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Alkaline Phosphatases in the Complex Chronic Kidney Disease-Mineral and Bone Disorders

Calcified Tissue International volume 103, pages 111–124 (2018)Cite this article

Abstract

Alkaline phosphatases (APs) remove the phosphate (dephosphorylation) needed in multiple metabolic processes (from many molecules such as proteins, nucleotides, or pyrophosphate). Therefore, APs are important for bone mineralization but paradoxically they can also be deleterious for other processes, such as vascular calcification and the increasingly known cross-talk between bone and vessels. A proper balance between beneficial and harmful activities is further complicated in the context of chronic kidney disease (CKD). In this narrative review, we will briefly update the complexity of the enzyme, including its different isoforms such as the bone-specific alkaline phosphatase or the most recently discovered B1x. We will also analyze the correlations and potential discrepancies with parathyroid hormone and bone turnover and, most importantly, the valuable recent associations of AP’s with cardiovascular disease and/or vascular calcification, and survival. Finally, a basic knowledge of the synthetic and degradation pathways of APs promises to open new therapeutic strategies for the treatment of the CKD-Mineral and Bone Disorder (CKD-MBD) in the near future, as well as for other processes such as sepsis, acute kidney injury, inflammation, endothelial dysfunction, metabolic syndrome or, in diabetes, cardiovascular complications. However, no studies have been done using APs as a primary therapeutic target for clinical outcomes, and therefore, AP’s levels cannot yet be used alone as an isolated primary target in the treatment of CKD-MBD. Nonetheless, its diagnostic and prognostic potential should be underlined.

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Acknowledgements

Dr Jordi Bover belongs to the Spanish National Network of Kidney Research RedinRen (RD06/0016/0001 and RD12/0021/0033) and the Spanish National Biobank network RD09/0076/00064. Dr Jordi Bover also belongs to the Catalan Nephrology Research Group AGAUR 2009 SGR-1116 and collaborates with the Spanish Fundación Iñigo Alvarez de Toledo (FRIAT). We thank Mr. Ricardo Pellejero for his invaluable bibliographic assistance.

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Authors and Affiliations

  1. Department of Nephrology, Fundació Puigvert, IIB Sant Pau, RedinRen, C. Cartagena, Catalonia, 340-350, Barcelona, Spain

    Jordi Bover, Armando Aguilar, Silvia Benito, Víctor López-Báez, Alejandra Ramos & Iara daSilva

  2. Department of Nephrology and Dialysis, Clinique du Landy and Department of Renal Physiology, Necker Hospital, University of Paris Descartes, Paris, France

    Pablo Ureña

  3. Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy

    Sandro Mazzaferro

  4. Laboratory of Experimental Nephrology, Renal Division,San Paolo Hospital, DiSS University of Milan, Milan, Italy

    Mario Cozzolino

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Bover, J., Ureña, P., Aguilar, A. et al. Alkaline Phosphatases in the Complex Chronic Kidney Disease-Mineral and Bone Disorders. Calcif Tissue Int 103, 111–124 (2018). https://doi.org/10.1007/s00223-018-0399-z

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  • DOI: https://doi.org/10.1007/s00223-018-0399-z

Keywords

  • Alkaline phosphatase
  • Bone alkaline phosphatase
  • CKD
  • CKD-MBD
  • Pyrophosphate
  • Vascular calcification
  • Survival