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25 October 2014 : Original article  

Elevated Cardiac Markers in Chronic Kidney Disease as a Consequence of Hyperphosphatemia-Induced Cardiac Myocyte Injury

Shu WangABCDEFG, Ling QinBDG, Tianfu WuDEF, Bingqing DengACG, Yuerun SunBE, Dayong HuBC, Chandra MohanAF, Xin J. ZhouCD, Ai PengADG

DOI: 10.12659/MSM.890909

Med Sci Monit 2014; 20:2043-2053

Abstract

BACKGROUND: Elevated cardiac markers (CMs) and hyperphosphatemia are commonly encountered in patients with chronic kidney diseases (CKD), but the causal relationship between them has not been established.

MATERIAL AND METHODS: We enrolled 151 patients with different kidney functions in a cross-sectional study to explore the relationship of serum phosphorus with CMs, including cardiac troponin T (cTnT), myoglobin (MYO), creatine kinase-MB (CK-MB), and brain natriuretic peptide (BNP). Then, the effect of reducing phosphorus levels on CMs by taking phosphate binder for 3 months was prospectively observed in 64 hemodialysis patients. Finally, human cardiomyocytes were exposed to different concentrations of inorganic phosphorus to examine its underlying mechanism.

RESULTS: 1) Serum phosphorus and CMs gradually increased as the glomerular filtration rate declined in CKD patients (p<0.01). 2) Elevation of CMs was much greater and cardiac structure and function were worse in CKD patients who had higher serum phosphorus concentrations (p<0.05). 3) Serum phosphorus level positively correlated with cTnT, MYO, and BNP in CKD patients (p<0.001). 4) In hemodialysis patients, the reduction of cTnT, MYO, and CK-MB was synchronous with the pharmacologically-induced decline of serum phosphorus level. However, levels of serum Fibroblast growth factor 23 (FGF23) had no statistical decrease. 5) Simulated hyperphosphatemia inhibited proliferation of human cardiomyocytes in a time- and concentration-dependent manner.

CONCLUSIONS: Hyperphosphatemia may induce myocardial damage in CKD patients, possibly through triggering apoptosis of human cardiomyocytes, and this could account for the elevated cardiac markers in CKD patients.

Keywords: Heart Diseases - metabolism, Glomerular Filtration Rate, Biological Markers - metabolism, Hyperphosphatemia - metabolism, Kidney Failure, Chronic - physiopathology, Myocytes, Cardiac - pathology

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750