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Multimarker Panels in Diabetic Kidney Disease: The Way to Improved Clinical Trial Design and Clinical Practice?

Diabetic kidney disease (DKD) is a complex and multifactorial disorder associated with deregulations in a large number of different biological pathways on the molecular level. Using the 2 established biomarkers, estimated glomerular filtration rate (eGFR) and albuminuria will not allow allocating pa...

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Detalles Bibliográficos
Autores principales: Perco, Paul, Pena, Michelle, Heerspink, Hiddo J.L., Mayer, Gert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365367/
https://www.ncbi.nlm.nih.gov/pubmed/30775618
http://dx.doi.org/10.1016/j.ekir.2018.12.001
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author Perco, Paul
Pena, Michelle
Heerspink, Hiddo J.L.
Mayer, Gert
author_facet Perco, Paul
Pena, Michelle
Heerspink, Hiddo J.L.
Mayer, Gert
author_sort Perco, Paul
collection PubMed
description Diabetic kidney disease (DKD) is a complex and multifactorial disorder associated with deregulations in a large number of different biological pathways on the molecular level. Using the 2 established biomarkers, estimated glomerular filtration rate (eGFR) and albuminuria will not allow allocating patients to tailored therapy. Molecular multimarker panels as sensors for the deregulation of the various disease mechanisms combined with a better understanding of how investigational as well as approved drugs interfere with these disease processes forms the basis for platform trials in DKD. In these platform trials, patients with DKD are assigned to the most suitable treatment arm based on their molecular marker profile. Close monitoring of biomarkers after treatment initiation together with assessment of renal function and “off-target” effects will allow identification of therapy responders, with nonresponders shifted to the next-best treatment arm based on their molecular profile. In this viewpoint article, we summarize evidence on the variation of DKD disease progression as well as the response to therapy and outline procedures to model disease pathophysiology supporting biomarker panel construction. Finally, the use of biomarkers in clinical trial setup is discussed.
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spelling pubmed-63653672019-02-15 Multimarker Panels in Diabetic Kidney Disease: The Way to Improved Clinical Trial Design and Clinical Practice? Perco, Paul Pena, Michelle Heerspink, Hiddo J.L. Mayer, Gert Kidney Int Rep Review Diabetic kidney disease (DKD) is a complex and multifactorial disorder associated with deregulations in a large number of different biological pathways on the molecular level. Using the 2 established biomarkers, estimated glomerular filtration rate (eGFR) and albuminuria will not allow allocating patients to tailored therapy. Molecular multimarker panels as sensors for the deregulation of the various disease mechanisms combined with a better understanding of how investigational as well as approved drugs interfere with these disease processes forms the basis for platform trials in DKD. In these platform trials, patients with DKD are assigned to the most suitable treatment arm based on their molecular marker profile. Close monitoring of biomarkers after treatment initiation together with assessment of renal function and “off-target” effects will allow identification of therapy responders, with nonresponders shifted to the next-best treatment arm based on their molecular profile. In this viewpoint article, we summarize evidence on the variation of DKD disease progression as well as the response to therapy and outline procedures to model disease pathophysiology supporting biomarker panel construction. Finally, the use of biomarkers in clinical trial setup is discussed. Elsevier 2018-12-18 /pmc/articles/PMC6365367/ /pubmed/30775618 http://dx.doi.org/10.1016/j.ekir.2018.12.001 Text en © 2018 International Society of Nephrology. Published by Elsevier Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Perco, Paul
Pena, Michelle
Heerspink, Hiddo J.L.
Mayer, Gert
Multimarker Panels in Diabetic Kidney Disease: The Way to Improved Clinical Trial Design and Clinical Practice?
title Multimarker Panels in Diabetic Kidney Disease: The Way to Improved Clinical Trial Design and Clinical Practice?
title_full Multimarker Panels in Diabetic Kidney Disease: The Way to Improved Clinical Trial Design and Clinical Practice?
title_fullStr Multimarker Panels in Diabetic Kidney Disease: The Way to Improved Clinical Trial Design and Clinical Practice?
title_full_unstemmed Multimarker Panels in Diabetic Kidney Disease: The Way to Improved Clinical Trial Design and Clinical Practice?
title_short Multimarker Panels in Diabetic Kidney Disease: The Way to Improved Clinical Trial Design and Clinical Practice?
title_sort multimarker panels in diabetic kidney disease: the way to improved clinical trial design and clinical practice?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365367/
https://www.ncbi.nlm.nih.gov/pubmed/30775618
http://dx.doi.org/10.1016/j.ekir.2018.12.001
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