Dual Roles of the Mineral Metabolism Disorders Biomarkers in Prevalent Hemodilysis Patients: In Renal Bone Disease and in Vascular Calcification

Overview

Journal J Med Biochem

Specialty Biochemistry

Date 2019 Mar 15

PMID 30867641

Citations 10

Authors

Marko Baralic

Voin Brkovic

Vesna Stojanov

Sanja Stankovic

Natasa Lalic

Petar duric

Ljubica dukanovic

Milorad Kasikovic

Milan Petrovic

Marko Petrovic

Milan Stosovic

Visnja Lezaic

Affiliations

Soon will be listed here.

Abstract

Background: Vascular calcification (VC) is highly prevalent in dialysis (HD) patients, and its mechanism is multifactorial. Most likely that systemic or local inhibitory factor is overwhelmed by promoters of VC in these patients. VC increased arterial stiffness, and left ventricular hypertrophy. Thus, the present study aimed to investigate the association of VC and myocardial remodeling and to analyze their relationship with VC promoters (fibroblast growth factor 23-FGF23, Klotho, intact parathormon-iPTH, vitamin D) in 56 prevalent HD patients (median values: age 54 yrs, HD vintage 82 months).

Methods: Besides routine laboratory analyzes, serum levels of FGF 23, soluble Klotho, iPTH, 1,25-dihydroxyvitamin D3; pulse wave velocity (PWV); left ventricular (LV) mass by ultrasound; and VCs score by Adragao method were measured.

Results: VC was found in 60% and LV concentric or eccentric hypertrophy in 50% patients. Dialysis vintage (OR 1.025, 95%CI 1.007-1.044, p=0.006) FGF23 (OR 1.006, 95% CI 0.992-1.012, p=0.029) and serum magnesium (OR 0.000, 95%CI 0.000-0.214, p=0.04) were associated with VC. Changes in myocardial geometry was associated with male sex (beta=-0.273, 95% CI -23.967 1.513, p=0.027), iPTH (beta 0.029, 95%CI -0.059-0.001, p=0.027) and vitamin D treatment (beta 25.49, 95%CI 11.325-39.667, p=0.001). Also, patients with the more widespread VC had the highest LV remodeling categories. PWV was associated patient's age, cholesterol, diastolic blood pressure, LV mass (positively) and serum calcium (negatively), indicating potential link with atherosclerotic risk.

Conclusions: Despite to different risk factors for VC and myocardial remodeling, obtained results could indicate that risk factors intertwine in long-term treatment of HD patients and therefore careful and continuous correction of mineral metabolism disorders is undoubtedly of the utmost importance.

Citing Articles

Comparative Analysis of Vascular Calcification Risk Factors in Pre-Hemodialysis and Prevalent Hemodialysis Adult Patients: Insights into Calcification Biomarker Associations and Implications for Intervention Strategies in Chronic Kidney Disease.

Petrovic M, Brkovic V, Baralic M, Maric I, Petkovic N, Stankovic S Diagnostics (Basel). 2024; 14(8).

PMID: 38667470 PMC: 11049133. DOI: 10.3390/diagnostics14080824.

Role of klotho and fibroblast growth factor 23 in arterial calcification, thickness, and stiffness: a meta-analysis of observational studies.

Kencono Wungu C, Susilo H, Alsagaff M, Witarto B, Witarto A, Pakpahan C Sci Rep. 2024; 14(1):5712.

PMID: 38459119 PMC: 10923819. DOI: 10.1038/s41598-024-56377-8.

Serum Intact Fibroblast Growth Factor 23 Levels Are Negatively Associated with Bone Mineral Density in Chronic Hemodialysis Patients.

Lee W, Fang Y, Chen M, Liou H, Lee C, Tsai M J Clin Med. 2023; 12(4).

PMID: 36836085 PMC: 9964480. DOI: 10.3390/jcm12041550.

The controversy of klotho as a potential biomarker in chronic kidney disease.

Yu L, Li S, Sha M, Kong J, Ye J, Liu Q Front Pharmacol. 2022; 13:931746.

PMID: 36210812 PMC: 9532967. DOI: 10.3389/fphar.2022.931746.

High C-Terminal Fibroblast Growth Factor-23, Intact Parathyroid Hormone, and Interleukin-6 as Determinants of Valvular Calcification in Regular Hemodialysis Patients.

Kandarini Y, Mahadita G, Herawati S, Wibhuti I, Widiana I, Ayu N Int J Gen Med. 2022; 15:4227-4236.

PMID: 35480992 PMC: 9035456. DOI: 10.2147/IJGM.S359168.

