The Uremic Retention Solute p-Cresyl Sulfate and Markers of Endothelial Damage

摘要: Background Cardiovascular disease is highly prevalent in patients with chronic kidney disease. In hemodialysis patients, the protein-bound uremic retention solute p -cresol independently associated cardiovascular The underlying mechanisms have not been elucidated. Study Design (1) Prospective observational study of humans and (2) vitro human umbilical vein endothelial cells. Setting Hemodialysis patients. Factor -Cresol its main derivative -cresyl sulfate. Outcomes Endothelial dysfunction. Measurements We studied: relation between blood markers dysfunction, including soluble P-selectin microparticles; direct effects sulfate on cell cultures. Results a cohort 100 maintenance free serum concentrations (median, 11.7 μmol/L; interquartile range, 15.2) were directly circulating microparticles ( P = 0.007), but (mean, 37.7 ± 14.4 [SD] pg/mL). Other independent determinants degree greater phosphorus 4.8 1.5 mg/dL; 0.008) calcium 9.3 0.8 0.03), whereas treatment active vitamin D vintage 25 months; 0.04) inversely associated. vitro, induced dose-dependent increase shedding sulfate–induced generation microparticles. Limitations relationship vivo was mechanistically explored. Conclusion -Cresyl induces absence overt damage number These findings suggest that alters function