Background: Clinical trials demonstrate either no benefit or increased risk of cardiovascular events and mortality in patients with chronic kidney disease (CKD) targeted for higher hemoglobin levels, who are treated with erythropoiesis-stimulating agents (ESAs). The mechanism underlying this observation remains unexplained.
Methods and results: We assessed platelet activation by measuring soluble P-selectin (sPsel), CD40 ligand (CD40L), and circulating microparticles (CMP) in patients with CKD. Higher hemoglobin levels were associated with increased Psel levels in patients on ESAs but not in ESA-naïve anemic and nonanemic patients. Psel positively correlated with CMP and CD40L in both anemic and nonanemic patients. Multivariate linear regression analysis revealed an association between increased Psel levels and hemoglobin concentration in patients receiving ESAs.
Conclusions: Anemic CKD patients on ESAs demonstrate increased levels of markers of platelet activation. These observations suggest a potentially complex interplay between platelet activation, impaired kidney function, and treatment of CKD anemia with ESAs.