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Acute Kidney Injury Urinary Biomarker Time-Courses
Factors which modify the excretion profiles of acute kidney injury biomarkers are difficult to measure. To facilitate biomarker choice and interpretation we modelled key modifying factors: extent of hyperfiltration or reduced glomerular filtration rate, structural damage, and reduced nephron number....
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090122/ https://www.ncbi.nlm.nih.gov/pubmed/25006799 http://dx.doi.org/10.1371/journal.pone.0101288 |
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author | Pickering, John W. Endre, Zoltán H. |
author_facet | Pickering, John W. Endre, Zoltán H. |
author_sort | Pickering, John W. |
collection | PubMed |
description | Factors which modify the excretion profiles of acute kidney injury biomarkers are difficult to measure. To facilitate biomarker choice and interpretation we modelled key modifying factors: extent of hyperfiltration or reduced glomerular filtration rate, structural damage, and reduced nephron number. The time-courses of pre-formed, induced (upregulated), and filtered biomarker concentrations were modelled in single nephrons, then combined to construct three multiple-nephron models: a healthy kidney with normal nephron number, a non-diabetic hyperfiltering kidney with reduced nephron number but maintained total glomerular filtration rate, and a chronic kidney disease kidney with reduced nephron number and reduced glomerular filtration rate. Time-courses for each model were derived for acute kidney injury scenarios of structural damage and/or reduced nephron number. The model predicted that pre-formed biomarkers would respond quickest to injury with a brief period of elevation, which would be easily missed in clinical scenarios. Induced biomarker time-courses would be influenced by biomarker-specific physiology and the balance between insult severity (which increased single nephron excretion), the number of remaining nephrons (reduced total excretion), and the extent of glomerular filtration rate reduction (increased concentration). Filtered biomarkers have the longest time-course because plasma levels increased following glomerular filtration rate decrease. Peak concentration and profile depended on the extent of damage to the reabsorption mechanism and recovery rate. Rapid recovery may be detected through a rapid reduction in urinary concentration. For all biomarkers, impaired hyperfiltration substantially increased concentration, especially with chronic kidney disease. For clinical validation of these model-derived predictions the clinical biomarker of choice will depend on timing in relation to renal insult and interpretation will require the pre-insult nephron number (renal mass) and detection of hyperfiltration. |
format | Online Article Text |
id | pubmed-4090122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40901222014-07-14 Acute Kidney Injury Urinary Biomarker Time-Courses Pickering, John W. Endre, Zoltán H. PLoS One Research Article Factors which modify the excretion profiles of acute kidney injury biomarkers are difficult to measure. To facilitate biomarker choice and interpretation we modelled key modifying factors: extent of hyperfiltration or reduced glomerular filtration rate, structural damage, and reduced nephron number. The time-courses of pre-formed, induced (upregulated), and filtered biomarker concentrations were modelled in single nephrons, then combined to construct three multiple-nephron models: a healthy kidney with normal nephron number, a non-diabetic hyperfiltering kidney with reduced nephron number but maintained total glomerular filtration rate, and a chronic kidney disease kidney with reduced nephron number and reduced glomerular filtration rate. Time-courses for each model were derived for acute kidney injury scenarios of structural damage and/or reduced nephron number. The model predicted that pre-formed biomarkers would respond quickest to injury with a brief period of elevation, which would be easily missed in clinical scenarios. Induced biomarker time-courses would be influenced by biomarker-specific physiology and the balance between insult severity (which increased single nephron excretion), the number of remaining nephrons (reduced total excretion), and the extent of glomerular filtration rate reduction (increased concentration). Filtered biomarkers have the longest time-course because plasma levels increased following glomerular filtration rate decrease. Peak concentration and profile depended on the extent of damage to the reabsorption mechanism and recovery rate. Rapid recovery may be detected through a rapid reduction in urinary concentration. For all biomarkers, impaired hyperfiltration substantially increased concentration, especially with chronic kidney disease. For clinical validation of these model-derived predictions the clinical biomarker of choice will depend on timing in relation to renal insult and interpretation will require the pre-insult nephron number (renal mass) and detection of hyperfiltration. Public Library of Science 2014-07-09 /pmc/articles/PMC4090122/ /pubmed/25006799 http://dx.doi.org/10.1371/journal.pone.0101288 Text en © 2014 Pickering, Endre http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Pickering, John W. Endre, Zoltán H. Acute Kidney Injury Urinary Biomarker Time-Courses |
title | Acute Kidney Injury Urinary Biomarker Time-Courses |
title_full | Acute Kidney Injury Urinary Biomarker Time-Courses |
title_fullStr | Acute Kidney Injury Urinary Biomarker Time-Courses |
title_full_unstemmed | Acute Kidney Injury Urinary Biomarker Time-Courses |
title_short | Acute Kidney Injury Urinary Biomarker Time-Courses |
title_sort | acute kidney injury urinary biomarker time-courses |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090122/ https://www.ncbi.nlm.nih.gov/pubmed/25006799 http://dx.doi.org/10.1371/journal.pone.0101288 |
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