A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab. A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab. Primary membranous nephropathy (PMN) is one of the most common causes of nephrotic syndrome in adults.1Couser W. Primary membranous nephropathy.Clin J Am Soc Nephrol. 2017; 12: 983-997Crossref PubMed Scopus (245) Google Scholar In 70%–80% of cases, the disease is mediated by autoantibodies targeting the phospholipase A2 receptor (PLA2R) expressed in podocytes and in 3%–5% by autoantibodies to thrombospondin type 1 domain–containing 7A (THSD7A).2Beck Jr., L.H. Bonegio R.G. Lambeau G. et al.M-Type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.N Engl J Med. 2009; 361: 11-21Crossref PubMed Scopus (1419) Google Scholar, 3Ronco P. Debiec H. Molecular pathogenesis of membranous nephropathy.Annu Rev Pathol. 2020; 15: 287-313Crossref PubMed Scopus (42) Google Scholar, 4Tomas N.M. Beck Jr., L.H. Meyer-Schwesinger C. et al.Thrombospondin type-1 domain–containing 7A in idiopathic membranous nephropathy.N Engl J Med. 2014; 371: 2277-2287Crossref PubMed Scopus (496) Google Scholar Spontaneous remission occurs in one-third of patients,5Polanco N. Gutiérrez E. Covarsí A. et al.Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy.J Am Soc Nephrol. 2010; 21: 697-704Crossref PubMed Scopus (248) Google Scholar and therefore an observational period of at least 6 months is recommended.6Waldman M. Austin H.A. Treatment of idiopathic membranous nephropathy.J Am Soc Nephrol. 2012; 23: 1617-1630Crossref PubMed Scopus (62) Google Scholar, 7Hofstra J.M. Fervenza F.C. Wetzels J.F.M. Treatment of idiopathic membranous nephropathy.Nat Rev Nephrol. 2013; 9: 443-458Crossref PubMed Scopus (88) Google Scholar, 8Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work GroupKDIGO clinical practice guidelines for glomerulonephritis.Kidney Int Suppl. 2012; 2 (139–27)Google Scholar Conversely, about 50% of cases with persistent nephrotic syndrome eventually progress to end-stage kidney disease, and immunosuppressive therapy is recommended for these patients. Controversy persists about the most effective type of immunosuppressive regimen. The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for glomerulonephritis recommended a 6-month cyclic regimen of alternating alkylating agents (usually cyclophosphamide) plus corticosteroids for patients at high risk of progression, since it was the only regimen that was shown to be effective in preventing end-stage kidney disease.8Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work GroupKDIGO clinical practice guidelines for glomerulonephritis.Kidney Int Suppl. 2012; 2 (139–27)Google Scholar, 9Ponticelli C. Zucchelli P. Passerini P. et al.A randomized trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy.N Engl J Med. 1989; 320: 8-13Crossref PubMed Scopus (240) Google Scholar, 10Ponticelli C. Zucchelli P. Passerini P. et al.A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy.Kidney Int. 1995; 48: 1600-1604Abstract Full Text PDF PubMed Scopus (336) Google Scholar, 11Ponticelli C. Altieri P. Scolari F. et al.A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.J Am Soc Nephrol. 1998; 9: 444-450Crossref PubMed Google Scholar, 12Jha V. Ganguli A. Saha T.K. et al.A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy.J Am Soc Nephrol. 2007; 18: 1899-1904Crossref PubMed Scopus (215) Google Scholar However, given the important number of serious adverse events associated with cumulative doses of alkylating agents, treatment alternatives were introduced. Calcineurin inhibitors (both cyclosporine and tacrolimus) have shown efficacy in inducing remission of nephrotic syndrome in about 70% of patients.13Cattran D.C. Appel G.B. Hebert L.A. et al.Cyclosporine in patients with steroid-resistant membranous nephropathy: a randomized trial.Kidney Int. 2001; 59: 1484-1490Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar,14Praga M. Barrio V. Juárez G.F. Luño J. Tacrolimus monotherapy in membranous nephropathy: a randomized controlled trial.Kidney Int. 2007; 71: 924-930Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar However, the main limitation of these drugs is the high rate of relapse after discontinuation. An observational study found a reduction in relapse rates when rituximab was administered at the time of tapering off cyclosporine or tacrolimus,15Segarra A. Praga M. Ramos N. et al.Successful treatment of membranous glomerulonephritis with rituximab in calcineurin inhibitor-dependent patients.Clin J Am Soc Nephrol. 