Ruchi Singh, Sudha P Chennasamudram, Sudip Sheth and Tetyana L Vasylyeva
Objective: This study was design to evaluate the correlation between FGF-23 and other cardiovascular risk factors (markers of endothelial dysfunction and inflammation) in ESRD patients with T2DM on PD.
Method: Sixty serum samples collected (four times, at weeks 0, 8, 10, and 18) from 15 patients with Type 2 Diabetes (T2DM) and ESRD on PD were analysed to study the relationship between the levels of FGF-23 and markers of endothelial dysfunction and inflammation. ELISA kits were used to quantitate Endothelin-1 (ET-1), soluble vascular adhesion molecule, Plasminogen Activator Inhibitor-1 (PAI-1), FGF-23, C-reactive protein, Interleukin-6 (IL-6), Tumor Necrosis Factor Alpha (TNF-α) and cluster of differentiation 146 (CD 146). The association between FGF-23, mineral metabolites, and markers of inflammation were analyzed using Spearman correlations. Linear regression models were used to examine the univariate and multivariate adjusted associations between FGF-23 as primary exposure and individual inflammatory markers [including IL-6, PAI-1 and CD146] as the dependent variables. Multivariate analyses were adjusted for factors associated with mineral metabolism such as serum phosphate, Ca×PO4 product, and LDL concentration. Two-sided p values<0.05 were considered statistically significant.
Result: FGF-23 was positively correlated with phosphate (r=0.57; p<0.0001) and Ca×PO4 product (r=0.61; p<0.0001). FGF-23 showed the strongest correlation with IL-6 (r=0.32; p<0.05), PAI-1 (r=0.21; p<0.05) and CD 146 (r=0.29; p<0.05). In univariate and multivariate regression analysis, FGF-23 was significantly associated with IL-6, PAI-1, and CD 146. These results were qualitatively unchanged in the model that was further adjusted for Ca×PO4 product, serum phosphate, and LDL.
Conclusion: Our results indicate that FGF-23 impacts the cardiovascular health of T2DM patients on PD through mechanisms, which are independent from phosphate levels and linked directly to inflammation and endothelial dysfunction.