References

London G, Guerin A, Marchais S, Metivier F, Pannier B, Adda H . Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003; 18(9):1731-40. DOI: 10.1093/ndt/gfg414. View

Adragao T, Pires A, Lucas C, Birne R, Magalhaes L, Goncalves M . A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients. Nephrol Dial Transplant. 2004; 19(6):1480-8. DOI: 10.1093/ndt/gfh217. View

Nitta K, Akiba T, Uchida K, Otsubo S, Otsubo Y, Takei T . Left ventricular hypertrophy is associated with arterial stiffness and vascular calcification in hemodialysis patients. Hypertens Res. 2004; 27(1):47-52. DOI: 10.1291/hypres.27.47. View

London G, Marty C, Marchais S, Guerin A, Metivier F, de Vernejoul M . Arterial calcifications and bone histomorphometry in end-stage renal disease. J Am Soc Nephrol. 2004; 15(7):1943-51. DOI: 10.1097/01.asn.0000129337.50739.48. View

Ikushima M, Rakugi H, Ishikawa K, Maekawa Y, Yamamoto K, Ohta J . Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells. Biochem Biophys Res Commun. 2005; 339(3):827-32. DOI: 10.1016/j.bbrc.2005.11.094. View

Raggi P, Bellasi A, Ferramosca E, Islam T, Muntner P, Block G . Association of pulse wave velocity with vascular and valvular calcification in hemodialysis patients. Kidney Int. 2007; 71(8):802-7. DOI: 10.1038/sj.ki.5002164. View

Yamada K, Fujimoto S, Nishiura R, Komatsu H, Tatsumoto M, Sato Y . Risk factors of the progression of abdominal aortic calcification in patients on chronic haemodialysis. Nephrol Dial Transplant. 2007; 22(7):2032-7. DOI: 10.1093/ndt/gfm031. View

Liu S, Quarles L . How fibroblast growth factor 23 works. J Am Soc Nephrol. 2007; 18(6):1637-47. DOI: 10.1681/ASN.2007010068. View

Kawata T, Imanishi Y, Kobayashi K, Miki T, Arnold A, Inaba M . Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism. J Am Soc Nephrol. 2007; 18(10):2683-8. DOI: 10.1681/ASN.2006070783. View

10.

Fujii H, Kim J, Abe T, Umezu M, Fukagawa M . Relationship between parathyroid hormone and cardiac abnormalities in chronic dialysis patients. Intern Med. 2007; 46(18):1507-12. DOI: 10.2169/internalmedicine.46.0269. View

11.

Gutierrez O, Mannstadt M, Isakova T, Rauh-Hain J, Tamez H, Shah A . Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008; 359(6):584-92. PMC: 2890264. DOI: 10.1056/NEJMoa0706130. View

12.

Adragao T, Pires A, Birne R, Dias Curto J, Lucas C, Goncalves M . A plain X-ray vascular calcification score is associated with arterial stiffness and mortality in dialysis patients. Nephrol Dial Transplant. 2008; 24(3):997-1002. DOI: 10.1093/ndt/gfn584. View

13.

Giachelli C . The emerging role of phosphate in vascular calcification. Kidney Int. 2009; 75(9):890-7. PMC: 2807740. DOI: 10.1038/ki.2008.644. View

14.

Kanbay M, Goldsmith D, Akcay A, Covic A . Phosphate - the silent stealthy cardiorenal culprit in all stages of chronic kidney disease: a systematic review. Blood Purif. 2009; 27(2):220-30. DOI: 10.1159/000197562. View

15.

Jean G, Terrat J, Vanel T, Hurot J, Lorriaux C, Mayor B . High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients. Nephrol Dial Transplant. 2009; 24(9):2792-6. DOI: 10.1093/ndt/gfp191. View

16.

. 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. DOI: 10.1038/ki.2009.188. View

17.

NasrAllah M, El-Shehaby A, Salem M, Osman N, El Sheikh E, Sharaf El Din U . Fibroblast growth factor-23 (FGF-23) is independently correlated to aortic calcification in haemodialysis patients. Nephrol Dial Transplant. 2010; 25(8):2679-85. DOI: 10.1093/ndt/gfq089. View

18.

. Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: 'establishing normal and reference values'. Eur Heart J. 2010; 31(19):2338-50. PMC: 2948201. DOI: 10.1093/eurheartj/ehq165. View

19.

Ketteler M, Rothe H, Kruger T, Biggar P, Schlieper G . Mechanisms and treatment of extraosseous calcification in chronic kidney disease. Nat Rev Nephrol. 2011; 7(9):509-16. DOI: 10.1038/nrneph.2011.91. View

20.

Faul C, Amaral A, Oskouei B, Hu M, Sloan A, Isakova T . FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011; 121(11):4393-408. PMC: 3204831. DOI: 10.1172/JCI46122. View