Skip to main content

Advertisement

SpringerLink
Log in

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

  • Review
  • Published:
EPMA Journal Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Haarhaus M, Brandenburg V, Kalantar-Zadeh K, Stenvinkel P, Magnusson P. Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD. Nat Rev Nephrol. 2017;13(7):429–42. https://doi.org/10.1038/nrneph.2017.60.

    Article  CAS  PubMed  Google Scholar 

  2. Buchet R, Millán JL, Magne D. Multisystemic functions of alkaline phosphatases. Methods Mol Biol. 2013;1053:27–51. https://doi.org/10.1007/978-1-62703-562-0_3.

    Article  CAS  PubMed  Google Scholar 

  3. Ghosh SS, Wang J, Yannie PJ, Ghosh S. Intestinal barrier dysfunction, LPS translocation, and disease development. J Endocr Soc. 2020;4(2):bvz039. https://doi.org/10.1210/jendso/bvz039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Parlato M, Charbit-Henrion F, Pan J, Romano C, Duclaux-Loras R, Le Du MH, et al. Human ALPI deficiency causes inflammatory bowel disease and highlights a key mechanism of gut homeostasis. EMBO Mol Med. 2018;10(4):e8483. https://doi.org/10.15252/emmm.201708483.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bilski J, Mazur-Bialy A, Wojcik D, Surmiak M, Magierowski M, Sliwowski Z, et al. Role of obesity, mesenteric adipose tissue, and adipokines in inflammatory bowel diseases. Biomolecules. 2019;9(12):780. https://doi.org/10.3390/biom9120780.

    Article  CAS  PubMed Central  Google Scholar 

  6. Dai L, Golembiewska E, Lindholm B, Stenvinkel P. End-stage renal disease, inflammation and cardiovascular outcomes. Contrib Nephrol. 2017;191:32–43. https://doi.org/10.1159/000479254.

    Article  CAS  PubMed  Google Scholar 

  7. Lundquist AL, Nigwekar SU. Optimal management of bone mineral disorders in chronic kidney disease and end stage renal disease. Curr Opin Nephrol Hypertens. 2016;25(2):120–6. https://doi.org/10.1097/MNH.0000000000000203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nizet A, Cavalier E, Stenvinkel P, Haarhaus M, Magnusson P. Bone alkaline phosphatase: an important biomarker in chronic kidney disease - mineral and bone disorder. Clin Chim Acta. 2020;501:198–206. https://doi.org/10.1016/j.cca.2019.11.012.

    Article  CAS  PubMed  Google Scholar 

  9. Vervloet MG, Brandenburg VM, CKD-MBD working group of ERA-EDTA, et al. J Nephrol. 2017;30(5):663–70. https://doi.org/10.1007/s40620-017-0408-8.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Chen Z, Zhang X, Han F, Xie X, Hua Z, Huang X, et al. High alkaline phosphatase and low intact parathyroid hormone associate with worse clinical outcome in peritoneal dialysis patients. Perit Dial Int. 2020;4:896860820918131. https://doi.org/10.1177/0896860820918131.

    Article  Google Scholar 

  11. Fan Y, Jin X, Jiang M, Fang N. Elevated serum alkaline phosphatase and cardiovascular or all-cause mortality risk in dialysis patients: a meta-analysis. Sci Rep. 2017;7(1):13224. https://doi.org/10.1038/s41598-017-13387-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sumida K, Molnar MZ, Potukuchi PK, Thomas F, Lu JL, Obi Y, et al. Prognostic significance of pre-end-stage renal disease serum alkaline phosphatase for post-end-stage renal disease mortality in late-stage chronic kidney disease patients transitioning to dialysis. Nephrol Dial Transplant. 2018;33(2):264–73. https://doi.org/10.1093/ndt/gfw412.

    Article  CAS  PubMed  Google Scholar 

  13. Fawley J, Gourlay DM. Intestinal alkaline phosphatase: a summary of its role in clinical disease. J Surg Res. 2016;202(1):225–34. https://doi.org/10.1016/j.jss.2015.12.008.

    Article  CAS  PubMed  Google Scholar 

  14. Qian S, Golubnitschaja O, Zhan X. Chronic inflammation: key player and biomarker-set to predict and prevent cancer development and progression based on individualized patient profiles. EPMA J. 2019 Nov 20;10(4):365–81.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Maturo MG, Soligo M, Gibson G, Manni L, Nardini C. The greater inflammatory pathway-high clinical potential by innovative predictive, preventive, and personalized medical approach. EPMA J. 2019;11(1):1–16. https://doi.org/10.1007/s13167-019-00195-w.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Stockler-Pinto MB, Soulage CO, Borges NA, Cardozo LFMF, Dolenga CJ, Nakao LS, et al. From bench to the hemodialysis clinic: protein-bound uremic toxins modulate NF-κB/Nrf2 expression. Int Urol Nephrol. 2018;50(2):347–54. https://doi.org/10.1007/s11255-017-1748-y.

    Article  CAS  PubMed  Google Scholar 

  17. Borges NA, Barros AF, Nakao LS, Dolenga CJ, Fouque D, Mafra D. Protein-bound uremic toxins from gut microbiota and inflammatory markers in chronic kidney disease. J Ren Nutr. 2016;26(6):396–400. https://doi.org/10.1053/j.jrn.2016.07.005.

