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

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.