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Pre-Analytical and Clinical Validation of a Dried Blood Spot Assay for Asymmetric Dimethylarginine and L-Arginine
Asymmetric dimethylarginine (ADMA) inhibits nitric oxide (NO) synthesis. It is a risk marker for cardiovascular events and mortality in patients with cardiometabolic diseases and in population-based studies. Plasma or serum analysis of ADMA may be hampered by pre-analytical sample handling. We valid...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230730/ https://www.ncbi.nlm.nih.gov/pubmed/32283799 http://dx.doi.org/10.3390/jcm9041072 |
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author | Hannemann, Juliane Roskam, Thore I. Eilermann, Ina Siques, Patricia Brito, Julio Böger, Rainer |
author_facet | Hannemann, Juliane Roskam, Thore I. Eilermann, Ina Siques, Patricia Brito, Julio Böger, Rainer |
author_sort | Hannemann, Juliane |
collection | PubMed |
description | Asymmetric dimethylarginine (ADMA) inhibits nitric oxide (NO) synthesis. It is a risk marker for cardiovascular events and mortality in patients with cardiometabolic diseases and in population-based studies. Plasma or serum analysis of ADMA may be hampered by pre-analytical sample handling. We validated a dried blood spot (DBS) assay for ADMA and L-arginine and show here that this assay has excellent variabilities and reproducibilities. Filter paper is impregnated with the arginase inhibitor nor-NOHA (N(ω)-hydroxy-nor-Arginine) to avoid L-arginine degradation. Clinical validation of this DBS assay confirms elevated ADMA concentration in hemodialysis patients as compared to healthy controls, higher ADMA concentrations in men versus women, and elevated L-arginine concentration in subjects supplemented with L-arginine. The DBS assay was used in a cohort study involving 100 primarily healthy subjects in the Andean region to assess the impact of chronic intermittent hypoxia on ADMA and L-arginine; ADMA DBS concentration at sea level was prospectively associated with pulmonary hypertension after six months of exposure to 3500 m. In a cohort of 753 individuals, L-arginine/ADMA ratio significantly decreased with increasing number of traditional cardiovascular risk factors. Analysis of ADMA and L-arginine in DBS is a reliable and reproducible method for quantitation of these markers in field studies. |
format | Online Article Text |
id | pubmed-7230730 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72307302020-05-22 Pre-Analytical and Clinical Validation of a Dried Blood Spot Assay for Asymmetric Dimethylarginine and L-Arginine Hannemann, Juliane Roskam, Thore I. Eilermann, Ina Siques, Patricia Brito, Julio Böger, Rainer J Clin Med Article Asymmetric dimethylarginine (ADMA) inhibits nitric oxide (NO) synthesis. It is a risk marker for cardiovascular events and mortality in patients with cardiometabolic diseases and in population-based studies. Plasma or serum analysis of ADMA may be hampered by pre-analytical sample handling. We validated a dried blood spot (DBS) assay for ADMA and L-arginine and show here that this assay has excellent variabilities and reproducibilities. Filter paper is impregnated with the arginase inhibitor nor-NOHA (N(ω)-hydroxy-nor-Arginine) to avoid L-arginine degradation. Clinical validation of this DBS assay confirms elevated ADMA concentration in hemodialysis patients as compared to healthy controls, higher ADMA concentrations in men versus women, and elevated L-arginine concentration in subjects supplemented with L-arginine. The DBS assay was used in a cohort study involving 100 primarily healthy subjects in the Andean region to assess the impact of chronic intermittent hypoxia on ADMA and L-arginine; ADMA DBS concentration at sea level was prospectively associated with pulmonary hypertension after six months of exposure to 3500 m. In a cohort of 753 individuals, L-arginine/ADMA ratio significantly decreased with increasing number of traditional cardiovascular risk factors. Analysis of ADMA and L-arginine in DBS is a reliable and reproducible method for quantitation of these markers in field studies. MDPI 2020-04-09 /pmc/articles/PMC7230730/ /pubmed/32283799 http://dx.doi.org/10.3390/jcm9041072 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hannemann, Juliane Roskam, Thore I. Eilermann, Ina Siques, Patricia Brito, Julio Böger, Rainer Pre-Analytical and Clinical Validation of a Dried Blood Spot Assay for Asymmetric Dimethylarginine and L-Arginine |
title | Pre-Analytical and Clinical Validation of a Dried Blood Spot Assay for Asymmetric Dimethylarginine and L-Arginine |
title_full | Pre-Analytical and Clinical Validation of a Dried Blood Spot Assay for Asymmetric Dimethylarginine and L-Arginine |
title_fullStr | Pre-Analytical and Clinical Validation of a Dried Blood Spot Assay for Asymmetric Dimethylarginine and L-Arginine |
title_full_unstemmed | Pre-Analytical and Clinical Validation of a Dried Blood Spot Assay for Asymmetric Dimethylarginine and L-Arginine |
title_short | Pre-Analytical and Clinical Validation of a Dried Blood Spot Assay for Asymmetric Dimethylarginine and L-Arginine |
title_sort | pre-analytical and clinical validation of a dried blood spot assay for asymmetric dimethylarginine and l-arginine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230730/ https://www.ncbi.nlm.nih.gov/pubmed/32283799 http://dx.doi.org/10.3390/jcm9041072 |
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