    Article  CAS  PubMed  Google Scholar 

  18. Kunin A, Polivka J Jr, Moiseeva N, Golubnitschaja O. “Dry mouth” and “Flammer” syndromes-neglected risks in adolescents and new concepts by predictive, preventive and personalised approach. EPMA J. 2018;9(3):307–17. https://doi.org/10.1007/s13167-018-0145-7.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Thoppay J, Desai B. Oral burning: local and systemic connection for a patient-centric approach. EPMA J. 2019;10(1):1–11. https://doi.org/10.1007/s13167-018-0157-3.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Goncharenko V, Bubnov R, Polivka J Jr, Zubor P, Biringer K, Bielik T, et al. Vaginal dryness: individualised patient profiles, risks and mitigating measures. EPMA J. 2019;10(1):73–9. https://doi.org/10.1007/s13167-019-00164-3.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Golubnitschaja O, Kinkorova J, Costigliola V. Predictive, preventive and personalised medicine as the hardcore of ‘Horizon 2020’: EPMA position paper. EPMA J. 2014;5(1):6. https://doi.org/10.1186/1878-5085-5-6.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Golubnitschaja O, Baban B, Boniolo G, Wang W, Bubnov R, Kapalla M, et al. Medicine in the early twenty-first century: paradigm and anticipation - EPMA position paper 2016. EPMA J. 2016;7(1):23. https://doi.org/10.1186/s13167-016-0072-4.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Millán JL. Alkaline phosphatases: structure, substrate specificity and functional relatedness to other members of a large superfamily of enzymes. Purinergic Signal. 2006;2(2):335–41. https://doi.org/10.1007/s11302-005-5435-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hoylaerts MF, Manes T, Millán JL. Mammalian alkaline phosphatases are allosteric enzymes. J Biol Chem. 1997;272(36):22781–7. https://doi.org/10.1074/jbc.272.36.22781.

    Article  CAS  PubMed  Google Scholar 

  25. Rader BA. Alkaline phosphatase, an unconventional immune protein. Front Immunol. 2017;8:897. https://doi.org/10.3389/fimmu.2017.00897.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hirschmugl B, Crozier S, Matthews N, Kitzinger E, Klymiuk I, Inskip HM, et al. Relation of placental alkaline phosphatase expression in human term placenta with maternal and offspring fat mass. Int J Obes. 2018;42(6):1202–10. https://doi.org/10.1038/s41366-018-0136-8.

    Article  CAS  Google Scholar 

  27. Haarhaus M, Gilham D, Kulikowski E, Magnusson P, Kalantar-Zadeh K. Pharmacologic epigenetic modulators of alkaline phosphatase in chronic kidney disease. Curr Opin Nephrol Hypertens. 2020;29(1):4–15. https://doi.org/10.1097/MNH.0000000000000570.

    Article  CAS  PubMed  Google Scholar 

  28. Lynes M, Narisawa S, Millán JL, Widmaier EP. Interactions between CD36 and global intestinal alkaline phosphatase in mouse small intestine and effects of high-fat diet. Am J Phys Regul Integr Comp Phys. 2011;301(6):R1738–47. https://doi.org/10.1152/ajpregu.00235.2011.

    Article  CAS  Google Scholar 

  29. Young GP, Friedman S, Yedlin ST, Allers DH. Effect of fat feeding on intestinal alkaline phosphatase activity in tissue and serum. Am J Phys. 1981;241(6):G461–8. https://doi.org/10.1152/ajpgi.1981.241.6.G461.

    Article  CAS  Google Scholar 

  30. Chen KT, Malo MS, Moss AK, Zeller S, Johnson P, Ebrahimi F, et al. Identification of specific targets for the gut mucosal defense factor intestinal alkaline phosphatase. Am J Physiol Gastrointest Liver Physiol. 2010;299(2):G467–75. https://doi.org/10.1152/ajpgi.00364.2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Narisawa S, Hoylaerts MF, Doctor KS, Fukuda MN, Alpers DH, Millán JL. A novel phosphatase upregulated in Akp3 knockout mice. Am J Physiol Gastrointest Liver Physiol. 2007;293(5):G1068–77. https://doi.org/10.1152/ajpgi.00073.2007.

    Article  CAS  PubMed  Google Scholar 

  32. Lallès JP. Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet. Nutr Rev. 2010;68(6):323–32. https://doi.org/10.1111/j.1753-4887.2010.00292.x.

    Article  PubMed  Google Scholar 

  33. Lallès JP. Recent advances in intestinal alkaline phosphatase, inflammation, and nutrition. Nutr Rev. 2019;77(10):710–24. https://doi.org/10.1093/nutrit/nuz015.

    Article  PubMed  Google Scholar 

  34. Lallès JP. Luminal ATP: the missing link between intestinal alkaline phosphatase, the gut microbiota, and inflammation? Am J Physiol Gastrointest Liver Physiol. 2014a;306(10):G824–5. https://doi.org/10.1152/ajpgi.00435.2013.

    Article  CAS  PubMed  Google Scholar 

  35. Lassenius MI, Fogarty CL, Blaut M, Haimila K, Riittinen L, Paju A, et al. Intestinal alkaline phosphatase at the crossroad of intestinal health and disease - a putative role in type 1 diabetes. J Intern Med. 2017;281(6):586–600. https://doi.org/10.1111/joim.12607.

    Article  CAS  PubMed  Google Scholar 

  36. Tsumura M, Ueno Y, Kinouchi T, Koyama I, Komoda T. Atypical alkaline phosphatase isozymes in serum and urine of patients with renal failure. Clin Chim Acta. 2001;312(1–2):169–78. https://doi.org/10.1016/s0009-8981(01)00606-4.

