Intestinal alkaline phosphatase modulation by food components: predictive, preventive, and personalized strategies for novel treatment options in chronic kidney disease

Abstract

Alkaline phosphatase (AP) is a ubiquitous membrane–bound glycoprotein that catalyzes phosphate monoesters’ hydrolysis from organic compounds, an essential process in cell signaling. Four AP isozymes have been described in humans, placental AP, germ cell AP, tissue nonspecific AP, and intestinal AP (IAP). IAP plays a crucial role in gut microbial homeostasis, nutrient uptake, and local and systemic inflammation, and its dysfunction is associated with persistent inflammatory disorders. AP is a strong predictor of mortality in the general population and patients with cardiovascular and chronic kidney disease (CKD). However, little is known about IAP modulation and its possible consequences in CKD, a disease characterized by gut microbiota imbalance and persistent low-grade inflammation. Mitigating inflammation and dysbiosis can prevent cardiovascular complications in patients with CKD, and monitoring factors such as IAP can be useful for predicting those complications. Here, we review IAP’s role and the results of nutritional interventions targeting IAP in experimental models to prevent alterations in the gut microbiota, which could be a possible target of predictive, preventive, personalized medicine (PPPM) to avoid CKD complications. Microbiota and some nutrients may activate IAP, which seems to have a beneficial impact on health; however, data on CKD remains scarce.

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Funding

Conselho Nacional de Pesquisa (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) support Denise Mafra research. The Heart and Lung Foundation, CIMED and “Njurfonden” support Peter Stenvinkel’s research. Baxter Novum is the result of a grant from Baxter Healthcare to Karolinska Institutet. Bengt Lindholm is affiliated with Baxter Healthcare.

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Alvarenga, L., Cardozo, L.F.M.F., Lindholm, B. et al. Intestinal alkaline phosphatase modulation by food components: predictive, preventive, and personalized strategies for novel treatment options in chronic kidney disease. EPMA Journal 11, 565–579 (2020). https://doi.org/10.1007/s13167-020-00228-9

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Keywords

  • Intestinal alkaline phosphatase
  • Chronic kidney disease
  • Inflammation
  • Gut microbiota
  • Predictive diagnosis
  • Predictive preventive personalized medicine (PPPM/3 PM)