Association between ratio of fibroblast growth factor 23 (FGF-23) to klotho and phosphate level in chronic kidney disease patient
Keywords:
FGF-23, Klotho, FGF23-Klotho ratio, phosphate, Chronic Kidney DiseaseAbstract
Background and aim: Chronic Kidney Disease (CKD) is a condition in which there is structural and functional damage to the kidneys that lasts more than 3 months, and when there is a decrease in glomerular filtration rate (GFR), phosphate homeostasis is disrupted. FGF-23 acts as a phosphaturic hormone that increases phosphate excretion when there is an increase in serum phosphate levels. The physiological effects of FGF-23 can occur when it binds to Klotho as a co-receptor, where Klotho is mainly produced in the kidneys. Decreased kidney function triggers a decrease in kidney mass, so that Klotho production will decrease. This study aimed to determine the association between the ratio of FGF-23 to Klotho and phosphate levels in patients with CKD. Methods: This was an observational study involving 60 patients with stage 3, 4, and 5 non-dialysis CKD. Serum of FGF-23, Klotho, phosphate, and creatinine were measured using the ELISA method. Statistical analysis was performed using Mann-Whitney, Chi-Square, and Spearman Correlation Tests. Results: The median value of FGF23-Klotho ratio was 0.17. A significant correlation was found between the FGF23-Klotho ratio and phosphate levels (P<0.001, r= 0.581). There was a significant relationship between the female sex and the incidence of hyperphosphatemia (P=0.0038). Conclusion: The higher the FGF23-Klotho ratio, the higher the phosphate levels in CKD patients and it can be a risk factor, protective factor, and for diagnostic, therapeutic and prognostic purposes in assessing phosphate levels and hyperphosphatemia conditions in CKD patients.
References
Levin A, Stevens PE, Bilous RW, et al. Kidney disease: Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3(1):1–150. doi: 10.1038/kisup.2012.73
Moe SM. Disorders Involving Calcium, Phosphorus, and Magnesium. Prim Care - Clin Off Pract. 2008;35(2):118–28. doi: 10.1016/j.pop.2008.01.007
Fourtounas C. Phosphorus metabolism in chronic kidney disease. Hippokratia. 2011;15:50–2.
Kritmetapak K, Losbanos L, Berent TE, et al. Hyperphosphatemia with elevated serum PTH and FGF23, reduced 1,25(OH)2D and normal FGF7 concentrations characterize patients with CKD. BMC Nephrol. 2021;22(1):21–8. doi: 10.1186/s12882-021-02311-3
Liu Z, Zhou H, Chen X, et al. Relationship between cFGF23/Klotho ratio and phosphate levels in patients with chronic kidney disease. Int Urol Nephrol. 2019;51(3):503–7. doi: 10.1007/s11255-019-02079-4
Gutierrez O, Isakova T, Rhee E, et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol. 2005;16(7):2205–15. doi: 10.1681/ASN.2005010052
Isakova T, Wahl P, Vargas GS, 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
Zhou C, Shi Z, Ouyang N, Ruan X. Hyperphosphatemia and Cardiovascular Disease. Front Cell Dev Biol. 2021;9:1–11. doi: 10.3389/fcell.2021.644363
Hruska KA, Seifert M, Sugatani T. Pathophysiology of the chronic kidney disease - Mineral bone disorder. Curr Opin Nephrol Hypertens. 2015;24(4):303–9. doi: 10.1097/MNH.0000000000000132
Lederer E. Regulation of serum phosphate. J Physiol. 2014;592(18):3985–95. doi: 10.1113/jphysiol.2014.273979
Hu X, Ma X, Luo Y, et al. Associations of serum fibroblast growth factor 23 levels with obesity and visceral fat accumulation. Clin Nutr. 2018;37(1):223–8. doi: 10.1016/j.clnu.2016.12.010
Titan SM, Zatz R, Graciolli FG, et al. FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin J Am Soc Nephrol. 2011;6(2):241–7. doi: 10.2215/CJN.04250510
Zou D, Wu W, He Y, Ma S, Gao J. The role of klotho in chronic kidney disease. BMC Nephrol. 2018;19(1):1–12. doi: 10.1186/s12882-018-1094-z
Rotondi S, Pasquali M, Tartaglione L, et al. Soluble α -Klotho serum levels in chronic kidney disease. Int J Endocrinol. 2015;1–8. doi: 10.1155/2015/872193
Caravaca F, Villa J, García de Vinuesa E, et al. Asociación entre fósforo sérico y progresión de la enfermedad renal crónica avanzada. Nefrologia. 2011;31(6):707–15. doi: 10.3265/Nefrologia.pre2011.Sep.11089
Canziani MEF, Tomiyama C, Higa A, Draibe SA, Carvalho AB. Fibroblast growth factor 23 in chronic kidney disease: Bridging the gap between bone mineral metabolism and Left Ventricular Hypertrophy. Blood Purif. 2011;31(1–3):26–32. doi: 10.1159/000321368
Faul C, Amaral AP, Oskouei B, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011;121(11):4393–408. doi: 10.1172/JCI46122
Mirza MAI, Larsson A, Melhus H, Lind L, Larsson TE. Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population. Atherosclerosis. 2009;207(2):546–51. doi: 10.1016/j.atherosclerosis.2009.05.013