    Article  CAS  PubMed  Google Scholar 

  37. Zetterberg H. Increased serum concentrations of intestinal alkaline phosphatase in peritoneal dialysis. Clin Chem. 2005;51(3):675–6. https://doi.org/10.1373/clinchem.2004.045831.

    Article  CAS  PubMed  Google Scholar 

  38. Liu W, Hu D, Huo H, Zhang W, Adiliaghdam F, Morrison S, et al. Intestinal alkaline phosphatase regulates tight junction protein levels. J Am Coll Surg. 2016;222(6):1009–17. https://doi.org/10.1016/j.jamcollsurg.2015.12.006.

    Article  PubMed  Google Scholar 

  39. Brzozowski B, Mazur-Bialy A, Pajdo R, Kwiecien S, Bilski J, Zwolinska-Wcislo M, et al. Mechanisms by which stress affects the experimental and clinical inflammatory bowel disease (IBD): role of brain-gut axis. Curr Neuropharmacol. 2016;14(8):892–900. https://doi.org/10.2174/1570159x14666160404124127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Komazin G, Maybin M, Woodard RW, Scior T, Schwudke D, Schombel U, et al. Substrate structure-activity relationship reveals a limited lipopolysaccharide chemotype range for intestinal alkaline phosphatase. J Biol Chem. 2019;294(50):19405–23. https://doi.org/10.1074/jbc.RA119.010836.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lallès JP. Intestinal alkaline phosphatase: novel functions and protective effects. Nutr Rev. 2014b;72(2):82–94. https://doi.org/10.1111/nure.12082.

    Article  PubMed  Google Scholar 

  42. Malo MS, Moaven O, Muhammad N, Biswas B, Alam SN, Economopoulos KP, et al. Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the concentration of luminal nucleotide triphosphates. Am J Physiol Gastrointest Liver Physiol. 2014;306(10):G826–38. https://doi.org/10.1152/ajpgi.00357.2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Bilski J, Mazur-Bialy A, Wojcik D, Zahradnik-Bilska J, Brzozowski B, Magierowski M, et al. The role of intestinal alkaline phosphatase in inflammatory disorders of gastrointestinal tract. Mediat Inflamm. 2017;2017:9074601. https://doi.org/10.1155/2017/9074601.

    Article  CAS  Google Scholar 

  44. Bentala H, Verweij WR, Huizinga-Van der Vlag A, van Loenen-Weemaes AM, Meijer DK, Poelstra K. Removal of phosphate from lipid A as a strategy to detoxify lipopolysaccharide. Shock. 2002;18(6):561–6. https://doi.org/10.1097/00024382-200212000-00013.

    Article  PubMed  Google Scholar 

  45. Peters E, Geraci S, Heemskerk S, Wilmer MJ, Bilos A, Kraenzlin B, et al. Alkaline phosphatase protects against renal inflammation through dephosphorylation of lipopolysaccharide and adenosine triphosphate. Br J Pharmacol. 2015;172(20):4932–45. https://doi.org/10.1111/bph.13261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Tuin A, Poelstra K, de Jager-Krikken A, Bok L, Raaben W, Velders MP, et al. Role of alkaline phosphatase in colitis in man and rats. Gut. 2009;58(3):379–87. https://doi.org/10.1136/gut.2007.128868.

    Article  CAS  PubMed  Google Scholar 

  47. Molnár K, Vannay A, Szebeni B, Bánki NF, Sziksz E, Cseh A, et al. Intestinal alkaline phosphatase in the colonic mucosa of children with inflammatory bowel disease. World J Gastroenterol. 2012;18(25):3254–9. https://doi.org/10.3748/wjg.v18.i25.3254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Malo J, Alam MJ, Shahnaz M, Kaliannan K, Chandra G, Aziz T, et al. Intestinal alkaline phosphatase deficiency is associated with ischemic heart disease. Dis Markers. 2019;2019:8473565–11. https://doi.org/10.1155/2019/8473565.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Malo MS. A high level of intestinal alkaline phosphatase is protective against type 2 diabetes mellitus irrespective of obesity. EBioMedicine. 2015;2(12):2016–23. https://doi.org/10.1016/j.ebiom.2015.11.027.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Janssens S, Beyaert R. Role of toll-like receptors in pathogen recognition. Clin Microbiol Rev. 2003;16(4):637–46. https://doi.org/10.1128/cmr.16.4.637-646.2003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Goldberg RF, Austen WG Jr, Zhang X, Munene G, Mostafa G, Biswas S, et al. Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proc Natl Acad Sci U S A. 2008;105(9):3551–6. https://doi.org/10.1073/pnas.0712140105.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Lallès JP. Microbiota-host interplay at the gut epithelial level, health and nutrition. J Anim Sci Biotechnol. 2016;7:66. https://doi.org/10.1186/s40104-016-0123-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Hwang SW, Kim JH, Lee C, Im JP, Kim JS. Intestinal alkaline phosphatase ameliorates experimental colitis via toll-like receptor 4-dependent pathway. Eur J Pharmacol. 2018;820:156–66. https://doi.org/10.1016/j.ejphar.2017.12.026.

    Article  CAS  PubMed  Google Scholar 

  54. Bates JM, Mittge E, Kuhlman J, Baden KN, Cheesman SE, Guillemin K. Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation. Dev Biol. 2006;297(2):374–86. https://doi.org/10.1016/j.ydbio.2006.05.006.

    Article  CAS  PubMed  Google Scholar 

  55. Fawley J, Koehler S, Cabrera S, Lam V, Fredrich K, Hessner M, et al. Intestinal alkaline phosphatase deficiency leads to dysbiosis and bacterial translocation in the newborn intestine. J Surg Res. 2017;218:35–42. https://doi.org/10.1016/j.jss.2017.03.049.

