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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^*,

^* Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Mario Negri Institute for Pharmacological Research, and Units of Nephrology and Immunohematology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy

Address correspondence to: Dr. Piero Ruggenenti, "Mario Negri" Institute for Pharmacological Research, Via Gavazzeni, 11, 24125 Bergamo, Italy. Phone: +39-035-319-888; Fax: +39-035-319-331; E-mail: manuelap{at}marionegri.it

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 ß coefficients (SßC). Glomerular (SßC = 0.48, P = 0.049) and tubulointerstitial (TI) scores (SßC = 0.61, P = 0.003) predicted the outcome. Among glomerular and TI score components, tubular atrophy (SßC = 0.59, P = 0.003) and interstitial fibrosis (SßC = 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.

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