2009; 4: 1083-1088Crossref PubMed Scopus (82) Google Scholar and a pilot study reported encouraging results of a combined therapy with cyclosporine plus rituximab in high-risk PMN patients.16Waldman M. Beck Jr., L.H. Braun M. et al.Membranous nephropathy: pilot study of a novel regimen cyclosporine and Int Full Text Full Text PDF PubMed Scopus Google Scholar the efficacy of rituximab monotherapy P. P. A. et in idiopathic membranous nephropathy.J Am Soc Nephrol. 2012; 23: PubMed Scopus Google Scholar A of rituximab was to be effective for of remission in an observational P. P. G. rituximab to to therapy in idiopathic membranous nephropathy.Clin J Am Soc Nephrol. 2007; PubMed Scopus Google Scholar in clinical higher doses were for Debiec H. E. et for membranous nephropathy: a 6-month trial with Am Soc Nephrol. 2017; PubMed Scopus Google Scholar, F.C. Appel G.B. et or cyclosporine in the treatment of membranous nephropathy.N Engl J Med. PubMed Scopus Google Scholar, Debiec H. et rituximab and remission in membranous nephropathy.Clin J Am Soc Nephrol. PubMed Scopus Google Scholar the superior efficacy of rituximab versus cyclosporine in the of study was achieved a of F.C. Appel G.B. et or cyclosporine in the treatment of membranous nephropathy.N Engl J Med. PubMed Scopus Google Scholar The for comparing the 6-month cyclic alternating treatment with corticosteroids and cyclophosphamide with the alternatives was in a J. D.C. et and treatment of a Kidney Disease: Improving Global Outcomes (KDIGO) Int. Full Text Full Text PDF PubMed Scopus Google Scholar We the Treatment with Tacrolimus and and in study to cyclic alternating treatment of corticosteroids and cyclophosphamide with a sequential treatment of tacrolimus and rituximab in the and of nephrotic syndrome remission for 24 months. In the of after remission and the of anti-PLA2R autoantibodies the of the patients were for of were the for were the to in the study and of a of membranous nephropathy The 86 patients who the were assigned to the corticosteroid-cyclophosphamide group or to the tacrolimus-rituximab group in significant groups were at were in and anti-PLA2R was in showed at and patients patients with or anti-PLA2R at and patient was Kidney were months patients PMN and PMN to treatment patients was to the Kidney as of of 6 of 43 patients anti-PLA2R was at of 11 of 43 patients anti-PLA2R was at treatment of of 43 of 43 of of 43 of 43 A2 receptor receptor as or was to the Kidney Anti-PLA2R as In 6 of 43 patients anti-PLA2R was at In 11 of 43 patients anti-PLA2R was at in a A2 receptor receptor as or patients at least 1 month of the assigned patients in the corticosteroid-cyclophosphamide group and 6 in the tacrolimus-rituximab group the The in the corticosteroid-cyclophosphamide group and in the tacrolimus-rituximab the complete assigned to the corticosteroid-cyclophosphamide group a of methylprednisolone of in months and with a cumulative of The cumulative of methylprednisolone was The cumulative of cyclophosphamide was and of tacrolimus in the tacrolimus-rituximab group in patients in group a of rituximab in 2 1 in 1 at months and and 2 doses of tacrolimus month the follow-up period after the of the assigned patients in each group were to a to a of efficacy of the assigned In the corticosteroid-cyclophosphamide group, 2 patients were with rituximab at month 2 patients tacrolimus month and 1 patient cyclosporine month In the tacrolimus-rituximab group, the patients a 6-month cyclic treatment with corticosteroid and cyclophosphamide at month month or month the patients who were to a were to be was complete in of the 86 patients. patients (83.7%) in the corticosteroid-cyclophosphamide group and 25 patients (58.1%) in the tacrolimus-rituximab group a primary outcome of remission at 24 months (relative risk 95% confidence interval 1.08 to The significant in the primary outcome of in the corticosteroid-cyclophosphamide group and of in the tacrolimus-rituximab group 95% to The in the number of patients with complete or partial