TY - JOUR
T1 - Rituximab for idiopathic membranous nephropathy
T2 - who can benefit?
AU - Ruggenenti, Piero
AU - Chiurchiu, Carlos
AU - Abbate, Mauro
AU - Perna, Annalisa
AU - Cravedi, Paolo
AU - Bontempelli, Mario
AU - Remuzzi, Giuseppe
PY - 2006/7
Y1 - 2006/7
N2 - 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 beta coefficients (SbetaC). Glomerular (SbetaC = 0.48, P = 0.049) and tubulointerstitial (TI) scores (SbetaC = 0.61, P = 0.003) predicted the outcome. Among glomerular and TI score components, tubular atrophy (SbetaC = 0.59, P = 0.003) and interstitial fibrosis (SbetaC = 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 > or = 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.
AB - 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 beta coefficients (SbetaC). Glomerular (SbetaC = 0.48, P = 0.049) and tubulointerstitial (TI) scores (SbetaC = 0.61, P = 0.003) predicted the outcome. Among glomerular and TI score components, tubular atrophy (SbetaC = 0.59, P = 0.003) and interstitial fibrosis (SbetaC = 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 > or = 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.
UR - http://www.scopus.com/inward/record.url?scp=34548443784&partnerID=8YFLogxK
U2 - 10.2215/CJN.01080905
DO - 10.2215/CJN.01080905
M3 - Article
C2 - 17699281
AN - SCOPUS:34548443784
SN - 1555-9041
VL - 1
SP - 738
EP - 748
JO - Clinical journal of the American Society of Nephrology : CJASN
JF - Clinical journal of the American Society of Nephrology : CJASN
IS - 4
ER -