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Phosphate toxicity: a stealth biochemical stress factor?

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Fig. 1

References

  1. Moe SM, Zidehsarai MP, Chambers MA, Jackman LA, Radcliffe JS, Trevino LL, Donahue SE, Asplin JR (2011) Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. Clin J Am Soc Nephrol 6:257–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Biber J, Custer M, Magagnin S, Hayes G, Werner A, Lotscher M, Kaissling B, Murer H (1996) Renal Na/Pi-cotransporters. Kidney Int 49:981–985

    Article  CAS  PubMed  Google Scholar 

  3. Brown RB, Razzaque MS (2015) Dysregulation of phosphate metabolism and conditions associated with phosphate toxicity. Bonekey Rep 4:705

    Article  CAS  PubMed  Google Scholar 

  4. Koizumi M, Komaba H, Fukagawa M (2013) Parathyroid function in chronic kidney disease: role of FGF23-Klotho axis. Contrib Nephrol 180:110–123

    Article  CAS  PubMed  Google Scholar 

  5. Razzaque MS (2009) FGF23-mediated regulation of systemic phosphate homeostasis: is Klotho an essential player? Am J Physiol Renal Physiol 296:F470–F476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chen H, Senda T, Kubo KY (2015) The osteocyte plays multiple roles in bone remodeling and mineral homeostasis. Med Mol Morphol 48:61–68

    Article  CAS  PubMed  Google Scholar 

  7. Tenenhouse HS (2005) Regulation of phosphorus homeostasis by the type iia na/phosphate cotransporter. Annu Rev Nutr 25:197–214

    Article  CAS  PubMed  Google Scholar 

  8. Razzaque MS (2009) The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis. Nat Rev Endocrinol 5:611–619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Inoue Y, Segawa H, Kaneko I, Yamanaka S, Kusano K, Kawakami E, Furutani J, Ito M, Kuwahata M, Saito H, Fukushima N, Kato S, Kanayama HO, Miyamoto K (2005) Role of the vitamin D receptor in FGF23 action on phosphate metabolism. Biochem J 390:325–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T (2006) Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 444:770–774

    Article  CAS  PubMed  Google Scholar 

  11. Lanske B, Razzaque MS (2014) Molecular interactions of FGF23 and PTH in phosphate regulation. Kidney Int 86:1072–1074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gaasbeek A, Meinders AE (2005) Hypophosphatemia: an update on its etiology and treatment. Am J Med 118:1094–1101

    Article  CAS  PubMed  Google Scholar 

  13. Shutto Y, Shimada M, Kitajima M, Yamabe H, Razzaque MS (2011) Lack of awareness among future medical professionals about the risk of consuming hidden phosphate-containing processed food and drinks. PLoS One 6:e29105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Shutto Y, Shimada M, Kitajima M, Yamabe H, Saitoh Y, Saitoh H, Razzaque MS (2013) Inadequate awareness among chronic kidney disease patients regarding food and drinks containing artificially added phosphate. PLoS One 8:e78660

    Article  PubMed  PubMed Central  Google Scholar 

  15. Chang AR, Lazo M, Appel LJ, Gutierrez OM, Grams ME (2014) High dietary phosphorus intake is associated with all-cause mortality: results from NHANES III. Am J Clin Nutr 99:320–327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Razzaque MS (2011) Phosphate toxicity: new insights into an old problem. Clin Sci (Lond) 120:91–97

    Article  CAS  Google Scholar 

  17. Razzaque MS (2014) Bone-kidney axis in systemic phosphate turnover. Arch Biochem Biophys 561:154–158

    Article  CAS  PubMed  Google Scholar 

  18. Jin H, Xu CX, Lim HT, Park SJ, Shin JY, Chung YS, Park SC, Chang SH, Youn HJ, Lee KH, Lee YS, Ha YC, Chae CH, Beck GR Jr, Cho MH (2009) High dietary inorganic phosphate increases lung tumorigenesis and alters Akt signaling. Am J Respir Crit Care Med 179:59–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fenninger LD, Waterhouse C, Keutmann EH (1953) The interrelationship of nitrogen and phosphorus in patients with certain neoplastic diseases. Cancer 5:930–941

