Abstract: Objective:To  investigate  to  the  efficacy  and  safety  of  obinutuzumab  in  the  treatment  of  high  risk  or refractory phospholipase A2 receptor associated membranous nephropathy.    Methodology:Patients with biopsy-proven MN or serum anti-phospholipase A2 receptor antibody （aPLA2Rab） titers≥14 RU/ml treated with obinutuzumab （1 g× 2） in the National Clinical  Medical  Research  Center  for  Renal  Diseases  at  Jinling  Hospital  from  September  2022  to  December 2023 were  retrospectively  analyzed.  High  risk  was  classified  according  to  kidney  disease:  Improving  Global  Outcomes guideline and expert recommendation. Refractory disease was termed as patients received immunosuppressive agents such as cyclophosphamide，  calcineurin  inhibitors  or  Rituximab  with  or  without  steroids  for  more  than  6  months  but  have  not  yet achieved remission  （proteinuria  decline < 50%  and > 3.5  g/24h）.      Results: Our  analysis  included  72  patients  （56 refractory， 16 high risk MN）， baseline proteinuria was 10.2 g/24h. 70 （97%） patients achieved remission at month 12， including 24 （33%） achieved complete remission （CR）. The median time to remission was 3 （3 ~ 6） months.  Remission  

rate， CR rate of high risk and refractory MN was 100% and 96%， 56% and 27% respectively. CR rate was significantly high in high-risk group than refractory group （HR = 2.497，95%CI 1.041~ 5.989）. Obinutuzumab significantly reduced 24- hour proteinuria  and  increased  serum  albumin，  estimated  glomerular  filtration  rate  since  week  6.  Complete  depletion  of circulating B cell was maintained in all patients within 3 months and the median time to B cell reconstitution （CD20+ cells

Key words: membranous nephropathy, Obinutuzumab, phospholipase A2 receptor, high risk , refractory