Abstract 194: Determinants of Platelet Activation in Chronic Kidney Disease
Background. Mechanisms of accelerated atherothrombosis in patients with chronic kidney disease (CKD) are only partly characterized. The aims of this study were to evaluate the extent of thromboxane (TX)-dependent platelet activation in patients with CKD, and to characterize the determinants of altered TX biosynthesis in this setting, with particular reference to enhanced lipid peroxidation and the hyperactivity of the ligand-RAGE axis.
Methods. A cross sectional comparison between urinary 8-iso-PGF2α and 11-dehydro-TXB2, in vivo markers of oxidative stress and platelet activation, respectively, and plasma endogenous secretory (es)RAGE has been performed in 95 patients with CKD and 20 healthy controls.
Results. Urinary 8-iso-PGF2α and 11-dehydro-TXB2 were significantly higher in CKD patients as compared to healthy controls (P<0.0001). A significant direct correlation has been found between urinary 8-iso-PGF2α and 11-dehydro-TXB2 (Rho = 0.47, P < 0.0001). In CKD patients, urinary 11-dehydro-TXB2 was inversely related with estimated glomerular filtration rate (eGFR) (Rho=-0.35, P=0.001) and hemoglobin levels (Rho = -0.53, P < 0.0001). In addition, plasma esRAGE levels were inversely related with eGFR (Rho=-0.30, P=0.006). On multivariate analysis, urinary 8-iso-PGF2α and hemoglobin levels were the only independent predictors of urinary 11-dehydro-TXB2 levels.
Discussion. This study provides biochemical evidence of persistent platelet activation in patients with CKD. This condition occurs early in the natural history of the disease and is related to kidney function and oxidative stress. Moreover, we found an independent inverse relationship between hemoglobin levels and thromboxane-dependent platelet activation. This finding may provide mechanicistic link between CKD-related anemia and increased cardiovascular risk.
- © 2012 by American Heart Association, Inc.