remission in both groups was significant at month and was the study outcome of complete or partial remission at to 24 cyclophosphamide risk of 43 of 43 of 43 of 43 of 43 of 43 of 43 of 43 of 43 of 43 cyclophosphamide risk of of of of of of of of of of confidence the patients who the the patients who the of trial In both the primary outcome was the composite of complete or partial remission at 24 or 95% in a confidence The the patients who the the patients who the of trial In both the primary outcome was the composite of complete or partial remission at 24 months. or 95% shown in and 26 patients (60%) in the corticosteroid-cyclophosphamide group achieved complete remission at 24 months. In the tacrolimus-rituximab group, 11 patients (26%) achieved complete remission at 24 months 95% 1.34 to remission at to 24 cyclophosphamide risk of 43 of 43 of 43 of 43 of 43 of 43 of 43 of 43 of 43 of 43 cyclophosphamide risk of of of of of of of of of of confidence the patients who the the patients who the of trial In both the primary outcome was the composite of complete or partial remission at 24 or 95% in a confidence The the patients who the the patients who the of trial In both the primary outcome was the composite of complete or partial remission at 24 months. or 95% A for a greater efficacy of the corticosteroid-cyclophosphamide treatment was found by of anti-PLA2R and were found in patients of patients were compared who achieved remission and with a significantly higher proportion of and a significantly higher were a at to at 24 months in the corticosteroid-cyclophosphamide group and at to 1 at 24 months in the tacrolimus-rituximab group a at to at 24 months in the corticosteroid-cyclophosphamide group and at to at 24 months in the tacrolimus-rituximab group was a for higher of rate in the corticosteroid-cyclophosphamide group than in the tacrolimus-rituximab group the follow-up 24 the of patients with a of were 1 in the corticosteroid-cyclophosphamide group and in the tacrolimus-rituximab group The of patients with at 24 months were in the corticosteroid-cyclophosphamide group and in the tacrolimus-rituximab group The only patient who end-stage kidney disease was a who assigned to the corticosteroid-cyclophosphamide group. months after treatment was the study of persistent and and to rituximab doses of 1 response was and was months after Anti-PLA2R showed a significant decrease in both groups The of patients who achieved response at and 6 months were significantly higher in the corticosteroid-cyclophosphamide group (77% and 92%, than in the tacrolimus-rituximab group (45% and 70%, patients who achieved response the study remission of nephrotic syndrome at 24 months. response at months and 6 months was associated with remission at 24 months. patients showed a in anti-PLA2R and a significantly proportion of compared with patients who achieved a complete or partial remission of nephrotic syndrome of anti-PLA2R and of response to treatment phospholipase A2 of were compared with the in a phospholipase A2 of were compared with the of the 36 patients in the corticosteroid-cyclophosphamide group, and of the 25 patients in the tacrolimus-rituximab group who achieved partial remission a relapse The in the tacrolimus-rituximab group occurred at month months after tacrolimus discontinuation. of occurred in patients who an response at month 6 and were by a of anti-PLA2R The relapse occurred in a patient in anti-PLA2R at Tacrolimus was in 2 patients and the one was with The relapse in the corticosteroid-cyclophosphamide group occurred at month in an patient who response at month In the relapse was by a of anti-PLA2R and the patient was with patients 6 the corticosteroid-cyclophosphamide group and the tacrolimus-rituximab at least 1 adverse adverse events were of or but were were adverse events and adverse events patient in the corticosteroid-cyclophosphamide group than in the tacrolimus-rituximab group patients in the corticosteroid-cyclophosphamide group and kidney and were common in the tacrolimus-rituximab group. was a significant the of and the of both in the trial and in each treatment group for the group and for the cyclophosphamide group, for the adverse events occurred the months of the trial of but only of the serious adverse