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Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression
BACKGROUND: Hypertension is a multi-factorial disease of increasing prevalence and a major risk factor for cardiovascular mortality even in the presence of adequate treatment. Progression of cardiovascular disease (CVD) occurs frequently during chronic renin-angiotensin-system (RAS) suppression, and...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715311/ https://www.ncbi.nlm.nih.gov/pubmed/26772976 http://dx.doi.org/10.1186/s12933-016-0331-7 |
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author | Gonzalez-Calero, Laura Martin-Lorenzo, Marta de la Cuesta, Fernando Maroto, Aroa S. Baldan-Martin, Montserrat Ruiz-Hurtado, Gema Pulido-Olmo, Helena Segura, Julian Barderas, Maria G. Ruilope, Luis M. Vivanco, Fernando Alvarez-Llamas, Gloria |
author_facet | Gonzalez-Calero, Laura Martin-Lorenzo, Marta de la Cuesta, Fernando Maroto, Aroa S. Baldan-Martin, Montserrat Ruiz-Hurtado, Gema Pulido-Olmo, Helena Segura, Julian Barderas, Maria G. Ruilope, Luis M. Vivanco, Fernando Alvarez-Llamas, Gloria |
author_sort | Gonzalez-Calero, Laura |
collection | PubMed |
description | BACKGROUND: Hypertension is a multi-factorial disease of increasing prevalence and a major risk factor for cardiovascular mortality even in the presence of adequate treatment. Progression of cardiovascular disease (CVD) occurs frequently during chronic renin-angiotensin-system (RAS) suppression, and albuminuria is a marker of CV risk. High prevalence of albuminuria in treated hypertensive patients has been demonstrated, but there are no available markers able to predict evolution. The aim of this study was the identification of novel indicators of albuminuria progression measurable in urine of diabetic and non-diabetic patients. METHODS: 1143 hypertensive patients under chronic treatment were followed for a minimum period of 3 years. Among them, 105 diabetic and non-diabetic patients were selected and classified in three groups according to albuminuria development during follow-up: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Differential urine analysis was performed by 2D gel electrophoresis (2D-DIGE) and further confirmed by liquid chromatography-mass spectrometry. Non-parametric statistical tests were applied. RESULTS: CD59 glycoprotein and alpha-1 antitrypsin (AAT) resulted already altered in patients developing albuminuria de novo, with a similar response in those with maintained albuminuria. A prospective study in a sub-group of normoalbuminuric patients who were clinically followed up for at least 1 year from urine sampling, revealed CD59 and AAT proteins significantly varied in the urine collected from normoalbuminurics who will negatively progress, serving as predictors of future albuminuria development. CONCLUSIONS: CD59 and AAT proteins are significantly altered in hypertensive patients developing albuminuria. Interestingly, CD59 and AAT are able to predict, in normoalbuminuric individuals, who will develop albuminuria in the future, being potential predictors of vascular damage and CV risk. These findings contribute to early identify patients at risk of developing albuminuria even when this classical predictor is still in the normal range, constituting a novel strategy towards a prompt and more efficient therapeutic intervention with better outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-016-0331-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4715311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47153112016-01-17 Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression Gonzalez-Calero, Laura Martin-Lorenzo, Marta de la Cuesta, Fernando Maroto, Aroa S. Baldan-Martin, Montserrat Ruiz-Hurtado, Gema Pulido-Olmo, Helena Segura, Julian Barderas, Maria G. Ruilope, Luis M. Vivanco, Fernando Alvarez-Llamas, Gloria Cardiovasc Diabetol Original Investigation BACKGROUND: Hypertension is a multi-factorial disease of increasing prevalence and a major risk factor for cardiovascular mortality even in the presence of adequate treatment. Progression of cardiovascular disease (CVD) occurs frequently during chronic renin-angiotensin-system (RAS) suppression, and albuminuria is a marker of CV risk. High prevalence of albuminuria in treated hypertensive patients has been demonstrated, but there are no available markers able to predict evolution. The aim of this study was the identification of novel indicators of albuminuria progression measurable in urine of diabetic and non-diabetic patients. METHODS: 1143 hypertensive patients under chronic treatment were followed for a minimum period of 3 years. Among them, 105 diabetic and non-diabetic patients were selected and classified in three groups according to albuminuria development during follow-up: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Differential urine analysis was performed by 2D gel electrophoresis (2D-DIGE) and further confirmed by liquid chromatography-mass spectrometry. Non-parametric statistical tests were applied. RESULTS: CD59 glycoprotein and alpha-1 antitrypsin (AAT) resulted already altered in patients developing albuminuria de novo, with a similar response in those with maintained albuminuria. A prospective study in a sub-group of normoalbuminuric patients who were clinically followed up for at least 1 year from urine sampling, revealed CD59 and AAT proteins significantly varied in the urine collected from normoalbuminurics who will negatively progress, serving as predictors of future albuminuria development. CONCLUSIONS: CD59 and AAT proteins are significantly altered in hypertensive patients developing albuminuria. Interestingly, CD59 and AAT are able to predict, in normoalbuminuric individuals, who will develop albuminuria in the future, being potential predictors of vascular damage and CV risk. These findings contribute to early identify patients at risk of developing albuminuria even when this classical predictor is still in the normal range, constituting a novel strategy towards a prompt and more efficient therapeutic intervention with better outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-016-0331-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-16 /pmc/articles/PMC4715311/ /pubmed/26772976 http://dx.doi.org/10.1186/s12933-016-0331-7 Text en © Gonzalez-Calero et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Original Investigation Gonzalez-Calero, Laura Martin-Lorenzo, Marta de la Cuesta, Fernando Maroto, Aroa S. Baldan-Martin, Montserrat Ruiz-Hurtado, Gema Pulido-Olmo, Helena Segura, Julian Barderas, Maria G. Ruilope, Luis M. Vivanco, Fernando Alvarez-Llamas, Gloria Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression |
title | Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression |
title_full | Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression |
title_fullStr | Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression |
title_full_unstemmed | Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression |
title_short | Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression |
title_sort | urinary alpha-1 antitrypsin and cd59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715311/ https://www.ncbi.nlm.nih.gov/pubmed/26772976 http://dx.doi.org/10.1186/s12933-016-0331-7 |
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