    Article  CAS  PubMed  Google Scholar 

  56. Malo MS, Alam SN, Mostafa G, Zeller SJ, Johnson PV, Mohammad N, et al. Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota. Gut. 2010;59(11):1476–84. https://doi.org/10.1136/gut.2010.211706.

    Article  CAS  PubMed  Google Scholar 

  57. Singh SB, Carroll-Portillo A, Coffman C, Ritz NL, Lin HC. Intestinal alkaline phosphatase exerts anti-inflammatory effects against lipopolysaccharide by inducing autophagy. Sci Rep. 2020;10(1):3107. https://doi.org/10.1038/s41598-020-59474-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Lallès JP. Long term effects of pre- and early postnatal nutrition and environment on the gut. J Anim Sci. 2012;90(Suppl 4):421–9. https://doi.org/10.2527/jas.53904.

    Article  PubMed  Google Scholar 

  59. Martínez-Moya P, Ortega-González M, González R, Anzola A, Ocón B, Hernández-Chirlaque C, et al. Exogenous alkaline phosphatase treatment complements endogenous enzyme protection in colonic inflammation and reduces bacterial translocation in rats. Pharmacol Res. 2012;66(2):144–53. https://doi.org/10.1016/j.phrs.2012.04.006.

    Article  CAS  PubMed  Google Scholar 

  60. Riggle KM, Rentea RM, Welak SR, Pritchard KA Jr, Oldham KT, Gourlay DM. Intestinal alkaline phosphatase prevents the systemic inflammatory response associated with necrotizing enterocolitis. J Surg Res. 2013;180(1):21–6. https://doi.org/10.1016/j.jss.2012.10.042.

    Article  CAS  PubMed  Google Scholar 

  61. Alam SN, Yammine H, Moaven O, Ahmed R, Moss AK, Biswas B, et al. Intestinal alkaline phosphatase prevents antibiotic-induced susceptibility to enteric pathogens. Ann Surg. 2014;259(4):715–22. https://doi.org/10.1097/SLA.0b013e31828fae14.

    Article  PubMed  Google Scholar 

  62. Larrick JW, Mendelsohn AR. Supplementation with brush border enzyme alkaline phosphatase slows aging. Rejuvenation Res. 2020;23(2):171–5. https://doi.org/10.1089/rej.2020.2335.

    Article  CAS  PubMed  Google Scholar 

  63. Kaliannan K, Hamarneh SR, Economopoulos KP, Nasrin Alam S, Moaven O, Patel P, et al. Intestinal alkaline phosphatase prevents metabolic syndrome in mice. Proc Natl Acad Sci U S A. 2013;110(17):7003–8. https://doi.org/10.1073/pnas.1220180110.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Economopoulos KP, Ward NL, Phillips CD, Teshager A, Patel P, Mohamed MM, et al. Prevention of antibiotic-associated metabolic syndrome in mice by intestinal alkaline phosphatase. Diabetes Obes Metab. 2016;18(5):519–27. https://doi.org/10.1111/dom.12645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kühn F, Adiliaghdam F, Cavallaro PM, Hamarneh SR, Tsurumi A, Hoda RS, et al. Intestinal alkaline phosphatase targets the gut barrier to prevent aging. JCI Insight. 2020;5(6):e134049. https://doi.org/10.1172/jci.insight.134049.

    Article  PubMed Central  Google Scholar 

  66. Davidson JA, Khailova L, Treece A, Robison J, Soranno DE, Jaggers J, et al. Alkaline phosphatase treatment of acute kidney injury in an infant piglet model of cardiopulmonary bypass with deep hypothermic circulatory arrest. Sci Rep. 2019;9(1):14175. https://doi.org/10.1038/s41598-019-50481-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Plaeke P, De Man JG, Smet A, Malhotra-Kumar S, Pintelon I, Timmermans JP, et al. Effects of intestinal alkaline phosphatase on intestinal barrier function in a cecal ligation and puncture (CLP)-induced mouse model for sepsis. Neurogastroenterol Motil. 2020;32(3):e13754. https://doi.org/10.1111/nmo.13754.

    Article  CAS  PubMed  Google Scholar 

  68. Pickkers P, Mehta RL, Murray PT, Joannidis M, Molitoris BA, Kellum JA, et al. Effect of human recombinant alkaline phosphatase on 7-day creatinine clearance in patients with sepsis-associated acute kidney injury: a randomized clinical trial. JAMA. 2018;320(19):1998–2009. https://doi.org/10.1001/jama.2018.14283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Peters E, Stevens J, Arend J, Guan Z, Raaben W, Laverman P, et al. Biodistribution and translational pharmacokinetic modeling of a human recombinant alkaline phosphatase. Int J Pharm. 2015;495(1):122–31. https://doi.org/10.1016/j.ijpharm.2015.08.090.

    Article  CAS  PubMed  Google Scholar 

  70. Peters E, Ergin B, Kandil A, Gurel-Gurevin E, van Elsas A, Masereeuw R, et al. Effects of a human recombinant alkaline phosphatase on renal hemodynamics, oxygenation and inflammation in two models of acute kidney injury. Toxicol Appl Pharmacol. 2016;313:88–96. https://doi.org/10.1016/j.taap.2016.10.015.

    Article  CAS  PubMed  Google Scholar 

  71. Brun LR, Brance ML, Rigalli A. Luminal calcium concentration controls intestinal calcium absorption by modification of intestinal alkaline phosphatase activity. Br J Nutr. 2012;108(2):229–33. https://doi.org/10.1017/S0007114511005617.