events occurred events to treatment for the in number of events adverse adverse adverse events in at least of patients or serious adverse and kidney for patients as for events as for the in number of events groups. in a for patients as for events as were significant in the of serious adverse events groups. The only of serious kidney occurred in the tacrolimus-rituximab group, of the serious occurred in the corticosteroid-cyclophosphamide group. cases of were of was to be to the treatment occurred in the corticosteroid-cyclophosphamide group and at and 11 and 1 in the tacrolimus-rituximab group at 1 Anti-PLA2R was at in the patients with the time of the 2 patients in the corticosteroid-cyclophosphamide group were in clinical The study to the that sequential therapy with tacrolimus and rituximab was superior to cyclic alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in patients with In found that treatment with corticosteroid and cyclophosphamide was effective than sequential treatment with tacrolimus and rituximab in inducing The of was in the corticosteroid-cyclophosphamide group, with a significant in the number of at months. most were complete in the corticosteroid-cyclophosphamide group, most were partial in the tacrolimus-rituximab group. with calcineurin inhibitors and rituximab have that these drugs effective at inducing remission in that the of calcineurin inhibitors in PMN be to in a C. M. et of kidney podocytes is a target of the of cyclosporine Med. PubMed Scopus Google Scholar However, found that tacrolimus induced a decrease in anti-PLA2R in with A. V. et follow-up study of membranous nephropathy with tacrolimus and corticosteroids versus cyclical corticosteroids and Int 2017; Full Text Full Text PDF PubMed Scopus Google Scholar The main limitation of calcineurin inhibitors is the high relapse rate after in of patients. In the F.C. Appel G.B. et or cyclosporine in the treatment of membranous nephropathy.N Engl J Med. PubMed Scopus Google Scholar rituximab at 1 and after and 2 at month 6 the patient complete was compared with cyclosporine given for months. were significant in the number of at months. However, a higher proportion of patients in the cyclosporine group after treatment and the number of patients in remission at 24 months was significantly higher in the rituximab group In the number of at 6 months was in the tacrolimus-rituximab group than in the corticosteroid-cyclophosphamide group. at month 6 the in remission the number of complete after rituximab An important was the number of after tacrolimus discontinuation. This with a observational study that reported a of at the of calcineurin to in PMN patients who to cyclosporine or A. Praga M. Ramos N. et al.Successful treatment of membranous glomerulonephritis with rituximab in calcineurin inhibitor-dependent patients.Clin J Am Soc Nephrol. 2009; 4: 1083-1088Crossref PubMed Scopus (82) Google Scholar The pathogenesis of after tacrolimus in PMN and the rituximab rituximab is effective in the number of nephrotic syndrome in kidney as disease and and M. et for nephrotic syndrome or nephrotic a 2014; Full Text Full Text PDF PubMed Scopus Google P. P. et in or idiopathic nephrotic Am Soc Nephrol. 2014; PubMed Scopus Google Scholar In the the number of for the than number of at 24 months. the response rate of in the tacrolimus-rituximab group was similar to that with in Debiec H. E. et for membranous nephropathy: a 6-month trial with Am Soc Nephrol. 2017; PubMed Scopus Google F.C. Appel G.B. et or cyclosporine in the treatment of membranous nephropathy.N Engl J Med. PubMed Scopus Google Scholar and than that after cyclosporine or tacrolimus the of rituximab D.C. Appel G.B. Hebert L.A. et al.Cyclosporine in patients with steroid-resistant membranous nephropathy: a randomized trial.Kidney Int. 2001; 59: 1484-1490Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar,14Praga M. Barrio V. Juárez G.F. Luño J. Tacrolimus monotherapy in membranous nephropathy: a randomized controlled trial.Kidney Int. 2007; 71: 924-930Abstract Full Text Full Text PDF PubMed Scopus (216) Google A. V. et follow-up study of membranous nephropathy with tacrolimus and corticosteroids versus cyclical corticosteroids and Int 2017; Full Text Full Text PDF PubMed Scopus Google