The serum level of the morphogenetic protein fibroblast growth factor 23 (FGF-23) as a marker for the efficiency of hyperphosphatemia therapy with phosphate-binding agents in chronic kidney disease


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Abstract

Aim. To study whether the excessive production of serum fibroblast growth factor 23 (FGF-23) may be reduced with phosphate-binding agents to treat hyperphosphatemia in patients with Stage VD chronic kidney disease (CKD). Subjects and methods. The investigation enrolled 25 patients with Stage VD CKD on regular hemodialysis (HD) (12 patients with chronic glomerulonephritis, 8 with tubulointerstitial nephritis, and 5 with hypertensive nephrosclerosis); among them there were 15 men and 10 women at the age of 21 to 65 years; their mean age at inclusion in the study was 43±4.5 years. The clinical, laboratory, and instrumental examination similar to that in patients with the early stages of CKD was done. Serum FGF-23 levels (Human FGF-23 ELISA kit using monoclonal antibodies to the full FGF-23 molecule) were investigated in all the 25 patients. A whole blood sample was taken 2 days after the last session of HD before initiation of its regular procedure. Results. The elevated serum FGF-23 concentrations in the patients on regular HD correlated with their HD duration (r=0.508; p<0.001). Along with this, a strong direct correlation (r=0.522; p<0.001) was found between the concentration of FGF-23 in the serum and inorganic phosphorus; at the same time hyperphosphatemia was less significantly associated with higher serum intact parathyroid hormone (PTH) levels (r=0.398; p<0.05). Lower FGF-23 and PHT levels were noted in a group of patients who could achieve and maintain the target serum inorganic phosphorus level (0.9—1.45 mmol/l) compared to that of patients with uncorrected hyperphosphatemia (>1.45 mmol/l) (p<0.01). A decrease in FGF-23 and PHT levels was achieved chiefly in the patients who had used phosphate-binders that contained no calcium (sevelamer hydrochloride). Conclusion. Lower FGF-23 levels were observed in the patients with CHD on regular HD who can achieve and maintain the target serum inorganic phosphorus level when using phosphate-binders that do not contain calcium than in those with uncorrected hyperphosphatemia (p<0.01).

References

  1. Gutiérrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Lee H, Thadhani R, Juppner H, Wold M. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Eng J Med. 2008;359(6):584-592. doi: 10.1056/NEJMoa0706130.
  2. Yilmaz MI, Sonmez A, Saglam M, Yaman HI, Kilic S, Demirkaya E, Eyileten T, Caglar K, Oguz Y, Vural A, Yenicesu M. and Zoccali C. FGF-23 and vascular dysfunction in atients with stage 3 and 4 chronic kidney disease. Kidney Int. 2010;78:679-685. doi: 10.1038/ki.2010.194.
  3. Милованова Л.Ю., Милованов Ю.С., Козловская Л.В., Мухин Н.А. Сывороточные уровни морфогенетических белков — фактора роста фибробластов-23 (FGF-23) и Клото (Klotho) при ХБП: клиническое значение. Клиническая нефрология. 2013;2:10-18. doi: 10.2331/susian. 32.804.
  4. Milovanova L, Milovanov Y, Plotnikova A. Phosphorus and Calcium Metabolism Disorders Assosiated with Chronic Kidney Disease Stage III—IV (Systematic Review and Meta-Analysis). Chronic Kidney Disease and renal Transplantation. Ed. by Manisha Sahay. INTECH; 2012. doi: 10.1037/0003-066x.59.1.29.
  5. Милованова Л.Ю., Милованов Ю.С., Крюкова Д.В. Клиническое значение фактора роста фибробластов-23 (FGF-23) и белка Klotho при хронической болезни почек. Клиническая фармакология и терапия. 2013;22(4):1-5. doi:10/ct8vzd.
  6. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic Kidney Disease and the risks of death, cardiovascular events, and hospitalization. N Eng J Med. 2004;351(13):1296-1305. doi: 10.1056/NEJMoa041031.
  7. Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro-o M, Mohammadi M, Sirkis R, Neveh-Many T, Silver J. The parathyroid is a target organ for FGF-23 in rats. J Clin Invest. 2007;117:4003-4008 doi: 10.1172/JCI32409.
  8. Maizel J, Six I, Dupont S. Secq E, Dehedin B, Barreto FC, Benchitrit Joyce, Poirot S, Slama M, Tribouilloy C, Choukroun G, Mazière JC, Drueke TB. Massy ZA. Effects of sevelamer treatment on cardiovascular abnormalities in mice with chronic renal failure. Kidney Int. 2013;84:491-500. doi: 10.1038/ki.2013.110.
  9. Craver L, Marco MP, Martinez JM, Rue M, Borras M, Martin ML, Sarro F, Valdivieldso JM, Fernandez E. Mineral metabolism parameters throughout chronic kidney disease stages 1-5-achievement of K/DOQI target ranges. Nephrol Dial Transplant. 2007;22:1171-1176. doi: 10.1093/ndt/gfl718.
  10. Hu MC, Kuro-o M, Moe OW. Selected Klotho and Chronic Kidney disease. Advanc Exper Med Biol. 2012;728:126-157. doi: 10.1007/978-1-4614-0887-1_9.
  11. Shimada T, Yamazaki Y, Hasegawa H, Muto T, Hino R, Takeuchi Y, Nakahara K, Fujita T, Fukumoto S, Yamashita T. FGF-23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis. J Bon Min Res. 2004;19(4):429-435. doi: 10.1359/JBMR.0301264.

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