#5566 DIETARY MAGNESIUM SUPPLEMENTATION REDUCES RENAL AND CARDIAC FIBROSIS IN AN EXPERIMENTAL MODEL OF TYPE 4 CARDIORENAL SYNDROME

Abstract

Abstract Background and Aims In chronic kidney disease (CKD) patients, high serum phosphate (HP) levels are associated with the development of a cardiorenal renal syndrome type 4 (CRS4). In this syndrome, the heart is damaged by oxidative stress, inflammation, and fibrosis in renal tissue. In this study we have evaluated if dietary Mg supplementation could reduce CRS4. Method The in vivo studies were performed in 5/6Nx rats fed a high (0.9%) phosphate diet with high or low dietary content of Mg to evaluate: 1) The effect of dietary Mg supplementation (0.3%) on oxidative stress, inflammation and fibrosis of kidney and heart. 2) The contribution of hypomagnesemia (using a low Mg diet (0,03%) to the progression of CRS4 in Nx rats and normal rats as controls. 3) Whether dietary Mg supplementation (8 weeks) reduces renal and cardiac fibrosis in Nx rats with established CRS4. In vitro, we evaluated the effects of Mg (Mg2Cl) on mesangial and tubular cells and also cardiomyocytes cells expose to TGF-β. Results Dietary Mg supplementation (0,3%) improved renal function, decreased oxidative stress, FGF23 levels, hypertension, renal and cardiac fibrosis and recovered renal expression of Klotho. A low Mg diet increased FGF23 and renal fibrosis but a subsequent switch to dietary Mg supplementation did not significantly improve CRS4 parameters although it reduced the values of blood pressure. In HK2 and rat mesangial cells treated with TGFβ (100 ng/ml), high Mg levels (1,4- and 2,8-times basal levels in the medium) reduced the amount of pro-fibrotic proteins such as α-smooth muscle actin, fibronectin, or renin, recovering Klotho expression and decreasing Smad3 phosphorylation. Conclusion Dietary Mg supplementation is a useful tool to improve renal function and prevent CRS4, by reduction the progression of renal and cardiac fibrosis.