Low-and high-molecular-weight urinary proteins as predictors of response to rituximab in patients with membranous nephropathy: A prospective study

Maria Irazabal Mira, Alfonso Eirin, John C Lieske, Laurence H. Beck, Sanjeev M Sethi, Timothy M. Borland, John J. Dillon, Patrick H. Nachman, Samih H. Nasr, Lynn D. Cornell, Nelson Leung, Daniel C. Cattran, Fernando Custodio Fervenza

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)137-146
Number of pages10
JournalNephrology Dialysis Transplantation
Volume28
Issue number1
DOIs
StatePublished - Jan 2013

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Membranous Glomerulonephritis
Proteinuria
Molecular Weight
Prospective Studies
Phospholipases
Albumins
Biomarkers
Proteins
Cellular Retinol-Binding Proteins
Linear Models
Immunoglobulin G
Regression Analysis
Rituximab
Antibodies

Keywords

  • membranous nephropathy
  • rituximab
  • urinary proteins

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Low-and high-molecular-weight urinary proteins as predictors of response to rituximab in patients with membranous nephropathy : A prospective study. / Irazabal Mira, Maria; Eirin, Alfonso; Lieske, John C; Beck, Laurence H.; Sethi, Sanjeev M; Borland, Timothy M.; Dillon, John J.; Nachman, Patrick H.; Nasr, Samih H.; Cornell, Lynn D.; Leung, Nelson; Cattran, Daniel C.; Fervenza, Fernando Custodio.

In: Nephrology Dialysis Transplantation, Vol. 28, No. 1, 01.2013, p. 137-146.

Research output: Contribution to journalArticle

Irazabal Mira, Maria ; Eirin, Alfonso ; Lieske, John C ; Beck, Laurence H. ; Sethi, Sanjeev M ; Borland, Timothy M. ; Dillon, John J. ; Nachman, Patrick H. ; Nasr, Samih H. ; Cornell, Lynn D. ; Leung, Nelson ; Cattran, Daniel C. ; Fervenza, Fernando Custodio. / Low-and high-molecular-weight urinary proteins as predictors of response to rituximab in patients with membranous nephropathy : A prospective study. In: Nephrology Dialysis Transplantation. 2013 ; Vol. 28, No. 1. pp. 137-146.
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title = "Low-and high-molecular-weight urinary proteins as predictors of response to rituximab in patients with membranous nephropathy: A prospective study",
abstract = "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.",
keywords = "membranous nephropathy, rituximab, urinary proteins",
author = "{Irazabal Mira}, Maria and Alfonso Eirin and Lieske, {John C} and Beck, {Laurence H.} and Sethi, {Sanjeev M} and Borland, {Timothy M.} and Dillon, {John J.} and Nachman, {Patrick H.} and Nasr, {Samih H.} and Cornell, {Lynn D.} and Nelson Leung and Cattran, {Daniel C.} and Fervenza, {Fernando Custodio}",
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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 Mira, Maria

AU - Eirin, Alfonso

AU - Lieske, John C

AU - Beck, Laurence H.

AU - Sethi, Sanjeev M

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 Custodio

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.

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KW - rituximab

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