Rituximab in Idiopathic Membranous Nephropathy

被引:253
作者
Ruggenenti, Piero [1 ,2 ]
Cravedi, Paolo [1 ]
Chianca, Antonietta [1 ]
Perna, Annalisa [1 ]
Ruggiero, Barbara [1 ]
Gaspari, Flavio [1 ]
Rambaldi, Alessandro [3 ]
Marasa, Maddalena [1 ]
Remuzzi, Giuseppe [1 ,2 ]
机构
[1] Clin Res Ctr Rare Dis, Mario Negri Inst Pharmacol Res, Ranica, Italy
[2] Osped Riuniti Bergamo, Azienda Osped, Nephrol Unit, Bergamo, Italy
[3] Osped Riuniti Bergamo, Azienda Osped, Hematol Unit, Bergamo, Italy
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2012年 / 23卷 / 08期
关键词
METHYLPREDNISOLONE PLUS CHLORAMBUCIL; NEPHROTIC SYNDROME; ANTI-PLA(2)R AUTOANTIBODIES; CONTROLLED-TRIAL; THERAPY; CYCLOPHOSPHAMIDE; GRANULOMATOSIS; MECHANISMS; REMISSION;
D O I
10.1681/ASN.2012020181
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Selective depletion of B cells with the mAb rituximab may benefit the autoimmune glomerular disease idiopathic membranous nephropathy (IMN). Here, we describe our experience treating 100 consecutive IMN patients with persistent nephrotic syndrome with rituximab. We defined complete remission as persistent proteinuria <0.3 g/24 h and partial remission as persistent proteinuria <3 g/24 h, each also having >50% reduction in proteinuria from baseline. During a median follow-up of 29 months after rituximab administration, 65 patients achieved complete or partial remission. The median time to remission was 7.1 months. All 24 patients who had at least 4 years of follow-up achieved complete or partial remission. Rates of remission were similar between patients with or without previous immunosuppressive treatment. Four patients died and four progressed to ESRD. Measured GFR increased by a mean 13.2 (SD 19.6) ml/min per 1.73 m(2) among those who achieved complete remission. Serum albumin significantly increased and albumin fractional clearance decreased among those achieving complete or partial remission. Proteinuria at baseline and the follow-up duration each independently predicted the decline of proteinuria. Furthermore, the magnitude of proteinuria reduction significantly correlated with slower GFR decline (P=0.0001). No treatment-related serious adverse events occurred. In summary, rituximab achieved disease remission and stabilized or improved renal function in a large cohort of high-risk patients with IMN.
引用
收藏
页码:1416 / 1425
页数:10
相关论文
共 46 条
[1]   MEMBRANOUS NEPHROPATHY [J].
AUSTIN, HA ;
ANTONOVYCH, TT ;
MACKAY, K ;
BOUMPAS, DT ;
BALOW, JE .
ANNALS OF INTERNAL MEDICINE, 1992, 116 (08) :672-682
[2]   Rituximab-Induced Depletion of Anti-PLA2R Autoantibodies Predicts Response in Membranous Nephropathy [J].
Beck, Laurence H., Jr. ;
Fervenza, Fernando C. ;
Beck, David M. ;
Bonegio, Ramon G. B. ;
Malik, Fahim A. ;
Erickson, Stephen B. ;
Cosio, Fernando G. ;
Cattran, Daniel C. ;
Salant, David J. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2011, 22 (08) :1543-1550
[3]   M-Type Phospholipase A(sub 2) Receptor as Target Antigen in Idiopathic Membranous Nephropathy. [J].
Beck, Laurence H., Jr. ;
Bonegio, Ramon G. B. ;
Lambeau, Gerard ;
Beck, David M. ;
Powell, David W. ;
Cummins, Timothy D. ;
Klein, Jon B. ;
Salant, David J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (01) :11-21
[4]   Rituximab Therapy for Membranous Nephropathy: A Systematic Review [J].
Bomback, Andrew S. ;
Derebail, Vimal K. ;
McGregor, Julie G. ;
Kshirsagar, Abhijit V. ;
Falk, Ronald J. ;
Nachman, Patrick H. .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2009, 4 (04) :734-744
[5]   Have We Changed the Outcome in Membranous Nephropathy? A Propensity Study on the Role of Immunosuppressive Therapy [J].
Cattran, Daniel C. ;
Reich, Heather N. ;
Kim, S. Joseph ;
Troyanov, Stephan .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2011, 6 (07) :1591-1598
[6]   Cyclosporine in patients with steroid-resistant membranous nephropathy: A randomized trial [J].
Cattran, DC ;
Appel, GB ;
Hebert, LA ;
Hunsicker, LG ;
Pohl, MA ;
Hoy, WE ;
Maxwell, DR ;
Kunis, CL .
KIDNEY INTERNATIONAL, 2001, 59 (04) :1484-1490
[7]   Titrating rituximab to circulating B cells to optimize lymphocytolytic therapy in idiopathic membranous nephropathy [J].
Cravedi, Paolo ;
Ruggenenti, Piero ;
Sghirlanzoni, Maria Chiara ;
Remuzzi, Giuseppe .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 2 (05) :932-937
[8]   Circulating Anti-PLA2R Autoantibodies to Monitor Immunological Activity in Membranous Nephropathy [J].
Cravedi, Paolo ;
Ruggenenti, Piero ;
Remuzzi, Giuseppe .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2011, 22 (08) :1400-1402
[9]   Brief report - Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies [J].
Debiec, H ;
Guigonis, V ;
Mougenot, B ;
Decobert, F ;
Haymann, J ;
Bensman, A ;
Deschenes, G ;
Ronco, PM .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (26) :2053-2060
[10]  
Faurschou M, 2008, J RHEUMATOL, V35, P100