title: Determinants of thromboxane biosynthesis in patients with moderate to severe chronic kidney disease.
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.
  
  
  METHODS
  A cross sectional comparison between urinary 8-iso-PGF2α 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-PGF2α 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-PGF2α (Rho=0.620, P<0.0001). On multivariate analysis, urinary 8-iso-PGF2α (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 R(2)=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.
authors.affiliation: Internal Medicine and Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Chieti, Italy.
authors.forename: Natale
authors.initials: N
authors.lastname: Vazzana
authors.affiliation: Internal Medicine and Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Chieti, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Santilli
authors.affiliation: Internal Medicine and Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Chieti, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Lattanzio
authors.affiliation: Nephrology and Dialysis Unit, "S. Massimo" Hospital, Penne, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Liani
authors.affiliation: Italian Society of General Practitioners (SIMG), Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Giacci
authors.affiliation: Nephrology and Dialysis Unit, "G. Mazzini" Hospital, Teramo, Italy.
authors.forename: Goffredo
authors.initials: G
authors.lastname: Del Rosso
authors.affiliation: Internal Medicine Unit, Ortona-Guardiagrele Hospital, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Salvati
authors.affiliation: Internal Medicine and Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Chieti, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Boccatonda
authors.affiliation: San Raffaele Rome Open University, IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferroni
authors.affiliation: Internal Medicine and Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Chieti, Italy. Electronic address: gdavi@unich.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000652:urine; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D003430:Cross-Sectional Studies; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D004921:Erythropoietin / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007558:Italy; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018384:Oxidative Stress; D015539:Platelet Activation; D011453:Prostaglandins / Q000096:biosynthesis*; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000652:urine; D018570:Risk Assessment; D012307:Risk Factors; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D011453:Prostaglandins; D004921:Erythropoietin; C075750:8-epi-prostaglandin F2alpha; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D015237:Dinoprost
keywords: 11-dehydro-TXB(2); 8-iso-PGF(2α); CKD; Prostanoids; eGFR