Top

European Journal of Medical Research

Published in:

Open Access 01-12-2018 | Research

Correlation of serum levels of fibroblast growth factor 23 and Klotho protein levels with bone mineral density in maintenance hemodialysis patients

Authors: Shubei Zheng, Yan Chen, Yu Zheng, Zhihong Zhou, Zhanyuan Li

Published in: European Journal of Medical Research | Issue 1/2018

Abstract

Objective

The correlation of serum fibroblast growth factor 23 (FGF-23) and Klotho protein levels with bone mineral density (BMD) in maintenance hemodialysis (MHD) patients was analyzed.

Methods

Between January 2015 and November 2015, 125 MHD patients in our hospital were enrolled. Dual-energy X-ray absorptiometry was used to examine the BMD in the femoral neck and lumbar spine of MHD patients. The patients were divided into three groups: a normal bone mass group, an osteopenia group, and an osteoporosis group. An ELISA was performed to measure serum FGF-23, Klotho protein, and 1,25(OH)₂VitD₃ levels. Other parameters, including calcium (Ca), phosphorus (P), and parathyroid hormone, were also measured.

Results

Of the 125 MHD patients, 82.40% of patients had femoral neck osteopenia, and 56.00% of patients had lumbar spinal osteopenia. The serum FGF-23 level was highest in the osteoporosis group. However, there was no significant difference in serum FGF-23 levels among the three groups, depending on femoral neck and lumbar spinal BMD (P > 0.05). Spearman’s correlation analysis also pointed to a lack of correlation between serum FGF-23 levels and BMD. Among the three groups, there were significant differences in serum Klotho protein levels and femoral neck BMD (P < 0.05). Serum Klotho protein levels in the osteoporosis group were clearly lower than those in the normal bone mass group and osteopenia group (P < 0.05). Similarly, serum Klotho protein levels were significantly lower in those with lumbar spinal osteopenia as compared with those in the normal group. There was a positive correlation between serum Klotho protein levels and BMD and T values for the femoral neck and lumbar spine. The results of a multiple linear regression analysis revealed that the serum Klotho protein level was one of the main factors affecting BMD in MHD patients.

Conclusions

The serum level of FGF-23 was not correlated with a change in BMD of MHD patients, whereas the serum Klotho protein level was associated with the degree of BMD. A high Klotho protein level may decrease the severity of chronic kidney disease and mineral bone disorder (CKD-MBD) in MHD patients with low BMD.

Qureshi R, Dhrolia MF, Nasir K, et al. Comparison of total direct cost of conventional single use and mechanical reuse of dialyzers in patients of end-stage renal disease on maintenance hemodialysis: a single center study. Saudi J Kidney Dis Transp. 2016;27:774–80.CrossRef

Markaki A, Gkouskou K, Stylianou K, et al. Relationship between adiposity, adipokines, inflammatory markers and lipid profile in hemodialysis patients. Eur Rev Med Pharmacol Sci. 2014;18:1496–8.PubMed

Group KDIGOC-MW. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009;113:S1–130.

Carrillo-López N, Panizo S, Alonso-Montes C, et al. Direct inhibition of osteoblastic Wnt pathway byfibroblast growth factor 23 contributes to bone loss in chronic kidney disease. Kidney Int. 2016;90:77–89.CrossRefPubMed

Gattineni J, Alphonse P, Zhang Q, et al. Regulation of renal phosphate transport by FGF23 is mediated by FGFR1 and FGFR4. Am J Physiol Renal Physiol. 2014;306:F351–8.CrossRefPubMed

Lavi MV, Wasserman G, Meir T, et al. PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. Am J Physiol Renal Physiol. 2010;299:F882–9.CrossRef

Prasad N, Jaiswal A, Agarwal V, et al. FGF23 is associated with early post-transplant hypophosphataemia and normalizes faster than iPTH in living donor renal transplant recipients: a longitudinal follow-up study. Clin Kidney J. 2016;9:669–76.CrossRefPubMedPubMedCentral

Shigematsu T, Kazama JJ, Yamashita T, et al. Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis. 2004;44:250–6.CrossRefPubMed

Krieger NS, Culbertson CD, Kykersnowman K, Bushinsky DA. Metabolic acidosis increases fibroblast growth factor 23 in neonatal mouse bone. Am J Physiol Renel Physiol. 2012;303:F431–6.CrossRef

10.

Guo Y, Sun N, Duan X, et al. Estrogen deficiency leads to further bone loss in the mandible of CKD mice. PLoS ONE. 2016;11:e0148804.CrossRefPubMedPubMedCentral

11.