    Article  CAS  PubMed  Google Scholar 

  72. Brun LR, Brance ML, Lombarte M, Lupo M, Di Loreto VE, Rigalli A. Regulation of intestinal calcium absorption by luminal calcium content: role of intestinal alkaline phosphatase. Mol Nutr Food Res. 2014;58(7):1546–51. https://doi.org/10.1002/mnfr.201300686.

    Article  CAS  PubMed  Google Scholar 

  73. Brun LR, Lombarte M, Roma S, Perez F, Millán JL, Rigalli A. Increased calcium uptake and improved trabecular bone properties in intestinal alkaline phosphatase knockout mice. J Bone Miner Metab. 2018;36(6):661–7. https://doi.org/10.1007/s00774-017-0887-7.

    Article  CAS  PubMed  Google Scholar 

  74. Kuehn F, Adiliaghdam F, Hamarneh SR, Vasan R, Liu E, Liu Y, et al. Loss of intestinal alkaline phosphatase leads to distinct chronic changes in bone phenotype. J Surg Res. 2018;232:325–31. https://doi.org/10.1016/j.jss.2018.06.061.

    Article  CAS  PubMed  Google Scholar 

  75. Sasaki S, Segawa H, Hanazaki A, Kirino R, Fujii T, Ikuta K, et al. A role of intestinal alkaline phosphatase 3 (Akp3) in inorganic phosphate homeostasis. Kidney Blood Press Res. 2018;43(5):1409–24. https://doi.org/10.1159/000493379.

    Article  CAS  PubMed  Google Scholar 

  76. Hamarneh SR, Mohamed MM, Economopoulos KP, Morrison SA, Phupitakphol T, Tantillo TJ, et al. A novel approach to maintain gut mucosal integrity using an oral enzyme supplement. Ann Surg. 2014;260(4):706–14. https://doi.org/10.1097/SLA.0000000000000916.

    Article  PubMed  Google Scholar 

  77. Rentea RM, Rentea MJ, Biesterveld B, Liedel JL, Gourlay DM. Factors known to influence the development of necrotizing enterocolitis to modify expression and activity of intestinal alkaline phosphatase in a newborn neonatal rat model. Eur J Pediatr Surg. 2019;29(3):290–7. https://doi.org/10.1055/s-0038-1646959.

    Article  PubMed  Google Scholar 

  78. Navis M, Muncan V, Sangild PT, Møller Willumsen L, Koelink PJ, Wildenberg ME, et al. Beneficial effect of mildly pasteurized whey protein on intestinal integrity and innate defense in preterm and near-term piglets. Nutrients. 2020;12(4):1125. https://doi.org/10.3390/nu12041125.

    Article  CAS  PubMed Central  Google Scholar 

  79. Yu JC, Khodadadi H, Baban B. Innate immunity and oral microbiome: a personalized, predictive, and preventive approach to the management of oral diseases. EPMA J. 2019;10(1):43–50. https://doi.org/10.1007/s13167-019-00163-4.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Мokrozub VV, Lazarenko LM, Sichel LM, Babenko LP, Lytvyn PM, Demchenko OM, et al. The role of beneficial bacteria wall elasticity in regulating innate immune response. EPMA J. 2015;6(1):13. https://doi.org/10.1186/s13167-015-0035-1.

    Article  Google Scholar 

  81. Vir P, Kaur J, Mahmood A. Effect of chronic iron ingestion on the development of brush border enzymes in rat intestine. Toxicol Mech Methods. 2007;17(7):393–9. https://doi.org/10.1080/15376510601102793.

    Article  CAS  PubMed  Google Scholar 

  82. Kaliannan K, Wang B, Li XY, Kim KJ, Kang JX. A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia. Sci Rep. 2015;5:11276. https://doi.org/10.1038/srep11276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Šefčíková Z, Bujňáková D. Effect of pre- and post-weaning high-fat dietary manipulation on intestinal microflora and alkaline phosphatase activity in male rats. Physiol Res. 2017;66(4):677–85. https://doi.org/10.33549/physiolres.933500.

    Article  PubMed  Google Scholar 

  84. Montagne L, Toullec R, Savidge T, Lallès JP. Morphology and enzyme activities of the small intestine are modulated by dietary protein source in the preruminant calf. Reprod Nutr Dev. 1999;39(4):455–66. https://doi.org/10.1051/rnd:19990405.

    Article  CAS  PubMed  Google Scholar 

  85. Boudry G, Lallès JP, Malbert CH, Bobillier E, Sève B. Diet-related adaptation of the small intestine at weaning in pigs is functional rather than structural. J Pediatr Gastroenterol Nutr. 2002;34(2):180–7. https://doi.org/10.1097/00005176-200202000-00014.

    Article  CAS  PubMed  Google Scholar 

  86. Thoreux K, Balas D, Bouley C, Senegas-Balas F. Diet supplemented with yoghurt or milk fermented by Lactobacillus casei DN-114 001 stimulates growth and brush-border enzyme activities in mouse small intestine. Digestion. 1998;59(4):349–59. https://doi.org/10.1159/000007514.

    Article  CAS  PubMed  Google Scholar 

  87. Montoya CA, Leterme P, Lalles JP. A protein-free diet alters small intestinal architecture and digestive enzyme activities in rats. Reprod Nutr Dev. 2006;46(1):49–56. https://doi.org/10.1051/rnd:2005063.

