Determinants of thromboxane biosynthesis in patients with moderate to severe 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, low grade inflammation and CKD-related anemia. Patients and methods: A cross sectional comparison between urinary 8-iso-PGF_2α and 11-dehydro-TXB₂, in vivo markers of oxidative stress and platelet activation, respectively, was performed in 115 patients with stage 1-4 CKD. Results: Levels of both urinary 11-dehydro-TXB₂ and 8-iso-PGF_2α increased sequentially across the four CKD stages (P2 and 8-iso-PGF_2α (Rho=0.620, P2α (β=0.459, P2 (adjusted R² =0.488). Conclusions: 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 TX-dependent platelet activation. This finding may provide a mechanistic link between CKD-related anemia and increased cardiovascular risk.