Rituximab in idiopathic membranous nephropathy: a one-year prospective study.

Currently available monoclonal antibodies against the B cell surface antigen CD20 have been employed to explore whether specific inhibition of B cells may help improve the outcome of idiopathic membranous nephropathy (IMN) and may avoid the side effects of steroids and immunosuppressants. This prospective, observational study evaluated the 1-yr outcome of eight IMN patients with persistent (>6 mo) urinary protein excretion > 3.5 g/24 h given four weekly infusions of the anti-CD20 antibody rituximab (375 mg/m(2)). At 3 and 12 mo, proteinuria significantly decreased from mean (+/- SD) 8.6 +/- 4.2 to 4.3 +/- 3.3 (-51%, P < 0.005) and 3.0 +/- 2.5 (-66%, P < 0.005) g/24 h, albumin fractional clearance from 2.3 +/- 2.1 to 1.2 +/- 1.7 (-47%, P < 0.05) and 0.5 +/- 0.6 (-76%, P < 0.003), and serum albumin concentration increased from 2.7 +/- 0.5 to 3.1 +/- 0.3 (+21%, P < 0.05) and 3.5 +/- 0.4 (+41%, P < 0.05) mg/dl. At 12 mo, proteinuria decreased to < or =0.5 g/24 h or < or =3.5 g/24 h in two and three patients, respectively. Proteinuria decreased in the remaining patients by 74%, 44%, and 41%, respectively. Body weight, diastolic BP, and serum cholesterol progressively decreased in parallel with an improvement of edema in all patients. Renal function stabilized (Delta1/creatinine: +0.002 +/- 0.007). CD20 B lymphocytes fell below normal ranges up to study-end. No patient had major drug-related events or major changes in other laboratory parameters. Rituximab thus promotes sustained disease remission in patients otherwise predicted to progress to ESRD, and it is safe. The long-term risk/benefit profile of this novel, disease-specific approach seems much more favorable to that of commonly employed immunosuppressive drugs.

[1]  W. Wilson,et al.  Rituximab treatment of refractory fludarabine-associated immune thrombocytopenia in chronic lymphocytic leukemia. , 2002, Blood.

[2]  R. Fanin,et al.  Efficacy of selective B cell blockade in the treatment of rheumatoid arthritis: evidence for a pathogenetic role of B cells. , 2002, Arthritis and rheumatism.

[3]  U. Germing,et al.  Treatment of relapsed idiopathic thrombocytopenic purpura with the anti‐CD20 monoclonal antibody rituximab: a pilot study , 2002, European journal of haematology.

[4]  J. Haymann,et al.  Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies. , 2002, The New England journal of medicine.

[5]  P. Kincaid‐smith Pharmacological management of membranous nephropathy , 2002, Current opinion in nephrology and hypertension.

[6]  M. Hogan,et al.  Response of Wegener's granulomatosis to anti-CD20 chimeric monoclonal antibody therapy. , 2001, Arthritis and rheumatism.

[7]  P. Johnson,et al.  Rituximab: mechanisms and applications , 2001, British Journal of Cancer.

[8]  E. Løkkevik,et al.  Favourable response to therapy with the anti‐CD20 monoclonal antibody rituximab in primary chronic cold agglutinin disease , 2001, British journal of haematology.

[9]  R. Fanin,et al.  Rituximab in a case of cold agglutinin disease , 2001, British journal of haematology.

[10]  C. Schmid,et al.  Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease. , 2001, Kidney international.

[11]  D. Huhn,et al.  Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. , 2001, Blood.

[12]  H. Hasselbalch,et al.  Sustained remission of platelet counts following monoclonal anti‐CD20 antibody therapy in two cases of idiopathic autoimmune thrombocytopenia
and neutropenia , 2001, European journal of haematology.

[13]  G. Remuzzi,et al.  Progression, remission, regression of chronic renal diseases , 2001, The Lancet.

[14]  J. Edwards,et al.  Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes. , 2001, Rheumatology.

[15]  M. Czuczman,et al.  Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin's lymphoma: safety and efficacy of re-treatment. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  S. Piscitelli,et al.  A pilot study of low-dose fludarabine in membranous nephropathy refractory to therapy. , 1999, Clinical nephrology.

[17]  G. Remuzzi,et al.  In chronic nephropathies prolonged ACE inhibition can induce remission: dynamics of time-dependent changes in GFR. Investigators of the GISEN Group. Gruppo Italiano Studi Epidemiologici in Nefrologia. , 1999, Journal of the American Society of Nephrology : JASN.

[18]  A. Pestronk,et al.  IgM antibody-related polyneuropathies: B-cell depletion chemotherapy using Rituximab , 1999, Neurology.

[19]  B. Hall,et al.  Mycophenolate mofetil prevents the induction of active Heymann nephritis: association with Th2 cytokine inhibition. , 1998, Journal of the American Society of Nephrology : JASN.

[20]  G. Remuzzi,et al.  Recent developments in the management of membranous nephropathy. , 1997, Expert opinion on investigational drugs.

[21]  A. Komatsuda,et al.  IgG subclasses in patients with membranoproliferative glomerulonephritis, membranous nephropathy, and lupus nephritis. , 1997, Kidney international.

[22]  I. Stamenkovic,et al.  Inhibition of the CD40-CD40ligand pathway prevents murine membranous glomerulonephritis. , 1995, Kidney international.

[23]  D. de Zeeuw,et al.  Short-term antiproteinuric response to antihypertensive treatment predicts long-term GFR decline in patients with non-diabetic renal disease. , 1994, Kidney international. Supplement.

[24]  H. Parving,et al.  Reduction in albuminuria predicts diminished progression in diabetic nephropathy. , 1994, Kidney international. Supplement.

[25]  R. Monteiro,et al.  Glomerular and serum immunoglobulin G subclasses in membranous nephropathy and anti-glomerular basement membrane nephritis. , 1988, Clinical immunology and immunopathology.

[26]  E. Pettersson,et al.  The evolution of membranous glomerulonephritis reconsidered: new insights from a study on relapsing disease. , 1987, Clinical nephrology.

[27]  H. Rosenberg,et al.  Primary glomerular diseases (primary glomerulopathies). , 1986, Pathology, research and practice.

[28]  A. Woodroffe,et al.  Glomerular IgG subclass distribution in human glomerulonephritis. , 1983, Clinical nephrology.

[29]  D. Kerjaschki,et al.  Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats , 1983, The Journal of experimental medicine.

[30]  F. Velásquez Forero,et al.  [Idiopathic membranous glomerulonephritis]. , 1979, Boletin medico del Hospital Infantil de Mexico.