    Article  CAS  PubMed  Google Scholar 

  88. Sogabe N, Mizoi L, Asahi K, Ezawa I, Goseki-Sone M. Enhancement by lactose of intestinal alkaline phosphatase expression in rats. Bone. 2004;35(1):249–55. https://doi.org/10.1016/j.bone.2004.02.007.

    Article  CAS  PubMed  Google Scholar 

  89. Okazaki Y, Katayama T. Glucomannan consumption elevates colonic alkaline phosphatase activity by up-regulating the expression of IAP-I, which is associated with increased production of protective factors for gut epithelial homeostasis in high-fat diet-fed rats. Nutr Res. 2017;43:43–50. https://doi.org/10.1016/j.nutres.2017.05.012.

    Article  CAS  PubMed  Google Scholar 

  90. Okazaki Y, Katayama T. Consumption of non-digestible oligosaccharides elevates colonic alkaline phosphatase activity by up-regulating the expression of IAP-I, with increased mucins and microbial fermentation in rats fed a high-fat diet. Br J Nutr. 2019;121(2):146–54. https://doi.org/10.1017/S0007114518003082.

    Article  CAS  PubMed  Google Scholar 

  91. Erdijk O, van Baarlen P, Fernandez-Gutierrez MM, van den Brink E, Schuren FHJ, Brugman S, et al. Sialyllactose and galactooligosaccharides promote epithelial barrier functioning and distinctly modulate microbiota composition and short chain fatty acid production in vitro. Front Immunol. 2019;10:94. https://doi.org/10.3389/fimmu.2019.00094.

    Article  CAS  Google Scholar 

  92. Nakaoka K, Tanabe R, Oku Y. Influences of vitamin D restriction on alkaline phosphatase activity in rats fed a high-fat diet. J Jpn Soc Nutr Food Sci. 2016;69:57–63. https://doi.org/10.4327/jsnfs.69.57.

    Article  CAS  Google Scholar 

  93. Nakaoka K, Yamada A, Noda S, Goseki-Sone M. Vitamin D-restricted high-fat diet down-regulates expression of intestinal alkaline phosphatase isozymes in ovariectomized rats. Nutr Res. 2018;53:23–31. https://doi.org/10.1016/j.nutres.2018.03.001.

    Article  CAS  PubMed  Google Scholar 

  94. Sogabe N, Maruyama R, Hosori T, Goseki-Sone M. Enhancement effects of vitamin K1 (phylloquinone) or vitamin K2 (menaquinone-4) on intestinal alkaline phosphatase activity in rats. J Nutr Sci Vitaminol (Tokyo). 2007;53(3):219–24. https://doi.org/10.3177/jnsv.53.219.

    Article  CAS  Google Scholar 

  95. Haraikawa M, Sogabe N, Tanabe R, Hosoi T, Goseki-Sone M. Vitamin K1 (phylloquinone) or vitamin K2 (menaquinone-4) induces intestinal alkaline phosphatase gene expression. J Nutr Sci Vitaminol (Tokyo). 2011;57(4):274–9. https://doi.org/10.3177/jnsv.57.274.

    Article  CAS  Google Scholar 

  96. Ghosh SS, Gehr TW, Ghosh S. Curcumin and chronic kidney disease (CKD): major mode of action through stimulating endogenous intestinal alkaline phosphatase. Molecules. 2014;19(12):20139–56. https://doi.org/10.3390/molecules191220139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Ghosh SS, He H, Wang J, Gehr TW, Ghosh S. Curcumin-mediated regulation of intestinal barrier function: the mechanism underlying its beneficial effects. Tissue Barriers. 2018;6(1):e1425085. https://doi.org/10.1080/21688370.2018.1425085.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Ghosh SS, Bie J, Wang J, Ghosh S. Oral supplementation with non-absorbable antibiotics or curcumin attenuates western diet-induced atherosclerosis and glucose intolerance in LDLR-/- mice--role of intestinal permeability and macrophage activation. PLoS One. 2014;9(9):e108577. https://doi.org/10.1371/journal.pone.0108577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Ghosh SS, He H, Wang J, Korzun W, Yannie PJ, Ghosh S. Intestine-specific expression of human chimeric intestinal alkaline phosphatase attenuates Western diet-induced barrier dysfunction and glucose intolerance. Phys Rep. 2018;6(14):e13790. https://doi.org/10.14814/phy2.13790.

    Article  CAS  Google Scholar 

  100. Prakash UN, Srinivasan K. Beneficial influence of dietary spices on the ultrastructure and fluidity of the intestinal brush border in rats. Br J Nutr. 2010;104(1):31–9. https://doi.org/10.1017/S0007114510000334.

    Article  CAS  PubMed  Google Scholar 

  101. Pereira MT, Malik M, Nostro JA, Mahler GJ, Musselman LP. Effect of dietary additives on intestinal permeability in both Drosophila and a human cell co-culture. Dis Model Mech. 2018;11(12):dmm034520. https://doi.org/10.1242/dmm.034520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Srigiridhar K, Nair KM. Iron-deficient intestine is more susceptible to peroxidative damage during iron supplementation in rats. Free Radic Biol Med. 1998;25(6):660–5. https://doi.org/10.1016/s0891-5849(98)00086-0.

    Article  CAS  PubMed  Google Scholar 

  103. Bubnov RV, Spivak MY, Lazarenko LM, Bomba A, Boyko NV. Probiotics and immunity: provisional role for personalized diets and disease prevention. EPMA J. 2015;6(1):14. https://doi.org/10.1186/s13167-015-0036-0.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Reid G, Abrahamsson T, Bailey M, Bindels LB, Bubnov R, Ganguli K, et al. How do probiotics and prebiotics function at distant sites? Benefic Microbes. 2017;8(4):521–33. https://doi.org/10.3920/BM2016.0222.

