{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:24:55Z","timestamp":1791944695715,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,23]],"date-time":"2019-11-23T00:00:00Z","timestamp":1574467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Medial arterial calcification (MAC) is a major complication of chronic kidney disease (CKD) and an indicator of poor prognosis. Aortic overexpression of tissue\u2010nonspecific alkaline phosphatase (TNAP) accelerates MAC formation. The present study aimed to assess whether a TNAP inhibitor, SBI\u2010425, protects against MAC and improves survival probability in a CKD\u2010mineral and bone disorder (MBD) mouse model. CKD\u2010MBD mice were divided in three groups: vehicle, SBI\u201010, and SBI\u201030. They were fed a 0.2% adenine and 0.8% phosphorus diet from 14 to 20\u2009weeks of age to induce CKD, followed by a high\u2010phosphorus (0.2% adenine and 1.8% phosphorus) diet for another 6\u2009weeks. At 14\u201320\u2009weeks of age, mice in the SBI\u201010 and SBI\u201030 groups were given 10 and 30\u2009mg\/kg SBI\u2010425 by gavage once a day, respectively, while vehicle\u2010group mice were given distilled water as vehicle. Control mice were fed a standard chow (0.8% phosphorus) between the ages of 8 and 20\u2009weeks. Computed tomography imaging, histology, and aortic tissue calcium content revealed that, compared to vehicle animals, SBI\u2010425 nearly halted the formation of MAC. Mice in the control, SBI\u201010 and SBI\u201030 groups exhibited 100% survival, which was significantly better than vehicle\u2010treated mice (57.1%). Aortic mRNA expression of <jats:italic>Alpl<\/jats:italic>, encoding TNAP, as well as plasma and aortic tissue TNAP activity, were suppressed by SBI\u2010425 administration, whereas plasma pyrophosphate increased. We conclude that a TNAP inhibitor successfully protected the vasculature from MAC and improved survival rate in a mouse CKD\u2010MBD model, without causing any adverse effects on normal skeletal formation and residual renal function. \u00a9 2019 Pathological Society of Great Britain and Ireland. 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