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Factors associated with the progression of mesangial lesions in IgA nephropathy: A comparative analysis of renal re-biopsies

OBJECTIVES: IgA nephropathy (IgAN) is the most common primary glomerular disease, and is the leading cause of chronic renal failure. Because mesangial lesions are the main pathological changes seen in IgAN, we investigated factors associated with the progression of mesangial lesions in IgAN. METHODS...

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Autores principales: Li, Yetong, Jiang, Shimin, Gao, Hongmei, Yang, Yue, Liu, Xiaorong, Li, Wenge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719920/
https://www.ncbi.nlm.nih.gov/pubmed/36479219
http://dx.doi.org/10.3389/fendo.2022.1004289
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author Li, Yetong
Jiang, Shimin
Gao, Hongmei
Yang, Yue
Liu, Xiaorong
Li, Wenge
author_facet Li, Yetong
Jiang, Shimin
Gao, Hongmei
Yang, Yue
Liu, Xiaorong
Li, Wenge
author_sort Li, Yetong
collection PubMed
description OBJECTIVES: IgA nephropathy (IgAN) is the most common primary glomerular disease, and is the leading cause of chronic renal failure. Because mesangial lesions are the main pathological changes seen in IgAN, we investigated factors associated with the progression of mesangial lesions in IgAN. METHODS: We enrolled participants with IgAN who underwent repeat renal biopsies. Based on the progression of mesangial proliferative lesions, the participants were divided into progressive and stable groups. The progression group included participants with a ratio of mesangial cell proliferation score ≥ 1.1 (i.e., proliferation of > 10%) in the second biopsy specimen compared to the first biopsy specimen. The stable group included participants who did not fulfill the aforementioned criteria. We recorded the laboratory parameters, expression of renin-angiotensin system (RAS) receptors (angiotensin II type 1 receptor [AT1R], angiotensin II type 2 receptor [AT2R], Mas receptor [MasR], and the Mas-related G protein-coupled receptor, member D [MrgD]) and mesangial matrix proteins (collagen [Col] IV, fibronectin [FN] and laminin) at the first and second renal biopsies, and the use of immunosuppressive therapy and/or RAS blockers after the first biopsy. RESULTS: We enrolled 24 patients with IgAN who underwent repeat renal biopsies. Half of patients showed progression of mesangial lesions on repeat renal biopsy after a median of 4.3 (1–6) years. The progression group had significantly higher expression levels of AT1R and mesangial matrix proteins (Col IV and FN), and significantly lower expression of AT2R and MasR, compared to the stable group. Multivariate analysis showed that the use of RAS blockers (hazard ratio [HR], 0.27; 95% CI, 0.08–0.97; p < 0.05) and the level of proteinuria (HR, 1.8; 95% CI, 1.04–3.12; p < 0.05) were associated with progression of mesangial lesions. Additionally, the progression group exhibited a more rapid decline of renal function compared to the stable group (0.38 and 0.012 ml/min/1.73 m(2)/month, respectively; p = 0.004). CONCLUSIONS: Continuous activation of the intrarenal RAS and massive proteinuria correlate with histological progression of mesangial lesions in IgAN patients, which may further accelerate the deterioration of renal function.
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spelling pubmed-97199202022-12-06 Factors associated with the progression of mesangial lesions in IgA nephropathy: A comparative analysis of renal re-biopsies Li, Yetong Jiang, Shimin Gao, Hongmei Yang, Yue Liu, Xiaorong Li, Wenge Front Endocrinol (Lausanne) Endocrinology OBJECTIVES: IgA nephropathy (IgAN) is the most common primary glomerular disease, and is the leading cause of chronic renal failure. Because mesangial lesions are the main pathological changes seen in IgAN, we investigated factors associated with the progression of mesangial lesions in IgAN. METHODS: We enrolled participants with IgAN who underwent repeat renal biopsies. Based on the progression of mesangial proliferative lesions, the participants were divided into progressive and stable groups. The progression group included participants with a ratio of mesangial cell proliferation score ≥ 1.1 (i.e., proliferation of > 10%) in the second biopsy specimen compared to the first biopsy specimen. The stable group included participants who did not fulfill the aforementioned criteria. We recorded the laboratory parameters, expression of renin-angiotensin system (RAS) receptors (angiotensin II type 1 receptor [AT1R], angiotensin II type 2 receptor [AT2R], Mas receptor [MasR], and the Mas-related G protein-coupled receptor, member D [MrgD]) and mesangial matrix proteins (collagen [Col] IV, fibronectin [FN] and laminin) at the first and second renal biopsies, and the use of immunosuppressive therapy and/or RAS blockers after the first biopsy. RESULTS: We enrolled 24 patients with IgAN who underwent repeat renal biopsies. Half of patients showed progression of mesangial lesions on repeat renal biopsy after a median of 4.3 (1–6) years. The progression group had significantly higher expression levels of AT1R and mesangial matrix proteins (Col IV and FN), and significantly lower expression of AT2R and MasR, compared to the stable group. Multivariate analysis showed that the use of RAS blockers (hazard ratio [HR], 0.27; 95% CI, 0.08–0.97; p < 0.05) and the level of proteinuria (HR, 1.8; 95% CI, 1.04–3.12; p < 0.05) were associated with progression of mesangial lesions. Additionally, the progression group exhibited a more rapid decline of renal function compared to the stable group (0.38 and 0.012 ml/min/1.73 m(2)/month, respectively; p = 0.004). CONCLUSIONS: Continuous activation of the intrarenal RAS and massive proteinuria correlate with histological progression of mesangial lesions in IgAN patients, which may further accelerate the deterioration of renal function. Frontiers Media S.A. 2022-11-21 /pmc/articles/PMC9719920/ /pubmed/36479219 http://dx.doi.org/10.3389/fendo.2022.1004289 Text en Copyright © 2022 Li, Jiang, Gao, Yang, Liu and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Li, Yetong
Jiang, Shimin
Gao, Hongmei
Yang, Yue
Liu, Xiaorong
Li, Wenge
Factors associated with the progression of mesangial lesions in IgA nephropathy: A comparative analysis of renal re-biopsies
title Factors associated with the progression of mesangial lesions in IgA nephropathy: A comparative analysis of renal re-biopsies
title_full Factors associated with the progression of mesangial lesions in IgA nephropathy: A comparative analysis of renal re-biopsies
title_fullStr Factors associated with the progression of mesangial lesions in IgA nephropathy: A comparative analysis of renal re-biopsies
title_full_unstemmed Factors associated with the progression of mesangial lesions in IgA nephropathy: A comparative analysis of renal re-biopsies
title_short Factors associated with the progression of mesangial lesions in IgA nephropathy: A comparative analysis of renal re-biopsies
title_sort factors associated with the progression of mesangial lesions in iga nephropathy: a comparative analysis of renal re-biopsies
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719920/
https://www.ncbi.nlm.nih.gov/pubmed/36479219
http://dx.doi.org/10.3389/fendo.2022.1004289
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