    Article  CAS  Google Scholar 

  105. Bubnov RV, Babenko LP, Lazarenko LM, Mokrozub VV, Spivak MY. Specific properties of probiotic strains: relevance and benefits for the host. EPMA J. 2018;9(2):205–23. https://doi.org/10.1007/s13167-018-0132-z.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Bubnov R, Babenko L, Lazarenko L, Kryvtsova M, Shcherbakov O, Zholobak N, et al. Can tailored nanoceria act as a prebiotic? Report on improved lipid profile and gut microbiota in obese mice. EPMA J. 2019;10(4):317–35. https://doi.org/10.1007/s13167-019-00190-1.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Abdelhamid AG, El-Masry SS, El-Dougdoug NK. Probiotic Lactobacillus and Bifidobacterium strains possess safety characteristics, antiviral activities and host adherence factors revealed by genome mining. EPMA J. 2019;10(4):337–50. https://doi.org/10.1007/s13167-019-00184-z.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Borges NA, Carmo FL, Stockler-Pinto MB, de Brito JS, Dolenga CJ, Ferreira DC, et al. Probiotic supplementation in chronic kidney disease: a double-blind, randomized, Placebo-Controlled Trial. J Ren Nutr. 2018;28(1):28–36. https://doi.org/10.1053/j.jrn.2017.06.010.

    Article  CAS  PubMed  Google Scholar 

  109. Ermolenko E, Gromova L, Borschev Y, Voeikova A, Karaseva A, Ermolenko K, et al. Influence of different probiotic lactic acid bacteria on microbiota and metabolism of rats with dysbiosis. Biosci Microbiota Food Health. 2013;32(2):41–9. https://doi.org/10.12938/bmfh.32.41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Symonds EL, O'Mahony C, Lapthorne S, O'Mahony D, Sharry JM, O'Mahony L, et al. Bifidobacterium infantis 35624 protects against salmonella-induced reductions in digestive enzyme activity in mice by attenuation of the host inflammatory response. Clin Transl Gastroenterol. 2012;3(5):e15. https://doi.org/10.1038/ctg.2012.9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Said A, Desai C, Lerma EV. Chronic kidney disease. Dis Mon. 2015;61(9):374–7. https://doi.org/10.1016/j.disamonth.2015.08.001.

    Article  PubMed  Google Scholar 

  112. Baumgarten M, Gehr T. Chronic kidney disease: detection and evaluation. Am Fam Physician. 2011;84(10):1138–48.

    PubMed  Google Scholar 

  113. Konopelniuk VV, Goloborodko II, Ishchuk TV, Synelnyk TB, Ostapchenko LI, Spivak MY, et al. Efficacy of Fenugreek-based bionanocomposite on renal dysfunction and endogenous intoxication in high-calorie diet-induced obesity rat model-comparative study. EPMA J. 2017;8(4):377–90. https://doi.org/10.1007/s13167-017-0098-2.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Mafra D, Lobo JC, Barros AF, Koppe L, Vaziri ND, Fouque D. Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease. Future Microbiol. 2014;9(3):399–410. https://doi.org/10.2217/fmb.13.165.

    Article  CAS  PubMed  Google Scholar 

  115. Vaziri ND. CKD impairs barrier function and alters microbial flora of the intestine: a major link to inflammation and uremic toxicity. Curr Opin Nephrol Hypertens. 2012;21(6):587–92. https://doi.org/10.1097/MNH.0b013e328358c8d5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Vaziri ND, Freel RW, Hatch M. Effect of chronic experimental renal insufficiency on urate metabolism. J Am Soc Nephrol. 1995;6(4):1313–7.

    CAS  PubMed  Google Scholar 

  117. Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219–32. https://doi.org/10.1038/nri.2017.7.

    Article  CAS  PubMed  Google Scholar 

  118. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220–30. https://doi.org/10.1038/nature11550.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Vaziri ND, Yuan J, Rahimi A, Ni Z, Said H, Subramanian VS. Disintegration of colonic epithelial tight junction in uremia: a likely cause of CKD-associated inflammation. Nephrol Dial Transplant. 2012;27(7):2686–93. https://doi.org/10.1093/ndt/gfr624.

    Article  CAS  PubMed  Google Scholar 

  120. Vaziri ND, Wong J, Pahl M, Piceno YM, Yuan J, DeSantis TZ, et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 2013;83(2):308–15. https://doi.org/10.1038/ki.2012.345.

    Article  PubMed  Google Scholar 

  121. Manco M, Putignani L, Bottazzo GF. Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev. 2010;31(6):817–44. https://doi.org/10.1210/er.2009-0030.

    Article  CAS  PubMed  Google Scholar 

  122. Mafra D, Barros AF, Fouque D. Dietary protein metabolism by gut microbiota and its consequences for chronic kidney disease patients. Future Microbiol. 2013;8(10):1317–23. https://doi.org/10.2217/fmb.13.103.

    Article  CAS  PubMed  Google Scholar 

  123. Lau WL, Kalantar-Zadeh K, Vaziri ND. The gut as a source of inflammation in chronic kidney disease. Nephron. 2015;130(2):92–8. https://doi.org/10.1159/000381990.

    Article  CAS  PubMed  Google Scholar 

  124. Lehto M, Groop PH. The gut-kidney axis: putative interconnections between gastrointestinal and renal disorders. Front Endocrinol (Lausanne). 2018;9:553. https://doi.org/10.3389/fendo.2018.00553.