Carrillo-López N, Román-García P, Rodríguez-Rebollar A, et al. Indirect regulation of PTH by estrogens may require FGF23. J Am Soc Nephrol. 2009;20:2009–17.CrossRefPubMedPubMedCentral

12.

Lane NE, Parimi N, Corr M, et al. Association of serum fibroblast growth factor 23 (FGF23) and incident fractures in older men: the osteoporotic fractures in men (MrOS) study. J Bone Miner Res. 2013;28:2325–32.CrossRefPubMedPubMedCentral

13.

Wang H, Yoshiko Y, Yamamoto R, et al. Overexpression of fibroblast growth factor 23 suppresses osteoblast differentiation and matrix mineralization in vitro. J Bone Miner Res. 2008;23:939–48.CrossRefPubMed

14.

Urena Torres P, Friedlander G, de Vernejoul MC, et al. Bone mass does not correlate with the serum fibroblast growth factor 23 in hemodialysis patients. Kidney Int. 2008;73:102–7.CrossRefPubMed

15.

Coskun Y, Paydas S, Balal M, et al. Bone disease and serum fibroblast growth factor-23 levels in renal transplant recipients. Transplant Proc. 2016;48:2040–5.CrossRefPubMed

16.

Fukumoto S. FGF23-FGF receptor/Klotho pathway as a new drug target for disorders of bone and mineral metabolism. Calcif Tissue Int. 2016;98:334–40.CrossRefPubMed

17.

Koh N, Fujimori T, Nishiguchi S, et al. Severely reduced production of klotho in human chronic renal failure kidney. Biochem Biophys Res Commun. 2001;280:1015–20.CrossRefPubMed

18.

Kuro-O M. Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism. Curr Opin Nephrol Hypertens. 2006;15:437–41.CrossRefPubMed

19.

Maruyama N, Shibata Y, Mochizuki A, et al. Bone micro-fragility caused by the mimetic aging processes in α-klotho deficient mice: in situ nanoindentation assessment of dilatational bands. Biomaterials. 2015;47:62–71.CrossRefPubMed

20.

Nabeshima Y. Regulation of calcium homeostasis by α-Klotho and FGF23. Clin Calcium. 2010;20:1677–85.PubMed

21.

Wolf MT, An SW, Nie M, et al. Klotho up-regulates renal calcium channel transient receptor potential vanilloid 5 (TRPV5) by intra- and extracellular N-glycosylation-dependent mechanisms. J Biol Chem. 2014;289:35849–57.CrossRefPubMedPubMedCentral

22.

Olauson H, Lindberg K, Amin R, et al. Parathyroid-specific deletion of klotho unravels a novel calcineurin-dependent FGF23 signaling pathway that regulates PTH secretion. PLoS Genet. 2013;9:e1003975.CrossRefPubMedPubMedCentral

23.

Maeda R, Imura A, Nabeshima Y. Complex regulation and diverse functions of alpha-Klotho. Contrib Nephrol. 2013;180:25–46.CrossRefPubMed

24.

Kurz DJ, Decary S, Hong Y, et al. Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells. J Cell Sci. 2004;117:2417–26.CrossRefPubMed

Title: Correlation of serum levels of fibroblast growth factor 23 and Klotho protein levels with bone mineral density in maintenance hemodialysis patients
Authors: Shubei Zheng
Yan Chen
Yu Zheng
Zhihong Zhou
Zhanyuan Li
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: European Journal of Medical Research / Issue 1/2018
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/s40001-018-0315-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Correlation of serum levels of fibroblast growth factor 23 and Klotho protein levels with bone mineral density in maintenance hemodialysis patients

Abstract

Objective

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2018

Transcatheter aortic valve implantation with a mechanically expandable prosthesis: a learning experience for permanent pacemaker implantation rate reduction

Clinical effect of selective interventional therapy on sub-acute ST-segment elevation myocardial infarction under the guidance of fractional flow reserve and coronary arteriography

Association of serum ADAMTS-7 levels with left ventricular reverse remodeling after ST-elevation myocardial infarction

Treatment of onychomycosis using a 1064-nm diode laser with or without topical antifungal therapy: a single-center, retrospective analysis in 56 patients

Correlation analysis on serum inflammatory cytokine level and neurogenic pulmonary edema for children with severe hand–foot–mouth disease

Non-linear optical microscopy and histological analysis of collagen, elastin and lysyl oxidase expression in breast capsular contracture