    Article  Google Scholar 

  20. Elser JJ, Kyle MM, Smith MS, Nagy JD (2007) Biological stoichiometry in human cancer. PLoS One 2:e1028

    Article  PubMed  PubMed Central  Google Scholar 

  21. Center for Nutrition Policy and Promotion (2015) MyPlate resources: sample menus for a 2000 calorie food pattern. http://www.nutrition.gov/smart-nutrition-101/myplate-resources

  22. Mackay EM, Oliver J (1935) Renal damage following the ingestion of a diet containing an excess of inorganic phosphate. J Exp Med 61:319–334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dai XY, Zhao MM, Cai Y, Guan QC, Zhao Y, Guan Y, Kong W, Zhu WG, Xu MJ, Wang X (2013) Phosphate-induced autophagy counteracts vascular calcification by reducing matrix vesicle release. Kidney Int 83:1042–1051

    Article  CAS  PubMed  Google Scholar 

  24. Nguyen TT, Quan X, Hwang KH, Xu S, Das R, Choi SK, Wiederkehr A, Wollheim CB, Cha SK, Park KS (2015) Mitochondrial oxidative stress mediates high-phosphate-induced secretory defects and apoptosis in insulin-secreting cells. Am J Physiol Endocrinol Metab 308:E933–E941

    Article  CAS  PubMed  Google Scholar 

  25. Bourgine A, Beck L, Khoshniat S, Wauquier F, Oliver L, Hue E, Alliot-Licht B, Weiss P, Guicheux J, Wittrant Y (2011) Inorganic phosphate stimulates apoptosis in murine MO6-G3 odontoblast-like cells. Arch Oral Biol 56:977–983

    Article  CAS  PubMed  Google Scholar 

  26. Zhong M, Carney DH, Jo H, Boyan BD, Schwartz Z (2011) Inorganic phosphate induces mammalian growth plate chondrocyte apoptosis in a mitochondrial pathway involving nitric oxide and JNK MAP kinase. Calcif Tissue Int 88:96–108

    Article  CAS  PubMed  Google Scholar 

  27. Meleti Z, Shapiro IM, Adams CS (2000) Inorganic phosphate induces apoptosis of osteoblast-like cells in culture. Bone 27:359–366

    Article  CAS  PubMed  Google Scholar 

  28. Martin C, Schulz R, Rose J, Heusch G (1998) Inorganic phosphate content and free energy change of ATP hydrolysis in regional short-term hibernating myocardium. Cardiovasc Res 39:318–326

    Article  CAS  PubMed  Google Scholar 

  29. Block GA, Wheeler DC, Persky MS, Kestenbaum B, Ketteler M, Spiegel DM, Allison MA, Asplin J, Smits G, Hoofnagle AN, Kooienga L, Thadhani R, Mannstadt M, Wolf M, Chertow GM (2012) Effects of phosphate binders in moderate CKD. J Am Soc Nephrol 23:1407–1415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gutierrez OM, Muntner P, Rizk DV, McClellan WM, Warnock DG, Newby PK, Judd SE (2014) Dietary patterns and risk of death and progression to ESRD in individuals with CKD: a cohort study. Am J Kidney Dis 64:204–213

    Article  PubMed  PubMed Central  Google Scholar 

  31. Blum A (1983) When “More doctors smoked Camels”: cigarette advertising in the Journal. NY State J Med 83:1347–1352

    Google Scholar 

  32. Mahdi AA, Brown RB, Razzaque MS (2015) Osteoporosis in populations with high calcium intake: does phosphate toxicity explain the paradox? Ind J Clin Biochem 30:365–367

    Article  Google Scholar 

  33. Brown RB, Haq A, Stanford CF, Razzaque MS (2015) Vitamin D, phosphate and vasculotoxicity. Can J Physiol Pharmacol. doi:10.1139/cjpp-2015-0083

    PubMed  Google Scholar 

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Acknowledgments

The authors respectfully acknowledge the kind support of late Prof. Takashi Taguchi of Department of Pathology at the Nagasaki University School of Medicine, Nagasaki, Japan in our research. Kidneys of Fig. 1 were processed and stained in his Department.

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Correspondence to Mohammed S. Razzaque.

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Brown, R.B., Razzaque, M.S. Phosphate toxicity: a stealth biochemical stress factor?. Med Mol Morphol 49, 1–4 (2016). https://doi.org/10.1007/s00795-015-0122-3

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