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

Abstract

Purpose Biggest cause of death in chronic kidney disease-hemodialysis (CKD-HD) patients is cardiovascular disease (CVD). Cardiovascular disease is often associated with mineral bone disorders (MBD), especially vascular and valvular calcification. Biomarkers such as C-terminal-fibroblast growth factor-23 (FGF-23), intact parathyroid hormone (iPTH), and interleukin-6 (IL-6) were investigated. Only few studies have focused on valvular calcification in CKD-HD patients, with controversial results. The present study aimed to investigate whether high C-terminal-FGF-23, iPTH, and IL-6 can be used as determinants of valvular calcification in CKD-MBD patients undergoing regular HD. Patients and Methods This was an analytical cross-sectional study which involved CKD-HD patients aged 18–60 years with no history of CVD, malignancy, and diabetes mellitus. C-terminal FGF-23 was measured using enzyme-linked immunosorbent assay (ELISA) kit, iPTH using chemiluminescent immunometric method, and IL-6 using sandwich enzyme immunoassay technique. Valvular calcification on aortic and mitral valves was examined with echocardiography. Data analysis was done using Chi-squared test or Fisher’s exact test as appropriate and multivariate logistic regression analysis. Results Bivariate analysis with Fisher’s exact test showed significant association of prevalence ratio (PR) of C-terminal FGF-23 (PR = 1.33; p = 0.003; CI (1.017–1.748)), iPTH (PR = 1.361; p = 0.002; CI (1.02–1.816)), and IL-6 (PR = 1.2; p = 0.019; CI (1.000–1.446)) with valvular calcification. Multivariate analysis with logistic regression showed high C-terminal FGF-23 (exp (B) value of 16.44; p = 0.045; CI (1.07–252.75)), iPTH (exp (B) value of 33.312; p = 0.016; CI (1.94–571.71)), and IL-6 (exp (B) value of 21.58; p = 0.0381; CI (1.18–394.87)) were determinants of valvular calcification in CKD-MBD patients undergoing regular HD. Conclusion This study demonstrated that high C-terminal FGF-23, iPTH, and IL-6 were determinants of valvular calcification in CKD-MBD patients undergoing regular HD.

Industrial Use of Phosphate Food Additives: A Mechanism Linking Ultra-Processed Food Intake to Cardiorenal Disease Risk?

“…FGF23 has been shown to have a direct effect on myocardial function, and it has been associated with valvular and vascular calcifications in dialysis patients, as illustrated in Figure 3 . The combination of renal, cardiovascular, and bone effects eventually contributes to increased morbidity and mortality in advanced CKD and dialysis patients [ 66 , 67 , 68 , 69 ]. As documented above, enough data suggest a similar, although more subtle, effect of very high phosphate intake on phosphate metabolism and chronic disease mechanisms in the general population [ 70 ].…”

Supplement of exogenous inorganic pyrophosphate inhibits atheromatous calcification in Apolipoprotein E knockout mice

“…Several reports indicate that inflammation is an important trigger for VC [ 15 , 16 ]. Inflammatory mediators such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ) and interleukin-10 (IL-10) are implied in the pathogenesis of VC [ [17] , [18] , [19] , [20] ]. TNF-α and IFN-γ were reported to enhance the calcification of VSMCs induced by secondary calciprotein particles and IL-6 was shown to increase the transdifferentiation of VSMC into chondrocytes and calcium deposition [ [17] , [18] , [19] , [20] ].…”

“…Inflammatory mediators such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ) and interleukin-10 (IL-10) are implied in the pathogenesis of VC [ [17] , [18] , [19] , [20] ]. TNF-α and IFN-γ were reported to enhance the calcification of VSMCs induced by secondary calciprotein particles and IL-6 was shown to increase the transdifferentiation of VSMC into chondrocytes and calcium deposition [ [17] , [18] , [19] , [20] ]. High level of IL-10 was shown to be involved in the protective effect of IL-37 on VC in apolipoprotein E knockout (ApoE KO) [ 21 ].…”