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Role of phospholipase A(2) receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy

BACKGROUND: Membranous nephropathy (MN) is an autoimmune disease induced by circulating antibodies against the podocyte protein phospholipase A(2) receptor 1 (PLA(2)R1-ab) in 80% of patients and represents the leading cause of nephrotic syndrome in adults. PLA(2)R1-ab levels correlate with disease a...

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Autores principales: Mahmud, Maida, Pinnschmidt, Hans O., Reinhard, Linda, Harendza, Sigrid, Wiech, Thorsten, Stahl, Rolf A. K., Hoxha, Elion
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733455/
https://www.ncbi.nlm.nih.gov/pubmed/31498806
http://dx.doi.org/10.1371/journal.pone.0221293
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author Mahmud, Maida
Pinnschmidt, Hans O.
Reinhard, Linda
Harendza, Sigrid
Wiech, Thorsten
Stahl, Rolf A. K.
Hoxha, Elion
author_facet Mahmud, Maida
Pinnschmidt, Hans O.
Reinhard, Linda
Harendza, Sigrid
Wiech, Thorsten
Stahl, Rolf A. K.
Hoxha, Elion
author_sort Mahmud, Maida
collection PubMed
description BACKGROUND: Membranous nephropathy (MN) is an autoimmune disease induced by circulating antibodies against the podocyte protein phospholipase A(2) receptor 1 (PLA(2)R1-ab) in 80% of patients and represents the leading cause of nephrotic syndrome in adults. PLA(2)R1-ab levels correlate with disease activity and treatment response. However, their predictive role for long-term renal outcome is not clear. METHODS: The aim of this prospective observational multicenter study was to investigate the predictive role of PLA(2)R1-ab levels at the time of diagnosis for long-term outcome in a cohort of 243 patients with newly diagnosed biopsy-proven PLA(2)R1-associated MN. Statistical analyses included Cox proportional hazard models. The primary study endpoint was defined prior to data collection as doubling of serum creatinine or development of end-stage renal disease. RESULTS: During the median follow-up time of 48 months, 36 (15%) patients reached the study endpoint. Independent predictors for reaching the study endpoint were baseline PLA(2)R1-ab levels (HR = 1.36, 95%CI 1.11–1.66, p = 0.01), percentage of tubular atrophy and interstitial fibrosis (HR = 1.32, 95%CI 1.03–1.68, p = 0.03), PLA(2)R1-ab relapse during follow-up (HR = 3.22, 95%CI 1.36–7.60, p = 0.01), and relapse of proteinuria (HR = 2.60, 95%CI 1.17–5.79, p = 0.02). Fifty-four (22%) patients received no immunosuppressive treatment during the study, in 41 (76%) of them PLA(2)R1-ab spontaneously disappeared during follow-up, 29 (54%) patients had a complete remission of proteinuria, and 19 (35%) had a partial remission. Patients not treated with immunosuppression were more often females and had lower PLA(2)R1-ab levels, proteinuria, and serum creatinine at baseline compared to patients receiving immunosuppression. However, no conclusion on the efficacy of immunosuppressive therapies can be made, since this was not a randomized controlled study and treatment decisions were not made per-protocol. CONCLUSIONS: PLA(2)R1-ab levels are, in addition to pre-existing renal damage, predictive factors for long-term outcome and should therefore be considered when deciding the treatment of patients with MN.
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spelling pubmed-67334552019-09-20 Role of phospholipase A(2) receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy Mahmud, Maida Pinnschmidt, Hans O. Reinhard, Linda Harendza, Sigrid Wiech, Thorsten Stahl, Rolf A. K. Hoxha, Elion PLoS One Research Article BACKGROUND: Membranous nephropathy (MN) is an autoimmune disease induced by circulating antibodies against the podocyte protein phospholipase A(2) receptor 1 (PLA(2)R1-ab) in 80% of patients and represents the leading cause of nephrotic syndrome in adults. PLA(2)R1-ab levels correlate with disease activity and treatment response. However, their predictive role for long-term renal outcome is not clear. METHODS: The aim of this prospective observational multicenter study was to investigate the predictive role of PLA(2)R1-ab levels at the time of diagnosis for long-term outcome in a cohort of 243 patients with newly diagnosed biopsy-proven PLA(2)R1-associated MN. Statistical analyses included Cox proportional hazard models. The primary study endpoint was defined prior to data collection as doubling of serum creatinine or development of end-stage renal disease. RESULTS: During the median follow-up time of 48 months, 36 (15%) patients reached the study endpoint. Independent predictors for reaching the study endpoint were baseline PLA(2)R1-ab levels (HR = 1.36, 95%CI 1.11–1.66, p = 0.01), percentage of tubular atrophy and interstitial fibrosis (HR = 1.32, 95%CI 1.03–1.68, p = 0.03), PLA(2)R1-ab relapse during follow-up (HR = 3.22, 95%CI 1.36–7.60, p = 0.01), and relapse of proteinuria (HR = 2.60, 95%CI 1.17–5.79, p = 0.02). Fifty-four (22%) patients received no immunosuppressive treatment during the study, in 41 (76%) of them PLA(2)R1-ab spontaneously disappeared during follow-up, 29 (54%) patients had a complete remission of proteinuria, and 19 (35%) had a partial remission. Patients not treated with immunosuppression were more often females and had lower PLA(2)R1-ab levels, proteinuria, and serum creatinine at baseline compared to patients receiving immunosuppression. However, no conclusion on the efficacy of immunosuppressive therapies can be made, since this was not a randomized controlled study and treatment decisions were not made per-protocol. CONCLUSIONS: PLA(2)R1-ab levels are, in addition to pre-existing renal damage, predictive factors for long-term outcome and should therefore be considered when deciding the treatment of patients with MN. Public Library of Science 2019-09-09 /pmc/articles/PMC6733455/ /pubmed/31498806 http://dx.doi.org/10.1371/journal.pone.0221293 Text en © 2019 Mahmud et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Mahmud, Maida
Pinnschmidt, Hans O.
Reinhard, Linda
Harendza, Sigrid
Wiech, Thorsten
Stahl, Rolf A. K.
Hoxha, Elion
Role of phospholipase A(2) receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy
title Role of phospholipase A(2) receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy
title_full Role of phospholipase A(2) receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy
title_fullStr Role of phospholipase A(2) receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy
title_full_unstemmed Role of phospholipase A(2) receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy
title_short Role of phospholipase A(2) receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy
title_sort role of phospholipase a(2) receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733455/
https://www.ncbi.nlm.nih.gov/pubmed/31498806
http://dx.doi.org/10.1371/journal.pone.0221293
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