Scholar the it be that the tacrolimus-rituximab group in the corticosteroid-cyclophosphamide and were higher anti-PLA2R a higher of and a of in group. these at have the an outcome in the tacrolimus-rituximab group. the of anti-PLA2R autoantibodies as a of the disease in 70%–80% of patients with a cumulative number of have the of of anti-PLA2R to clinical to the and to the of immunosuppressive Jr., L.H. Bonegio R.G. Lambeau G. et al.M-Type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.N Engl J Med. 2009; 361: 11-21Crossref PubMed Scopus (1419) Google M. Wetzels P. The anti-PLA2R in membranous nephropathy: and a after Int. Full Text Full Text PDF PubMed Scopus Google Scholar, Fervenza F.C. A for a to membranous nephropathy.J Am Soc Nephrol. 2017; PubMed Scopus Google Scholar, E. G. A2 receptor autoantibodies and clinical outcome in patients with primary membranous nephropathy.J Am Soc Nephrol. 2014; PubMed Scopus Google Scholar, P. Debiec H. et receptor outcome of membranous nephropathy.J Am Soc Nephrol. PubMed Scopus Google Scholar, A2 receptor and treatment of membranous nephropathy: a J Am Soc Nephrol. 2014; 9: PubMed Scopus Google Scholar We found that both corticosteroid-cyclophosphamide and tacrolimus-rituximab induced a significant reduction in anti-PLA2R response occurred in the corticosteroid-cyclophosphamide group. and in a reduction in than drugs as rituximab or calcineurin and have the of alkylating agents in the most cases of A. et remission in membranous nephropathy: cyclophosphamide versus Int. Full Text Full Text PDF PubMed Scopus Google Scholar, et for membranous nephropathy: a controlled 2013; Full Text Full Text PDF PubMed Scopus Google Scholar, C. and in mediated kidney Rev Nephrol. 15: PubMed Scopus Google Scholar response was by clinical remission in the of the of anti-PLA2R for a treatment of the The rate of adverse was significantly higher patients with were in the number of serious adverse have shown that in PMN by serious J.M. Wetzels risk after cyclophosphamide treatment in idiopathic membranous nephropathy.Clin J Am Soc Nephrol. 2014; 9: PubMed Scopus Google P. A. et of rituximab compared with steroids and cyclophosphamide for idiopathic membranous nephropathy.J Am Soc Nephrol. 2017; PubMed Scopus Google Scholar However, cumulative doses of cyclophosphamide were higher than in have that of doses of the results in M. H. et of idiopathic membranous nephropathy in patients with cyclophosphamide and 2009; PubMed Scopus Google Scholar Anti-PLA2R to treatment in patients in a response is have reported encouraging results with the of of cyclophosphamide as a for cyclophosphamide in patients with the alternating cyclic regimen of corticosteroids and V. A. G. cyclophosphamide and is a and effective treatment for idiopathic membranous nephropathy.Clin Kidney J. 2017; PubMed Scopus Google P. cyclophosphamide and steroids immunological and clinical remission in and primary membranous 23: PubMed Scopus Google Scholar the it be important to the of doses of corticosteroids the of the of treatment with corticosteroids and cyclophosphamide be compared with calcineurin inhibitors and treatment with tacrolimus 6 months or higher and doses of rituximab the remission rates in patients with tacrolimus-rituximab be in The study important was of and outcome The by or of anti-PLA2R and anti-PLA2R were in a number of patients. were about the of rituximab was However, study was a controlled trial that compared the cyclic alternating treatment with corticosteroids and cyclophosphamide versus the alternatives treatment with tacrolimus and with a and follow-up period that to important about the treatment of PMN in clinical In treatment with corticosteroid-cyclophosphamide induced remission of nephrotic syndrome in a significantly greater number of patients than treatment with were in the group. This randomized, controlled trial with a was by the and at in 1 in the A complete of study and is in the of the and study for the trial in the The study was J. G. A. et al.A and open-label controlled randomized trial to the efficacy of sequential treatment with tacrolimus-rituximab versus steroids plus cyclophosphamide in patients with primary membranous nephropathy: the Kidney J. PubMed Scopus Google Scholar A and the of the