FGF23, Alpha-Klotho and Vitamin D Mediated Calcium-phosphate Metabolism in Haemodialysis Patients

Overview

Journal J Med Biochem

Specialty Biochemistry

Date 2021 Mar 29

PMID 33776565

Citations 2

Authors

Ozge Tugce Pasaoglu

Ayse Senelmis

Ozant Helvaci

Ulver Derici

Hatice Pasaoglu

Affiliations

Soon will be listed here.

Abstract

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

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

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

Conclusions: Our study showed that lack of sufficient amounts of Klotho 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 haemodialysis patients.

Citing Articles

Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus.

Bi J, Zheng M, Li K, Sun S, Zhang Z, Yan N Cardiovasc Diabetol. 2024; 23(1):128.

PMID: 38622690 PMC: 11020347. DOI: 10.1186/s12933-024-02205-2.

Correlation between soluble klotho and chronic kidney disease-mineral and bone disorder in chronic kidney disease: a meta-analysis.

Fan Z, Wei X, Zhu X, Yang K, Tian L, Du Y Sci Rep. 2024; 14(1):4477.

PMID: 38396063 PMC: 10891172. DOI: 10.1038/s41598-024-54812-4.

References

Koh N, Fujimori T, Nishiguchi S, Tamori A, Shiomi S, Nakatani T . Severely reduced production of klotho in human chronic renal failure kidney. Biochem Biophys Res Commun. 2001; 280(4):1015-20. DOI: 10.1006/bbrc.2000.4226. View

Razzaque M, Lanske B . The emerging role of the fibroblast growth factor-23-klotho axis in renal regulation of phosphate homeostasis. J Endocrinol. 2007; 194(1):1-10. PMC: 2900827. DOI: 10.1677/JOE-07-0095. View

Liu Z, Zhou H, Chen X, Chen H, Wang Y, Wang T . Relationship between cFGF23/Klotho ratio and phosphate levels in patients with chronic kidney disease. Int Urol Nephrol. 2019; 51(3):503-507. DOI: 10.1007/s11255-019-02079-4. View

Seiler S, Heine G, Fliser D . Clinical relevance of FGF-23 in chronic kidney disease. Kidney Int Suppl. 2009; (114):S34-42. DOI: 10.1038/ki.2009.405. View

Nitta K, Nagano N, Tsuchiya K . Fibroblast growth factor 23/klotho axis in chronic kidney disease. Nephron Clin Pract. 2014; 128(1-2):1-10. DOI: 10.1159/000365787. View

Lu X, Hu M . Klotho/FGF23 Axis in Chronic Kidney Disease and Cardiovascular Disease. Kidney Dis (Basel). 2017; 3(1):15-23. PMC: 5527179. DOI: 10.1159/000452880. View

Hu M, Shiizaki K, Kuro-O M, Moe O . Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol. 2013; 75:503-33. PMC: 3770142. DOI: 10.1146/annurev-physiol-030212-183727. View

Eddington H, Hoefield R, Sinha S, Chrysochou C, Lane B, Foley R . Serum phosphate and mortality in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2010; 5(12):2251-7. PMC: 2994087. DOI: 10.2215/CJN.00810110. View

Lavi-Moshayoff V, Silver J, Naveh-Many T . Human PTH gene regulation in vivo using transgenic mice. Am J Physiol Renal Physiol. 2009; 297(3):F713-9. DOI: 10.1152/ajprenal.00161.2009. View

10.

Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K . Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006; 444(7120):770-4. DOI: 10.1038/nature05315. View

11.

Shibata K, Fujita S, Morita H, Okamoto Y, Sohmiya K, Hoshiga M . Association between circulating fibroblast growth factor 23, α-Klotho, and the left ventricular ejection fraction and left ventricular mass in cardiology inpatients. PLoS One. 2013; 8(9):e73184. PMC: 3767778. DOI: 10.1371/journal.pone.0073184. View

12.

Kim H, Nam B, Kim D, Kang M, Han J, Lee M . Circulating α-klotho levels in CKD and relationship to progression. Am J Kidney Dis. 2013; 61(6):899-909. DOI: 10.1053/j.ajkd.2013.01.024. View

13.

Seiler S, Wen M, Roth H, Fehrenz M, Flugge F, Herath E . Plasma Klotho is not related to kidney function and does not predict adverse outcome in patients with chronic kidney disease. Kidney Int. 2012; 83(1):121-8. DOI: 10.1038/ki.2012.288. View

14.

Meyer Jr R, Tenenhouse H, Meyer M, Klugerman A . The renal phosphate transport defect in normal mice parabiosed to X-linked hypophosphatemic mice persists after parathyroidectomy. J Bone Miner Res. 1989; 4(4):523-32. DOI: 10.1002/jbmr.5650040411. View

15.

Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt K . Regulation of fibroblast growth factor-23 signaling by klotho. J Biol Chem. 2006; 281(10):6120-3. PMC: 2637204. DOI: 10.1074/jbc.C500457200. View

16.

Isakova T, Wahl P, Vargas G, Gutierrez O, Scialla J, Xie H . Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int. 2011; 79(12):1370-8. PMC: 3134393. DOI: 10.1038/ki.2011.47. View

17.

Moe S, Drueke T . Improving global outcomes in mineral and bone disorders. Clin J Am Soc Nephrol. 2008; 3 Suppl 3:S127-30. PMC: 3152280. DOI: 10.2215/CJN.04331206. View

18.

Kuro-O M . Klotho and endocrine fibroblast growth factors: markers of chronic kidney disease progression and cardiovascular complications?. Nephrol Dial Transplant. 2018; 34(1):15-21. DOI: 10.1093/ndt/gfy126. View

19.

Sakan H, Nakatani K, Asai O, Imura A, Tanaka T, Yoshimoto S . 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. PMC: 3900516. DOI: 10.1371/journal.pone.0086301. View

20.

Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T . Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997; 390(6655):45-51. DOI: 10.1038/36285. View