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Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease

Alkaline phosphatase (ALP) is an evolutionary conserved enzyme and widely used biomarker in clinical practice. Tissue-nonspecific alkaline phosphatase (TNALP) is one of four human isozymes that are expressed as distinct TNALP isoforms after posttranslational modifications, mainly in bone, liver, and...

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Autores principales: Haarhaus, Mathias, Cianciolo, Giuseppe, Barbuto, Simona, La Manna, Gaetano, Gasperoni, Lorenzo, Tripepi, Giovanni, Plebani, Mario, Fusaro, Maria, Magnusson, Per
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144546/
https://www.ncbi.nlm.nih.gov/pubmed/35631265
http://dx.doi.org/10.3390/nu14102124
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author Haarhaus, Mathias
Cianciolo, Giuseppe
Barbuto, Simona
La Manna, Gaetano
Gasperoni, Lorenzo
Tripepi, Giovanni
Plebani, Mario
Fusaro, Maria
Magnusson, Per
author_facet Haarhaus, Mathias
Cianciolo, Giuseppe
Barbuto, Simona
La Manna, Gaetano
Gasperoni, Lorenzo
Tripepi, Giovanni
Plebani, Mario
Fusaro, Maria
Magnusson, Per
author_sort Haarhaus, Mathias
collection PubMed
description Alkaline phosphatase (ALP) is an evolutionary conserved enzyme and widely used biomarker in clinical practice. Tissue-nonspecific alkaline phosphatase (TNALP) is one of four human isozymes that are expressed as distinct TNALP isoforms after posttranslational modifications, mainly in bone, liver, and kidney tissues. Beyond the well-known effects on bone mineralization, the bone ALP (BALP) isoforms (B/I, B1, B1x, and B2) are also involved in the pathogenesis of ectopic calcification. This narrative review summarizes the recent clinical investigations and mechanisms that link ALP and BALP to inflammation, metabolic syndrome, vascular calcification, endothelial dysfunction, fibrosis, cardiovascular disease, and mortality. The association between ALP, vitamin K, bone metabolism, and fracture risk in patients with chronic kidney disease (CKD) is also discussed. Recent advances in different pharmacological strategies are highlighted, with the potential to modulate the expression of ALP directly and indirectly in CKD–mineral and bone disorder (CKD-MBD), e.g., epigenetic modulation, phosphate binders, calcimimetics, vitamin D, and other anti-fracture treatments. We conclude that the significant evidence for ALP as a pathogenic factor and risk marker in CKD-MBD supports the inclusion of concrete treatment targets for ALP in clinical guidelines. While a target value below 120 U/L is associated with improved survival, further experimental and clinical research should explore interventional strategies with optimal risk–benefit profiles. The future holds great promise for novel drug therapies modulating ALP.
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spelling pubmed-91445462022-05-29 Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease Haarhaus, Mathias Cianciolo, Giuseppe Barbuto, Simona La Manna, Gaetano Gasperoni, Lorenzo Tripepi, Giovanni Plebani, Mario Fusaro, Maria Magnusson, Per Nutrients Review Alkaline phosphatase (ALP) is an evolutionary conserved enzyme and widely used biomarker in clinical practice. Tissue-nonspecific alkaline phosphatase (TNALP) is one of four human isozymes that are expressed as distinct TNALP isoforms after posttranslational modifications, mainly in bone, liver, and kidney tissues. Beyond the well-known effects on bone mineralization, the bone ALP (BALP) isoforms (B/I, B1, B1x, and B2) are also involved in the pathogenesis of ectopic calcification. This narrative review summarizes the recent clinical investigations and mechanisms that link ALP and BALP to inflammation, metabolic syndrome, vascular calcification, endothelial dysfunction, fibrosis, cardiovascular disease, and mortality. The association between ALP, vitamin K, bone metabolism, and fracture risk in patients with chronic kidney disease (CKD) is also discussed. Recent advances in different pharmacological strategies are highlighted, with the potential to modulate the expression of ALP directly and indirectly in CKD–mineral and bone disorder (CKD-MBD), e.g., epigenetic modulation, phosphate binders, calcimimetics, vitamin D, and other anti-fracture treatments. We conclude that the significant evidence for ALP as a pathogenic factor and risk marker in CKD-MBD supports the inclusion of concrete treatment targets for ALP in clinical guidelines. While a target value below 120 U/L is associated with improved survival, further experimental and clinical research should explore interventional strategies with optimal risk–benefit profiles. The future holds great promise for novel drug therapies modulating ALP. MDPI 2022-05-19 /pmc/articles/PMC9144546/ /pubmed/35631265 http://dx.doi.org/10.3390/nu14102124 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Haarhaus, Mathias
Cianciolo, Giuseppe
Barbuto, Simona
La Manna, Gaetano
Gasperoni, Lorenzo
Tripepi, Giovanni
Plebani, Mario
Fusaro, Maria
Magnusson, Per
Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease
title Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease
title_full Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease
title_fullStr Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease
title_full_unstemmed Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease
title_short Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease
title_sort alkaline phosphatase: an old friend as treatment target for cardiovascular and mineral bone disorders in chronic kidney disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144546/
https://www.ncbi.nlm.nih.gov/pubmed/35631265
http://dx.doi.org/10.3390/nu14102124
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