    Article  Google Scholar 

  125. Yang Y, Rader E, Peters-Carr M, Bent RC, Smilowitz JT, Guillemin K, et al. Ontogeny of alkaline phosphatase activity in infant intestines and breast milk. BMC Pediatr. 2019;19(1):2. https://doi.org/10.1186/s12887-018-1379-1.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Van Hoof VO, De Broe ME. Interpretation and clinical significance of alkaline phosphatase isoenzyme patterns. Crit Rev Clin Lab Sci. 1994;31(3):197–293. https://doi.org/10.3109/10408369409084677.

    Article  PubMed  Google Scholar 

  127. Alpers DH, DeSchryver-Kecskemeti K, Goodwin CL, Tindira CA, Harter H, Slatopolsky E. Intestinal alkaline phosphatase in patients with chronic renal failure. Gastroenterology. 1988;94(1):62–7. https://doi.org/10.1016/0016-5085(88)90610-5.

    Article  CAS  PubMed  Google Scholar 

  128. Ramezani A, Raj DS. The gut microbiome, kidney disease, and targeted interventions. J Am Soc Nephrol. 2014;25(4):657–70. https://doi.org/10.1681/ASN.2013080905.

    Article  CAS  PubMed  Google Scholar 

  129. Vaziri ND, Zhao YY, Pahl MV. Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature, mechanisms, consequences and potential treatment. Nephrol Dial Transplant. 2016;31(5):737–46. https://doi.org/10.1093/ndt/gfv095.

    Article  CAS  PubMed  Google Scholar 

  130. Esgalhado M, Kemp JA, Damasceno NR, Fouque D, Mafra D. Short-chain fatty acids: a link between prebiotics and microbiota in chronic kidney disease. Future Microbiol. 2017;12:1413–25. https://doi.org/10.2217/fmb-2017-0059.

    Article  CAS  PubMed  Google Scholar 

  131. Koppe L, Fouque D. Microbiota and prebiotics modulation of uremic toxin generation. Panminerva Med. 2017;59(2):173–87. https://doi.org/10.23736/S0031-0808.16.03282-1.

    Article  PubMed  Google Scholar 

  132. Mafra D, Borges N, Alvarenga L, Esgalhado M, Cardozo L, Lindholm B, et al. Dietary components that may influence the disturbed gut microbiota in chronic kidney disease. Nutrients. 2019;11(3):496. https://doi.org/10.3390/nu11030496.

    Article  CAS  PubMed Central  Google Scholar 

  133. Mafra D, Borges NA, Lindholm B, Shiels PG, Evenepoel P, Stenvinkel P. Food as medicine: targeting the uraemic phenotype in chronic kidney disease. Nat Rev Nephrol. 2020. https://doi.org/10.1038/s41581-020-00345-8.

  134. Johnson IT, Gee JM, Mahoney RR. Effect of dietary supplements of guar gum and cellulose on intestinal cell proliferation, enzyme levels and sugar transport in the rat. Br J Nutr. 1984;52(3):477–87. https://doi.org/10.1079/bjn19840115.

    Article  CAS  PubMed  Google Scholar 

  135. Kaur J, Madan S, Hamid A, Singla A, Mahmood A. Intestinal alkaline phosphatase secretion in oil-fed rats. Dig Dis Sci. 2007;52(3):665–70. https://doi.org/10.1007/s10620-006-9384-x.

    Article  CAS  PubMed  Google Scholar 

  136. Walker AW. Intestinal alkaline phosphatase in serum of patients on maintenance haemodialysis. Clin Chim Acta. 1974 Sep 30;55(3):399–405. https://doi.org/10.1016/0009-8981(74)90015-1.

    Article  CAS  PubMed  Google Scholar 

  137. De Broe ME, Bosteels V, Wieme RJ. Letter: increased intestinal alkaline phosphatase in serum of patients on maintenance haemodialysis. Lancet. 1974;1(7860):753–4. https://doi.org/10.1016/s0140-6736(74)92980-8.

    Article  PubMed  Google Scholar 

  138. Skillen AW, Pierides AM. Serum alkaline phosphatase isoenzyme patterns in patients with chronic renal failure. Clin Chim Acta. 1977;80(2):339–46. https://doi.org/10.1016/0009-8981(77)90042-0.

    Article  CAS  PubMed  Google Scholar 

  139. Stĕpán J, Havránek T, Jelínková E, Straková M, Skrha J, Pacovský V. Metabolic implications in the elevation of serum activity of intestinal alkaline phosphatase in chronic renal failure. Experientia. 1984;40(8):896–8. https://doi.org/10.1007/BF01952015.

    Article  PubMed  Google Scholar 

  140. Tibi L, Chhabra SC, Sweeting VM, Winney RJ, Smith AF. Multiple forms of alkaline phosphatase in plasma of hemodialysis patients. Clin Chem. 1991 Jun;37(6):815–20.

    Article  CAS  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Post Graduation Program in Medical Sciences, (UFF) Federal Fluminense University Niterói-Rio de Janeiro (RJ), Niterói, Brazil

    L. Alvarenga & D. Mafra

  2. Post Graduation Program in Cardiovascular Sciences, Federal Fluminense University (UFF), Niterói, Rio de Janeiro (RJ), Brazil

    L. F. M. F. Cardozo & D. Mafra

  3. Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Technology and Intervention, Karolinska Institutet, Stockholm, Sweden

    B. Lindholm & P. Stenvinkel

Authors
  1. L. Alvarenga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. F. M. F. Cardozo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Lindholm
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Stenvinkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. Mafra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Alvarenga.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13167-020-00228-9

Keywords

Search

Navigation