TY - JOUR
T1 - Low-and high-molecular-weight urinary proteins as predictors of response to rituximab in patients with membranous nephropathy
T2 - A prospective study
AU - Irazabal, Maria V.
AU - Eirin, Alfonso
AU - Lieske, John
AU - Beck, Laurence H.
AU - Sethi, Sanjeev
AU - Borland, Timothy M.
AU - Dillon, John J.
AU - Nachman, Patrick H.
AU - Nasr, Samih H.
AU - Cornell, Lynn D.
AU - Leung, Nelson
AU - Cattran, Daniel C.
AU - Fervenza, Fernando C.
N1 - Funding Information:
Acknowledgments. The authors thank Mrs Lori Riess, for her outstanding role as research coordinator for the study. The study was supported by an unrestricted research grant from Genentech Inc., South San Francisco, CA, Biogen Idec, San Diego CA, the Department of Laboratory Medicine and Pathology, Mayo Clinic, the Fulk Family Foundation (FCF) and by a UL1-RR24150 grant to the Center for Translational Science Activities, Mayo Clinic. The results presented in this paper have not been published previously in whole or part, except in abstract format at the American Society of Nephrology meeting in Philadelphia, PA, November 2011.
PY - 2013/1
Y1 - 2013/1
N2 - Background. Selective urinary biomarkers have been considered superior to total proteinuria in predicting response to treatment and outcome in patients with membranous nephropathy (MN). Methods. We prospectively tested whether urinary (U) excretion of retinol-binding protein (RBP), α1-microglobulin (α1M), albumin, immunoglobulinIgG and IgM and/or anti-phospholipase 2 receptor (PLA2R) levels could predict response to rituximab (RTX) therapy better than standard measures in MN. We also correlated changes in antibodies to PLA2R with these urinary biomarkers. Results . Twenty patients with MN and proteinuria (P) >5 g/24 h received RTX (375 mg/m 2 × 4) and at 12 months, 1 patient was in complete remission (CR), 9 were in partial remission (PR), 5 had a limited response (LR) and 4 were non-responders (NR). At 24 months, CR occurred in 4, PR in 12, LR in 1, NR in 2 and 1 patient relapsed. By simple linear regression analysis, UIgG at baseline (mg/24 h) was a significant predictor of change in proteinuria at 12 months (Δ urinary protein) (P = 0.04). In addition, fractional excretion (FE) of IgG, urinary alpha 1 microglobulin (Uα1M) (mg/24 h) and URBP (μg/24 h) were also predictors of response (P = 0.05, 0.04, and 0.03, respectively). On the other hand, UIgM, FEIgM, albumin and FE albumin did not predict response (P = 0.10, 0.27, 0.22 and 0.20, respectively). However, when Results were analyzed in relation to proteinuria at 24 months, none of the U markers that predicted response at 12 m could predict response at 24 m (P = 0.55, 0.42, 0.29 and 0.20). Decline in anti-PLA2R levels was associated with and often preceded urinary biomarker response but positivity at baseline was not a predictor of proteinuria response. Conclusions. The Results suggest that in patients with MN, quantification of low-, medium-and high-molecular-weight urinary proteins may be associated with rate of response to RTX, but do not correlate with longer term outcomes.
AB - Background. Selective urinary biomarkers have been considered superior to total proteinuria in predicting response to treatment and outcome in patients with membranous nephropathy (MN). Methods. We prospectively tested whether urinary (U) excretion of retinol-binding protein (RBP), α1-microglobulin (α1M), albumin, immunoglobulinIgG and IgM and/or anti-phospholipase 2 receptor (PLA2R) levels could predict response to rituximab (RTX) therapy better than standard measures in MN. We also correlated changes in antibodies to PLA2R with these urinary biomarkers. Results . Twenty patients with MN and proteinuria (P) >5 g/24 h received RTX (375 mg/m 2 × 4) and at 12 months, 1 patient was in complete remission (CR), 9 were in partial remission (PR), 5 had a limited response (LR) and 4 were non-responders (NR). At 24 months, CR occurred in 4, PR in 12, LR in 1, NR in 2 and 1 patient relapsed. By simple linear regression analysis, UIgG at baseline (mg/24 h) was a significant predictor of change in proteinuria at 12 months (Δ urinary protein) (P = 0.04). In addition, fractional excretion (FE) of IgG, urinary alpha 1 microglobulin (Uα1M) (mg/24 h) and URBP (μg/24 h) were also predictors of response (P = 0.05, 0.04, and 0.03, respectively). On the other hand, UIgM, FEIgM, albumin and FE albumin did not predict response (P = 0.10, 0.27, 0.22 and 0.20, respectively). However, when Results were analyzed in relation to proteinuria at 24 months, none of the U markers that predicted response at 12 m could predict response at 24 m (P = 0.55, 0.42, 0.29 and 0.20). Decline in anti-PLA2R levels was associated with and often preceded urinary biomarker response but positivity at baseline was not a predictor of proteinuria response. Conclusions. The Results suggest that in patients with MN, quantification of low-, medium-and high-molecular-weight urinary proteins may be associated with rate of response to RTX, but do not correlate with longer term outcomes.
KW - membranous nephropathy
KW - rituximab
KW - urinary proteins
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U2 - 10.1093/ndt/gfs379
DO - 10.1093/ndt/gfs379
M3 - Article
C2 - 22987142
AN - SCOPUS:84872254697
SN - 0931-0509
VL - 28
SP - 137
EP - 146
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
IS - 1
ER -