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Determinants of thromboxane biosynthesis in patients with moderate to severe chronic kidney disease

      Highlights

      • Levels of both urinary 11-dehydro-TXB2 and 8-iso-PGF increased sequentially across the four CKD stages.
      • Both urinary prostanoids were inversely associated with eGFR and hemoglobin levels (P < 0.0001).
      • A significant direct correlation was observed between urinary 11-dehydro-TXB2 and 8-iso-PGF (P < 0.0001).
      • Urinary 8-iso-PGF, hemoglobin levels and eGFR were independent predictors of urinary 11-dehydro-TXB2.
      • This study provides biochemical evidence of persistent platelet activation in patients with CKD.

      Abstract

      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 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 increased sequentially across the four CKD stages (P < 0.0001, Kruskal–Wallis test). Both urinary prostanoids were inversely associated with either estimated glomerular filtration rate (eGFR, P < 0.0001) or hemoglobin levels (P < 0.0001). A significant direct correlation was also observed between urinary 11-dehydro-TXB2 and 8-iso-PGF (Rho = 0.620, P < 0.0001). On multivariate analysis, urinary 8-iso-PGF (β = 0.459, P < 0.0001), hemoglobin levels (β = − 0.261, P = 0.002) and eGFR (β = −0.172, P = 0.032) were independent predictors of urinary 11-dehydro-TXB2 (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.

      Abbreviations:

      CVD (cardiovascular disease), CKD (chronic renal disease), eGFR (estimated glomerular filtration rate), ROS (reactive oxidant species), PG (prostaglandin), Hb (hemoglobin), Scr (serum creatinine), MDRD (modification diet of renal disease study), EPO (erythropoietin), hs-CRP (high-sensitivity C reactive protein), TX (thromboxane), Clp (clopidogrel)

      Keywords

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