FGF23, αKLOTHO AND VITAMIN D MEDIATED CALCIUM-PHOSPHATE METABOLISM IN HEMODIALYSIS PATIENTS

FGF23, αKlotho, Vitamin D and Ca-P in Hemodialysis

DOI: https://doi.org/10.5937/jomb0-27408
Keywords: Calcium-phosphate metabolism, FGF23, Hemodialysis, Vitamin D, αKlotho

Abstract


Background: Klotho is a protein that acts as a co-receptor for FGF23. FGF23-Klotho axis has great importance regarding to the regulation of mineral metabolism by kidneys. In this study, we analyzed FGF23, αKlotho, 1,25-dihydroxyvitamin D3, 25-hydroxyvitamin D, parathormone, calcium and phosphate levels of hemodialysis patients in order to investigate the nature of the mineral metabolism disruption in chronic kidney diseases.

Methods: Sixty hemodialysis patients and 34 healthy controls were included in the study. Serum iFGF, cFGF, soluble αKlotho were analyzed using ELISA kits. 1,25-dihydroxyvitamin D3 was determined using LC-MS/MS. Calcium, phosphate, iPTH and 25-hydroxyvitamin D were measured using autoanalyzers.

Results: In hemodialysis patients, iFGF23, cFGF23, iPTH and P levels were significantly higher and 1,25-dihydroxyvitamin D3, αKlotho and Ca levels were significantly lower compared with the control group. There was no significant difference in 25-hydroxyvitamin D levels.

Conclusion: Our study showed that lack of sufficient amounts of αKlotho is crucial for mineral metabolism disruptions seen as a complication of chronic kidney diseases. Despite the high levels of the hormone, FGF23 is unable to accomplish its function properly, likely due to deteriorated kidney function in hemodialysis patients.

Author Biographies

Ozge Tugce Pasaoglu, Gazi University, Faculty of Health Sciences

Department of Nutrition and Dietetics, PhD

Ayse Senelmis, Gazi University, Faculty of Medicine

Department of Medical Biochemistry, PhD

Ozant Helvaci, Gazi University, Faculty of Medicine

Department of Internal Medicine, Section of Nephrology, MD

Ulver Derici, Gazi University, Faculty of Medicine

Department of Internal Medicine, Section of Nephrology, Professor

Hatice Pasaoglu, Gazi University, Faculty of Medicine

Department of Medical Biochemistry, Professor

References

1. Moe S, Drüeke T, Cunningham J, Goodman W, Martin K, et al. Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney international. 2006;69(11):1945-53.
2. Moe SM, Drüeke T. Improving global outcomes in mineral and bone disorders. Clinical journal of the American Society of Nephrology. 2008;3(Supplement 3):S127-S30.
3. Meyer Jr RA, Meyer MH, Tenenhouse HS, Klugerman AH. The renal phosphate transport defect in normal mice parabiosed to X‐linked hypophosphatemic mice persists after parathyroidectomy. Journal of Bone and Mineral Research. 1989;4(4):523-32.
4. Eddington H, Hoefield R, Sinha S, Chrysochou C, Lane B, et al. Serum phosphate and mortality in patients with chronic kidney disease. Clinical Journal of the American Society of Nephrology. 2010;5(12):2251-7.
5. Takashi Y, Fukumoto S. FGF23-Klotho axis in CKD. Renal Replacement Therapy. 2016;2(1):20.
6. Liu Z, Zhou H, Chen X, Chen H, Wang Y, et al. Relationship between cFGF23/Klotho ratio and phosphate levels in patients with chronic kidney disease. International urology and nephrology. 2019;51(3):503-7.
7. Denic A, Lieske JC, Chakkera HA, Poggio ED, Alexander MP, et al. The substantial loss of nephrons in healthy human kidneys with aging. Journal of the American Society of Nephrology. 2017;28(1):313-20.
8. Hu MC, Shiizaki K, Kuro-o M, Moe OW. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annual review of physiology. 2013;75:503-33.
9. Isakova T, Wahl P, Vargas GS, Gutierrez OM, Scialla J, et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int. 2011;79(12):1370-8. DOI: 10.1038/ki.2011.47.
10. Kuro OM. Klotho and endocrine fibroblast growth factors: markers of chronic kidney disease progression and cardiovascular complications? Nephrol Dial Transplant. 2019;34(1):15-21. DOI: 10.1093/ndt/gfy126.
11. Nitta K, Nagano N, Tsuchiya K. Fibroblast growth factor 23/klotho axis in chronic kidney disease. Nephron Clinical Practice. 2014;128(1-2):1-10.
12. Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006;444(7120):770-4. DOI: 10.1038/nature05315.
13. Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, et al. Regulation of fibroblast growth factor-23 signaling by klotho. Journal of Biological Chemistry. 2006;281(10):6120-3.
14. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. nature. 1997;390(6655):45.
15. Lu X, Hu MC. Klotho/FGF23 axis in chronic kidney disease and cardiovascular disease. Kidney Diseases. 2017;3(1):15-23.
16. Koh N, Fujimori T, Nishiguchi S, Tamori A, Shiomi S, et al. Severely reduced production of klotho in human chronic renal failure kidney. Biochemical and biophysical research communications. 2001;280(4):1015-20.
17. Seiler S, Heine GH, Fliser D. Clinical relevance of FGF-23 in chronic kidney disease. Kidney International. 2009;76:S34-S42.
18. Lavi-Moshayoff V, Silver J, Naveh-Many T. Human PTH gene regulation in vivo using transgenic mice. American Journal of Physiology-Renal Physiology. 2009;297(3):F713-F9.
19. Razzaque MS, Lanske B. The emerging role of the fibroblast growth factor-23–klotho axis in renal regulation of phosphate homeostasis. The Journal of endocrinology. 2007;194(1):1.
20. Pavik I, Jaeger P, Ebner L, Wagner CA, Petzold K, et al. Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence suggested from a cross-sectional study. Nephrology Dialysis Transplantation. 2012;28(2):352-9.
21. Sakan H, Nakatani K, Asai O, Imura A, Tanaka T, et al. Reduced renal α-Klotho expression in CKD patients and its effect on renal phosphate handling and vitamin D metabolism. PloS one. 2014;9(1):e86301.
22. Kim HR, Nam BY, Kim DW, Kang MW, Han J-H, et al. Circulating α-klotho levels in CKD and relationship to progression. American Journal of Kidney Diseases. 2013;61(6):899-909.
23. Shibata K, Fujita S, Morita H, Okamoto Y, Sohmiya K, et al. Association between circulating fibroblast growth factor 23, alpha-Klotho, and the left ventricular ejection fraction and left ventricular mass in cardiology inpatients. PLoS One. 2013;8(9):e73184. DOI: 10.1371/journal.pone.0073184.
24. Rotondi S, Pasquali M, Tartaglione L, Muci ML, Mandanici G, et al. Soluble α-Klotho serum levels in chronic kidney disease. International journal of endocrinology. 2015;2015.
25. Seiler S, Wen M, Roth HJ, Fehrenz M, Flügge F, et al. Plasma Klotho is not related to kidney function and does not predict adverse outcome in patients with chronic kidney disease. Kidney international. 2013;83(1):121-8.
Published
2020/09/08
Issue
Vol. 40 No. 2 (2021): Journal of Medical Biochemistry
Section
Original paper

Copyright (c) 2020 Ozge Tugce Pasaoglu, Ayse Senelmis, Ozant Helvaci, Ulver Derici, Hatice Pasaoglu

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