Associations of Indoxyl Sulfate and p-cresyl Sulfate with Serum Uncarboxylated Matrix γ-carboxyglutamate Protein in Chronic Kidney Disease Patients

Abstract

Background: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are two important protein-bound uremic retention solutes. Increased serum levels of IS and PCS are associated with cardiovascular calcification. Matrix γ-carboxyglutamate protein (MGP) is a potent inhibitor of vascular calcification and inactivated uncarboxylated MGP (ucMGP) is related to vascular calcification. Nevertheless, whether serum levels of IS and PCS are associated with the serum ucMGP level in chronic kidney disease (CKD) patients with different stages is unknown. background: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are two important protein-bound uremic retention solutes. Increased serum levels of IS and PCS are associated with cardiovascular calcification. Matrix γ-carboxyglutamate protein (MGP) is a potent inhibitor of vascular calcification, and inactivated uncarboxylated MGP (ucMGP) is related to vascular calcification. Nevertheless, whether serum levels of IS and PCS are associated with the serum ucMGP level in chronic kidney disease (CKD) patients with different stages is unknown. Method: This cross-sectional study enrolled 90 patients in different stages of chronic kidney disease. Serum levels of IS and PCS were determined. The serum concentration of ucMGP was measured with an enzyme-linked immunosorbent assay. Independent associations between serum total IS and PCS with ucMGP were evaluated. Results: The mean serum level of ucMGP in participants of this study is 10.78±5.22 μg/mL. Serum levels of the two above-mentioned uremic toxins and ucMGP were elevated commensurately with deteriorating renal function. The serum level of ucMPG was associated with total IS (r = 0.456, p < 0.001) and total PCS (r =0.413, p < 0.001) levels. Multiple linear regression analysis showed that ucMGP was significantly related to levels of IS (β = 0.442, p <0.001), but not the level of PCS concentrations after adjusting for other confounding variables. Conclusion: Our study showed that a higher serum IS level was independently associated with ucMGP in deteriorating CKD. Therefore, it would be worthwhile to investigate the effect of IS on ucMGP in the pathogenesis of vascular calcification in future studies.