Original Article

Relationship between Serum Soluble Klotho Protein and Coronary Artery Calcification and Prognosis in Patients on Maintenance Hemodialysis

Abstract

Background: We aimed to investigate the relationship between serum soluble Klotho protein (sKlotho) level and coronary artery calcification (CAC) as well as prognosis in patients with maintenance hemodialysis (MHD).

Methods: Overall, 128 adult patients with end-stage renal failure treated with MHD were collected in the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang Province, China in 2013. Serum sKlotho was detected by ELISA and coronary artery calcification was measured by multi-slice spiral computed tomography (MSCT). With 36 months' follow-up, death notes such as cause of death and death time were recorded.

Results: Patients were divided into low sKlotho group and high sKlotho group. Age, blood phosphorus level, hypertension incidence and incidence of diabetes mellitus of the patients in low sKlotho group was significantly higher than that of high sKlotho group (P<0.05). The coronary artery calcification score (CACs) of patients in high sKlotho group was significantly lower than that of low sKlotho group (P<0.001). Logistic regression showed that the decrease of sKlotho level (P<0.001) was an independent risk factor for CAC progression. The mortality of the patients in low sKlotho group was higher than that of high sKlotho group. Kaplan-Meier survival curve had shown that survival time of the patients in low sKlotho group was significantly lower than that of high sKlotho group (P<0.05).

Conclusion: SKlotho can increase the degree of CAC. Although MHD patients with low sKlotho level had shorter survival time, sKlotho is not an independent risk factor in prediction of prognosis of MHD patients.

 

Kuro-o M, Matsumura Y, Aizawa H et al (1997). Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature, 390(6655): 45-51.

Matsumura Y, Aizawa H, Shiraki-Iida T, Na-gai R, Kuro-o M, Nabeshima Y(1998). Identification of the human klotho gene and its two transcripts encoding mem-brane and secreted klotho protein. Biochem Biophys Res Commun, 242(3): 626-30.

Chen CD, Tung TY, Liang J, Zeldich E, Tucker Zhou TB, Turk BE, Abraham CR (2014). Identification of cleavage sites leading to the shed form of the anti-aging protein klotho. Biochemistry, 53(34): 5579-87.

Kurosu H, Yamamoto M, Clark JD et al (2005). Suppression of aging in mice by the hormone klotho. Science, 309(5742): 1829-33.

Hu MC, Kuro-o M, Moe OW (2013). Renal and extrarenal actions of Klotho. Semin Nephrol, 33(2): 118-29.

Li SA, Watanabe M, Yamada H, Nagai A, Kinuta M, Takei K(2004). Immunohisto-chemical localization of Klotho protein in brain, kidney, and reproductive organs of mice. Cell Struct Funct, 29(4): 91-9.

Koh N, Fujimori T, Nishiguchi S et al (2001). Severely reduced production of klotho in human chronic renal failure kidney. Biochem Biophys Res Commun, 280(4): 1015-20.

Hu MC, Shi M, Zhang J, Quiñones H, Grif-fith C, Kuro-o M, Moe OW(2011). Klotho deficiency causes vascular calcifi-cation in chronic kidney disease. J Am Soc Nephrol, 22(1): 124-36.

Otani-Takei N, Masuda T, Akimoto T et al (2015). Association between serum solu-ble klotho levels and mortality in chronic hemodialysis patients. Int J Endocrinol, 2015: 406269.

Bellasi A, Lacey C, Taylor AJ, Raggi P, Wil-son PW, Budoff MJ, Vaccarino V, Shaw LJ(2007). Comparison of prognostic use-fulness of coronary artery calcium in men versus women (results from a meta- and pooled analysis estimating all-cause mor-tality and coronary heart disease death or myocardial infarction). Am J Cardiol, 100(3): 409-14.

Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R(1990). Quantification of coronary artery calcium using ultrafast computed tomog-raphy. J Am Coll Cardiol, 15(4): 827-32.

Broderick LS, Shemesh J, Wilensky RL et al (1996). Measurement of coronary artery calcium with dual-slice helical CT com-pared with coronary angiography: evalua-tion of CT scoring methods, interob-server variations, and reproducibility. AJR Am J Roentgenol, 167(2): 439-44.

Oh HJ, Nam BY, Lee MJ et al (2015). De-creased Circulating Klotho Levels in Pa-tients Undergoing Dialysis and Relation-ship to Oxidative Stress and Inflamma-tion. Perit Dial Int, 35(1): 43-51.

Hum JM, O'Bryan LM, Tatiparthi AK et al (2017). Chronic hyperphosphatemia and vascular calcification are reduced by stable delivery of soluble Klotho. J Am Soc Nephrol, 28(4): 1162-74.

Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, Miyamoto K, Fuku-shima N(2003). Human fibroblast growth factor⁃23 mutants suppress Na+ ⁃dependent phosphate co-transport ac-tivity and 1alpha,25⁃dihydroxyvitamin D3 production. J Biol Chem, 278(4): 2206-11.

Gao D, Zuo Z, Tian J, Ali Q, Lin Y, Lei H, Sun Z(2016). Activation of SIRT1 Atten-uates Klotho Deficiency-Induced Arterial Stiffness and Hypertension by Enhanc-ing AMP-Activated Protein Kinase Activi-ty. Hypertension, 68(5): 1191-9.

Ikushima M, Rakugi H, Ishikawa K, Maeka-wa Y, Yamamoto K, Ohta J, Chihara Y, Kida I, Ogihara T(2006). Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells. Biochem Biophys Res Commun, 339(3): 827-32.

Utsugi T, Ohno T, Ohyama Y et al (2000). Decreased insulin production and in-creased inshulin sensitivity in the klotho mutant mouse, a novel animal model for human aging. Metabolism, 49(9): 1118-23.

Nie F, Wu D, Du H, Yang X, Yang M, Pang X, Xu Y(2016). Serum Klotho protein levels and their correlations with the pro-gression of type 2 diabetes mellitus. J Di-abetes Complications, 31(3): 594-8.

Semba RD, Cappola AR, Sun K, Bandinelli S, Dalal M, Crasto C, Guralnik JM, Fer-rucci L(2011). Plasma Klotho and cardio-vascular disease in adults. J Am Geriatr Soc, 59(9): 1596-601.

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IssueVol 47 No 4 (2018) QRcode
SectionOriginal Article(s)
Keywords
Kidney dialysis Soluble Klotho protein Coronary artery calcification Mortality

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How to Cite
1.
ZHENG S, ZHENG Y, JIN L, ZHOU Z, LI Z. Relationship between Serum Soluble Klotho Protein and Coronary Artery Calcification and Prognosis in Patients on Maintenance Hemodialysis. Iran J Public Health. 2018;47(4):510-518.