Protein Klotho and FGF23 fibroblasts growth factor as markers of chronic renal disease

A.A. Melnik


Chronic kidney disease (CKD) is a global public health problem in the world. Research scientists are aimed at finding new biomarkers for CKD. Such biomarkers are α-Klotho soluble protein and fibroblast growth factor (FGF23). It was shown that the expression of Klotho protein decreases progressively as the progression of CKD and reaches low or undetectable values at the terminal stage of kidney disease. Unlike Klotho, FGF23 fibroblast growth factor increases in the early stages of CKD and serves as a predictor of an unfavorable clinical outcome. Klotho and FGF23 protein levels are early, sensitive and specific diagnostic biomarkers in CKD and are of diagnostic value for predicting complications of kidney disease.


chronic kidney disease; α-Klotho protein; FGF23 fibroblast growth factor; ELISA


Levey AS, Atkins R, Coresh J, et al. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes. Kidney Int. 2007;72:247-59. doi:10.1038/

Couser WG, Remuzzi G, Mendis S, Tonelli M. The contribution of chronic kidney disease to the global burden of major noncommunicable diseases. Kidney Int. 2011 Dec;80(12):1258-70. doi: 10.1038/ki.2011.368.

Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a synd-rome resembling ageing. Nature 1997;390(6555):45-51. doi:10.1038/36285.

Kurosu H, Yamamoto M, Clark JD, et al. Suppression of aging in mice by the hormone Klotho. Science. 2005;309:1829-33. doi:10.1126/science.1112766.

Nabeshima Y. The discovery of α-Klotho and FGF23 unveiled new insight into calcium and phosphate homeostasis. Cell Mol Life Sci. 2008 Oct;65(20):3218-30. doi: 10.1007/s00018-008-8177-0.

Forster RE, Jurutka PW, Hsieh JC, et al. Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells. Biochem Biophys Res Commun. 2011 Oct 28;414(3):557-62. doi: 10.1016/j.bbrc.2011.09.117.

Hu MC, Shi M, Zhang J, et al. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J. 2010 Sep;24(9):3438-50. doi: 10.1096/fj.10-154765.

Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005;16:139-49. doi: 10.1016/j.cytogfr.2005.01.001.

Mohammadi M, Olsen SK, Ibrahimi OA. Structural basis for fibroblast growth factor receptor activation. Cytokine Growth Factor Rev. 2005;16(2):107–37. doi: 10.1016/j.cytogfr.2005.01.008.

Beenken A, Mohammadi M. The structural biology of the FGF19 subfamily. Adv Exp Med Biol. 2012;728:1-24. doi: 10.1007/978-1-4614-0887-1_1.

Kuro-o M. Endocrine FGFs and Klothos. Austin, TX/New York: Landes Biosci./Springer. 2012. 233 pp.

Goetz R, Beenken A, Ibrahimi OA, et al. Molecular insights into the klotho depen-dent, endocrine mode of action of fibroblast growth factor 19 subfamily members. Mol Cell Biol. 2007;27:3417-28. doi: 10.1128/MCB.02249-06.

Fukumoto S, Yamashita T. Fibroblast growth factor-23 is the phosphaturic factor in tumor-induced osteomalacia and may be phosphatonin. Curr Opin Nephrol Hypertens. 2002;11(4):385-9. PMID: 12105387.

Shimada T, Kakitani M, Yamazaki Y, et al. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest. 2004;113(4):561-8. doi: 10.1172/JCI19081.

Komaba H, Fukagawa M. FGF23: a key player in mineral and bone disorder in CKD Nefrologia. 2009;29(5):392-396. doi:10.3265/Nefrologia.2009.29.5.5400.en.full.

Martin A, David V, Quarles LD. Regulation and function of the FGF23/Klotho endocrine pathways. Physiol Rev. 2012;92:131-55. doi: 10.1152/physrev.00002.2011.

Memon F, El-Abbadi M, Nakatani T. Does Fgf23- klotho activity influence vascular and soft tissue calcification through regulating mineral ion metabolism? Kidney Int. 2008 Sep;74(5):566-70. doi: 10.1038/ki.2008.218.

Urakawa I, Yamazaki Y, Shimada T, et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 2006;444:770-4. doi: 10.1038/nature05315.

Ichikawa S, Imel EA, Kreiter ML, et al. A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Clin Invest 2007;117:2684-91. doi: 10.1172/JCI31330.

Hu MC, Kuro-o M, Moe OW. Klotho and Chronic Kidney Disease. Contrib Nephrol. 2013;180:47-63. doi: 10.1159/000346778.

Shimamura Y, Hamada K, Inoue K, et al. Serum levels of soluble secreted α-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis. Clin Exp Nephrol. 2012 Oct;16(5):722-9. doi: 10.1007/s10157-012-0621-7.

Kuro-o M. Klotho in chronic kidney disease — What`s new? Nephrol Dial Transplant. 2009 Jun;24(6):1705-8. doi: 10.1093/ndt/gfp069.

Wolf M. Update on fibroblast growth factor 23 in chronic kidney disease. Kidney Int. 2012;82(7):737-47. doi: 10.1038/ki.2012.176.



  • There are currently no refbacks.

Copyright (c) 2017 KIDNEYS

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© "Publishing House "Zaslavsky", 1997-2017


 Яндекс.МетрикаSeo анализ сайта Рейтинг