Shibata K, Fujita S ichi, Morita H, et al. 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):3184. doi: 10.1371/journal.pone.0073184
Marsell R, Grundberg E, Krajisnik T, et al. Fibroblast growth factor-23 is associated with parathyroid hormone and renal function in a population-based cohort of elderly men. Eur J Endocrinol. 2008;158(1):125–9. doi: 10.1530/EJE-07-0534
Fliser D, Kollerits B, Neyer U, et al. Fibroblast Growth Factor 23 (FGF23) predicts progression of chronic kidney disease: The Mild to Moderate Kidney Disease (MMKD) study. J Am Soc Nephrol. 2007;18(9):2601–8. doi: 10.1681/ASN.2006080936
Pavik I, Jaeger P, Ebner L, et al. Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: A sequence suggested from a cross-sectional study. Nephrol Dial Transplant. 2013;28(2):352–9. doi: 10.1093/ndt/gfs460
Kim HR, Nam BY, Kim DW, et al. 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
Shimamura Y, Hamada K, Inoue K, et al. Serum levels of soluble secreted a-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis. Clin Exp Nephrol. 2012;16(5):722–9. doi: 10.1007/s10157-012-0621-7
Seiler S, Wen M, Roth HJ, et al. Plasma Klotho is not related to kidney function and does not predict adverse outcome in patients with chronic kidney disease. Kidney Int. 2013;83(1):121–8. doi: 10.1038/ki.2012.288
Tabibzadeh N, Mentaverri R, Daroux M, et al. Differential Determinants of Tubular Phosphate Reabsorption: Insights on Renal Excretion of Phosphates in Kidney Disease. Am J Nephrol. 2018;47(5):300–3. doi: 10.1159/000488864
Disthabanchong S. Phosphate and Cardiovascular Disease beyond Chronic Kidney Disease and Vascular Calcification. Int J Nephrol. 2018 Apr 8;2018:3162806. doi: 10.1155/2018/3162806.
Nadin C. Sevelamer as a phosphate binder in adult hemodialysis patients: An evidence-based review of its therapeutic value. Core Evid. 2005;1(1):43–63.
Abdallah E, Mosbah O, Khalifa G, Metwaly A, El-Bendary O. Assessment of the relationship between serum soluble Klotho and carotid intima-media thickness and left ventricular dysfunction in hemodialysis patients. Kidney Res Clin Pract. 2016;35(1):42–9. doi: 10.1016/j.krcp.2015.12.006
Apostolović B, Cvetković T, Stefanović N, et al. The predictive value of Klotho polymorphism, in addition to classical markers of CKD-MBD, for left ventricular hypertrophy in haemodialysis patients. Int Urol Nephrol. 2019;51(8):1425–33. doi: 10.1007/s11255-019-02193-3
Tanaka S, Fujita S, Kizawa S, Morita H, Ishizaka N. Association between FGF23, α-Klotho, and Cardiac Abnormalities among Patients with Various Chronic Kidney Disease Stages. PLoS One. 2016 Jul 11;11(7):e0156860. doi: 10.1371/journal.pone.0156860.
Semba RD, Cappola AR, Sun K, et al. Plasma klotho and cardiovascular disease in adults. J Am Geriatr Soc. 2011;59(9):1596–601. doi: 10.1111/j.1532-5415.2011.03558.x
Seifert ME, De Las Fuentes L, Ginsberg C, et al. Left ventricular mass progression despite stable blood pressure and kidney function in stage 3 chronic kidney disease. Am J Nephrol. 2014;39(5):392–9. doi: 10.1159/000362251
Yang K, Wang C, Nie L, et al. Klotho protects against indoxyl sulphate-induced myocardial hypertrophy. J Am Soc Nephrol. 2015;26(10):2434–46. doi: 10.1681/ASN.2014060543
Cha SK, Ortega B, Kurosu H, Rosenblatt KP, Kuro-o M, Huang CL. Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1. Proc Natl Acad Sci U S A. 2008;105(28):9805–10. doi: 10.1073/pnas.0803223105
Hu MC, Shi M, Zhang J, et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2011;22(1):124–36. doi: 10.1681/ASN.2009121311
Wojcicki JM. Hyperphosphatemia is associated with anemia in adults without chronic kidney disease: Results from the National Health and Nutrition Examination Survey (NHANES): 2005-2010. BMC Nephrol. 2013;14(1):178–90. doi: 10.1186/1471-2369-14-178
Rabbani SA, S. SB, Rao PG, Kurian MT, Essawy B El. Hyperphosphatemia In End Stage Renal Disease: Prevalence And Patients Characteristics Of Multiethnic Population Of United Arab Emirates. Int J Pharm Pharm Sci. 2017;9(12):283. doi: 10.22159/ijpps.2017v9i12.22425
Bellasi A, Mandreoli M, Baldrati L, et al. Chronic kidney disease progression and outcome according to serum phosphorus in mild-to-moderate kidney dysfunction. Clin J Am Soc Nephrol. 2011;6(4):883–91. doi: 10.2215/CJN.07810910
Uemura H, Irahara M, Yoneda N, et al. Close correlation between estrogen treatment and renal phosphate reabsorption capacity. J Clin Endocrinol Metab. 2000;85(3):1215–9. doi: 10.1210/jcem.85.3.6456
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Irham Khairi, Hasyim Kasim, Syakib Bakri, Luthfi Parewangi, Husaini Umar, Arifin Seweng
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.
How to Cite
