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Clinical Nephrology
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Rituximab for Idiopathic Membranous Nephropathy: Who Can Benefit?

Piero Ruggenenti, Carlos Chiurchiu, Mauro Abbate, Annalisa Perna, Paolo Cravedi, Mario Bontempelli and Giuseppe Remuzzi
CJASN July 2006, 1 (4) 738-748; DOI: https://doi.org/10.2215/CJN.01080905
Piero Ruggenenti
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Carlos Chiurchiu
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Mauro Abbate
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Annalisa Perna
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Paolo Cravedi
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Mario Bontempelli
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Giuseppe Remuzzi
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Abstract

Rituximab effectively reduces proteinuria in patients with idiopathic membranous nephropathy (IMN), but response to treatment may vary from patient to patient. The association between baseline clinical, laboratory, and histology covariates and proteinuria reduction was evaluated retrospectively by multiple linear regression analysis at 3 mo after rituximab therapy in 14 patients with IMN with proteinuria >3.5 g/24 h while on angiotensin-converting enzyme inhibition for at least 6 mo and no previous remissions. The association strength was expressed by standardized β coefficients (SβC). Glomerular (SβC = 0.48, P = 0.049) and tubulointerstitial (TI) scores (SβC = 0.61, P = 0.003) predicted the outcome. Among glomerular and TI score components, tubular atrophy (SβC = 0.59, P = 0.003) and interstitial fibrosis (SβC = 0.60, P = 0.001) were significantly associated with 3-mo proteinuria. Urinary protein excretion decreased from 9.1 ± 4.0 to 4.6 ± 3.5 g/24 h (P < 0.001) in eight patients with TI score <1.7 but did not change in six with a score ≥1.7. Nine additional patients with IMN then were allocated prospectively to rituximab treatment on the basis of a TI score <1.7. Three-month proteinuria decreased in all patients from 8.9 ± 5.3 to 4.9 ± 3.9 g/24 h (P < 0.001) and serum albumin increased from 2.2 ± 0.6 to 2.8 ± 0.5 mg/dl (P < 0.01). Changes in serum albumin and cholesterol were inversely correlated (P < 0.02, r = −0.44). Rituximab achieved CD20 and CD19 depletion in all patients. In patients with IMN and nephrotic proteinuria despite angiotensin-converting enzyme inhibition therapy, renal biopsy findings may help in predicting response to rituximab and defining selection criteria for randomized trials that aim to assess the risk/benefit profile of B cell target therapy as compared with aspecific immunosuppressants and/or conservative therapy alone.

  • Received September 21, 2005.
  • Accepted April 12, 2006.
  • Copyright © 2006 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology
Vol. 1, Issue 4
July 2006
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Rituximab for Idiopathic Membranous Nephropathy: Who Can Benefit?
Piero Ruggenenti, Carlos Chiurchiu, Mauro Abbate, Annalisa Perna, Paolo Cravedi, Mario Bontempelli, Giuseppe Remuzzi
CJASN Jul 2006, 1 (4) 738-748; DOI: 10.2215/CJN.01080905

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Rituximab for Idiopathic Membranous Nephropathy: Who Can Benefit?
Piero Ruggenenti, Carlos Chiurchiu, Mauro Abbate, Annalisa Perna, Paolo Cravedi, Mario Bontempelli, Giuseppe Remuzzi
CJASN Jul 2006, 1 (4) 738-748; DOI: 10.2215/CJN.01080905
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Cited By...

  • Clinical Response and Pattern of B cell Suppression with Single Low Dose Rituximab in Nephrology
  • Treatment of Idiopathic Membranous Nephropathy
  • Rituximab in Children with Resistant Idiopathic Nephrotic Syndrome
  • Circulating Anti-PLA2R Autoantibodies to Monitor Immunological Activity in Membranous Nephropathy
  • Short-Term Effects of Rituximab in Children with Steroid- and Calcineurin-Dependent Nephrotic Syndrome: A Randomized Controlled Trial
  • Role of Rituximab Therapy in Glomerulonephritis
  • Novel B Cell Therapeutic Targets in Transplantation and Immune-Mediated Glomerular Diseases
  • Successful Treatment of Membranous Glomerulonephritis with Rituximab in Calcineurin Inhibitor-Dependent Patients
  • Overcoming Calcineurin Dependence in Membranous Nephropathy: Is Rituximab the Answer?
  • Rituximab Therapy for Membranous Nephropathy: A Systematic Review
  • Hepatitis C Infection and Chronic Renal Diseases
  • Idiopathic Membranous Nephropathy: Diagnosis and Treatment
  • Titrating Rituximab to Circulating B Cells to Optimize Lymphocytolytic Therapy in Idiopathic Membranous Nephropathy
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