and the of the the trial at The trial is at patients with PMN were patients were for an observational period of at least 6 months. were a decrease of the observational and the observational patients the of with receptor for at least 2 months and controlled for at least with in of or the In the of a was were causes of membranous nephropathy or disease, treatment with another or or to drugs treatment with corticosteroids months immunosuppressive months or to or with a risk for the patient and or Full as as and in We a in for with an to with corticosteroid-cyclophosphamide or tacrolimus-rituximab. The were assigned as each the In the corticosteroid-cyclophosphamide group, patients methylprednisolone at months and at and to months and patients cyclophosphamide for and for In the tacrolimus-rituximab group, patients tacrolimus to target of for 6 months. patients rituximab and tacrolimus was by with complete at the of month Tacrolimus was in of kidney with patients 1 and groups with a the treatment were to in of of and patients with a relapse of nephrotic syndrome were as The primary outcome was complete or partial remission at 24 months. the rate of complete and partial remission at and 24 relapse of nephrotic syndrome at and 24 response at to 24 and the of patients of of and with kidney at 24 and adverse were the proportion of patients with adverse events the study and cumulative of each study Complete remission was as a reduction of to a plus kidney partial remission as a reduction of and a plus response was as a reduction of Relapses were as a of and at least the in or in patients with partial or complete were to be for anti-PLA2R when were as with a C. C. et of a for the of autoantibodies phospholipase A2 receptor in primary membranous nephropathy.Clin 2013; PubMed Scopus Google Scholar response was by a of anti-PLA2R was with the Kidney the results of hypothesized a remission rate of at 2 for the corticosteroid-cyclophosphamide group and for the tacrolimus-rituximab group. We to a of Primary outcome remission at 24 was by and the with 95% and compared with or for complete or partial remission at and months were for the of of the primary outcome were to the to of and and were with the of with the 2 groups in were with or as were with or as as and months and 24 were with the of The and as and as with and anti-PLA2R were as and to time to nephrotic syndrome were with the of and patients who of the study the primary outcome were the a was as an of the time and the in The was as when the of the of the time was associated with were with the of a The of was reported as the with 95% A of the is in were by for treatment groups and and Work in study was by the and and and in of the of the for the of a for in with for of and and and We the trial at and the patients who in the and the and in the and to the of the the of the and the F. A A and and and the the be groups with an the for with The calcineurin therapy in membranous trial that in primary membranous nephropathy treatment with tacrolimus plus rituximab be superior to a regimen of alternating cyclophosphamide and This was the were achieved in and of these were complete these results with of the compared rituximab with cyclosporine in an the of calcineurin for PDF progress in membranous Treatment with Tacrolimus and and in PMN the of a corticosteroid-cyclophosphamide regimen However, of these to the In patients nephrotic syndrome with rate a at risk of disease progression. PDF The and for We about the of a treatment of membranous but that the Treatment with Tacrolimus and and in PMN for results the efficacy of cyclic alternating treatment with corticosteroids and cyclophosphamide of at 24 most of the 6-month alternating is by in inducing and clinical remission (77% and at months) be the of and of corticosteroids and PDF phospholipase A2 receptor rituximab treatment in membranous the Treatment with Tacrolimus and versus and in Primary et have shown that a sequential is effective to the to membranous events were in the have shown that and higher immunological remission rate than rituximab and that rituximab is and to PDF The et for and for the results in of patients with membranous nephropathy with an A2 rituximab We that the of A2 receptor a and treatment of membranous PDF