2. Academic Validation
  3. Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD

Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD

  • Nat Rev Nephrol. 2017 Jul;13(7):429-442. doi: 10.1038/nrneph.2017.60.
Mathias Haarhaus 1 2,  Vincent Brandenburg 3,  Kamyar Kalantar-Zadeh 4 5,  Peter Stenvinkel 1,  Per Magnusson 2
Affiliations

Affiliations

  • 1 Division of Renal Medicine and Baxter Novum, Karolinska Institutet, Karolinska University Hospital, SE-14186 Stockholm, Sweden.
  • 2 Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, SE-58185 Linköping, Sweden.
  • 3 Department of Cardiology and Intensive Care Medicine, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen, Germany.
  • 4 Harold Simmons Center for Kidney Disease Research and Epidemiology and Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, 101 The City Drive South, City Tower, Suite 400, Mail Code: 4088, Orange, California 92868, USA.
  • 5 Department of Epidemiology, UCLA Fielding School of Public Health, 1124 West Carson Street Suite C-1 Annex, Torrance, California 90502, USA.
PMID: 28502983 DOI: 10.1038/nrneph.2017.60
Abstract

Cardiovascular Disease is the main cause of early death in the settings of chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and ageing. Cardiovascular events can be caused by an imbalance between promoters and inhibitors of mineralization, which leads to vascular calcification. This process is akin to skeletal mineralization, which is carefully regulated and in which isozymes of Alkaline Phosphatase (ALP) have a crucial role. Four genes encode ALP isozymes in humans. Intestinal, placental and germ cell ALPs are tissue-specific, whereas the tissue-nonspecific isozyme of ALP (TNALP) is present in several tissues, including bone, liver and kidney. TNALP has a pivotal role in bone calcification. Experimental overexpression of TNALP in the vasculature is sufficient to induce vascular calcification, cardiac hypertrophy and premature death, mimicking the cardiovascular phenotype often found in CKD and T2DM. Intestinal ALP contributes to the gut mucosal defence and intestinal and liver ALPs might contribute to the acute inflammatory response to endogenous or pathogenic stimuli. Here we review novel mechanisms that link ALP to vascular calcification, inflammation, and endothelial dysfunction in kidney and cardiovascular diseases. We also discuss new drugs that target ALP, which have the potential to improve cardiovascular outcomes without inhibiting skeletal mineralization.

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