengzhou University between January 2020 and December 2021. Patients were followed every 1–3 months for a total of 6 months. Clinical data were collected including anti-phospholipase A2 receptor antibody (anti-PLA2R antibody) quantification, 24-h urinary protein, serum albumin, and serum creatinine. The percentage of patients who achieved clinical remission was measured.Results: There were 7 (20%) patients who achieved complete or partial response at 6 months after RTX treatment. After 6 months of treatment, patients were clinically improved as evidenced by significant improvements in anti- PLA2R antibody titer [7.70 (5.72, 16.72) vs. 59.20 (17.70, 187.50) RU/ml, p < 0.001], 24-h urine protein [7.04 (4.43, 8.90) vs. 10.15 (4.83, 13.57) g/d, p < 0.001], serum albumin [30.55 (24.97, 33.27) vs. 21.40 (16.75, 25.00)g/L, p < 0.001], serum creatinine [99.50 (75.25, 140.25) vs. 152.00 (134.50, 232.50) µmol/L, p = 0.022], and estimated glomerular filtration rate (eGFR) [78.29 (50.15, 101.55) vs. 41.12 (26.53, 51.41) ml/min/1.73 m2, p = 0.045]. There were no significantly differences between responders and nonresponders in the baseline levels of anti-PLA2R antibodies, proteinuria, serum albumin, and renal function. After the RTX treatment, anti-PLA2R antibodies turned negative in all responders, but the antibody level persisted maintained positive in all but 5 nonresponders. The patients who achieved response maintained a stable kidney function during the study period, with eGFR 29.03 (28.76, 35.07) ml/min/1.73 m2 before rituximab treatment and 62.73 (62.34, 63.13) ml/min/1.73 m2 at the end of follow-up (p = 0.053).Conclusion: RTX therapy might be an alternative treatment in reducing proteinuria and maintaining stable renal function among membranous nephropathy patients even with kidney insufficiency.

Rituximab treatment for refractory nephrotic syndrome in adults: a multicenter retrospective study

“…Low eGFR especially below 60 mL/min/1.73 m 2 is a known predictor [ 24 ], indicating that RTX is not expected to be as effective, especially in MN. In addition, eGFR level may have an impact on the pharmacokinetics and tolerability of RTX [ 25 ]. For MN patients with kidney insufficiency, it is still controversial whether RTX can effectively reduce proteinuria, preserve kidney function, and delay or even reverse the progression of renal failure [ 6 , 26 , 27 ].…”

Primary Membranous Nephropathy - what do we know today?

“…Rituximab is a human/murine chimeric monoclonal antibody that targets CD20 molecule on the surface of pre-B cells as well as mature B lymphocytes. It induces the apoptosis of B-cells and reduces the production of autoantibodies including anti-PLA2R antibody [46]. The treatment of PMN with rituximab includes providing the patient with 1.0 g of rituximab twice within 2 weeks together with 375 mg/m 2 of rituximab given 1-4 times at weekly intervals [34].…”