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

Abstract

BackgroundElevated 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/MethodsWe 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.Results1) 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.ConclusionsHyperphosphatemia 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.

Elevated Phosphate Levels Trigger Autophagy-Mediated Cellular Apoptosis in H9c2 Cardiomyoblasts

“…This result suggests that hyperphosphate in cardiomyocytes triggers excessive apoptosis. In CKD patients, hyperphosphatemia was reported to initiate myocardial damage possibly via apoptosis [16]; interestingly, also in the present study, we proved that hyperphosphate induced apoptosis in H9c2 cells, which might lead to cardiac complications. Furthermore, the autophagy inhibitor (3-MA) showed to inhibit apoptosis significantly, which suggests that the cellular apoptosis is autophagy dependent.…”

“…Inadequate or extreme level of apoptosis would lead to pathological conditions like cancer, Alzheimer disease, ischemia, etc. Recently, hyperphosphate-mediated cellular apoptosis has been reported in human umbilical vein endothelial cells [15] and in CKD patients [16]. However, the molecular pathway mediating apoptosis in cardiomyoblasts is still elusive.…”

Perfil De Pacientes Hemodialíticos Relacionados a Parâmetros Bioquímicos E Hematológicos No Oeste Catarinense

“…Evidenciando-se a presença de anemia, com concentrações reduzidas de hemoglobina e hematócrito, e de alterações em tantos outros parâmetros que direta ou indiretamente geram um aumento crônico do quadro inflamatório e comprometimento imunológico. Para tanto, ressalta-se a necessidade de um monitoramento rigoroso dos parâmetros bioquímicos e hematológicos apresentados pelos pacientes e dos parâmetros que asseguram a qualidade da água utilizada no processo de HD, já que a mesma é um fator independente de biocompatibilidade, e contribui de forma impar para redução da inflamação e correção da anemia 9,21 .…”

Should We Consider the Cardiovascular System While Evaluating CKD-MBD?

“…Moreover, fibrosis interrupts electrical signals, causing the tissue to be more arrhythmogenic [9,23]. Cardio markers and parameters of myocardial function, including Cardiac troponin T (cTnT), left ventricular max index (LVMi), left atrial dimensions (LAD), left ventricular end-systolic dimension (LVDs), left ventricular end-diastolic dimension (LVDd), interventricular septal thickness (IVST), and left ventricular posterior wall thickness (LVPWT), were reported consistently higher in a group of patients with higher serum phosphate (HSP) levels compared to those in the normal serum phosphate group (NSP) group, while left ventricular ejection fraction (LVEF) showed the opposite trend in a CKD cross-sectional study [52]. Furthermore, the lack of difference in mean arterial pressure (MAP) between the two groups suggested that cardiac remodeling including LVH and the declining LVEF might be associated with serum phosphate rather than hypertension and possibly this happens through triggering apoptosis of human cardiomyocytes.…”

“…Phosphate is toxic, impairs endothelial cells, promotes the formation of CPPs, induces VSMC transformation to osteogenic phenotype, and initiates cardiac fibrosis that leads to cardiac remodeling. sectional study [52]. Furthermore, the lack of difference in mean arterial pressure (MAP) between the two groups suggested that cardiac remodeling including LVH and the declining LVEF might be associated with serum phosphate rather than hypertension and possibly this happens through triggering apoptosis of human cardiomyocytes.…”