{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T17:26:26Z","timestamp":1794072386187,"version":"4.8.0"},"reference-count":189,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Region \u00d6sterg\u00f6tland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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\u2013mineral 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\u2013benefit profiles. The future holds great promise for novel drug therapies modulating ALP.<\/jats:p>","DOI":"10.3390\/nu14102124","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:18:11Z","timestamp":1653005891000},"page":"2124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":125,"title":["Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8274-6356","authenticated-orcid":false,"given":"Mathias","family":"Haarhaus","sequence":"first","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, SE-14186 Stockholm, Sweden"},{"name":"Diaverum Sweden AB, SE-21537 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Cianciolo","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Renal Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2303-7845","authenticated-orcid":false,"given":"Simona","family":"Barbuto","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Renal Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"La Manna","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Renal Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gasperoni","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, AUSL Romagna Infermi Hospital, 47923 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Tripepi","sequence":"additional","affiliation":[{"name":"CNR-IFC, Clinical Epidemiology of Renal Diseases and Hypertension, Ospedali Riuniti, 89124 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0270-1711","authenticated-orcid":false,"given":"Mario","family":"Plebani","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Unit, Department of Medicine, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9478-4851","authenticated-orcid":false,"given":"Maria","family":"Fusaro","sequence":"additional","affiliation":[{"name":"National Research Council (CNR), Institute of Clinical Physiology (IFC), Via G. Moruzzi 1, 56124 Pisa, Italy"},{"name":"Department of Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2123-7838","authenticated-orcid":false,"given":"Per","family":"Magnusson","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, and Department of Biomedical and Clinical Sciences, Link\u00f6ping University, SE-58185 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s11302-005-5435-6","article-title":"Alkaline Phosphatases","volume":"2","year":"2006","journal-title":"Purinergic Signal."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1469-1809.1986.tb01043.x","article-title":"Mapping of the Gene Coding for the Human Liver\/Bone\/Kidney Isozyme of Alkaline Phosphatase to Chromosome 1","volume":"50","author":"Swallow","year":"1986","journal-title":"Ann. 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