Background. Despite great improvement in patient and graft survival, the long-term morbidity and mortality in renal transplant recipients (RTRs) are still significant, with a high incidence of cardiovascular disease-related deaths. Methods. We investigated thromboxane (TXA2) biosynthesis and endothelial and coagulative activation in 65 patients who received a renal transplant. Results. The rate of TXA2 biosynthesis (urinary 11-dehydro-TXB2 excretion largely reflects platelet TXA2 production in vivo) was significantly (P < 0.0001) higher in RTRs than in healthy subjects. Plasma von Willebrand factor (vWF) and thrombin-antithrombin (TAT) complexes were significantly higher (P < 0.001) in RTRs compared with controls. Urinary 11-dehydro-TXB2 directly correlated with plasma vWF and cholesterol. We next examined the relative influence of cyclosporine A (CsA) on TXA2 biosynthesis and endothelial activation, comparing a group of RTRs not receiving CsA with an age- and sex-matched group of patients treated with CsA. Urinary excretion of 11-dehydro-TXB2 and plasma levels of vWF were significantly increased in RTRs who received CsA compared with those who did not. After an overall follow-up of 120 months, RTRs who experienced cardiovascular events had a higher frequency of abnormal plasma levels of vWF than patients who remained event free. Conclusion. Renal transplantation is associated with in vivo platelet activation highly related to endothelial activation. This is particularly evident in CsA-treated patients. Administration of drugs that are able to reduce or eliminate thromboxane-dependent platelet activation in vivo may be beneficial to reduce the risk of cardiovascular events in RTRs.

Averna, M., Barbagallo, C., Ganci, A., Giammarresi, C., Cefalù, A., Sparacino, V., et al. (2001). Determinants of enhanced thromboxane biosynthesis in renal transplantation. KIDNEY INTERNATIONAL, 59(4), 1574-1579 [10.1046/j.1523-1755.2001.0590041574.x].

Determinants of enhanced thromboxane biosynthesis in renal transplantation

AVERNA, Maurizio;BARBAGALLO, Carlo Maria;CEFALU', Angelo Baldassare;
2001

Abstract

Background. Despite great improvement in patient and graft survival, the long-term morbidity and mortality in renal transplant recipients (RTRs) are still significant, with a high incidence of cardiovascular disease-related deaths. Methods. We investigated thromboxane (TXA2) biosynthesis and endothelial and coagulative activation in 65 patients who received a renal transplant. Results. The rate of TXA2 biosynthesis (urinary 11-dehydro-TXB2 excretion largely reflects platelet TXA2 production in vivo) was significantly (P < 0.0001) higher in RTRs than in healthy subjects. Plasma von Willebrand factor (vWF) and thrombin-antithrombin (TAT) complexes were significantly higher (P < 0.001) in RTRs compared with controls. Urinary 11-dehydro-TXB2 directly correlated with plasma vWF and cholesterol. We next examined the relative influence of cyclosporine A (CsA) on TXA2 biosynthesis and endothelial activation, comparing a group of RTRs not receiving CsA with an age- and sex-matched group of patients treated with CsA. Urinary excretion of 11-dehydro-TXB2 and plasma levels of vWF were significantly increased in RTRs who received CsA compared with those who did not. After an overall follow-up of 120 months, RTRs who experienced cardiovascular events had a higher frequency of abnormal plasma levels of vWF than patients who remained event free. Conclusion. Renal transplantation is associated with in vivo platelet activation highly related to endothelial activation. This is particularly evident in CsA-treated patients. Administration of drugs that are able to reduce or eliminate thromboxane-dependent platelet activation in vivo may be beneficial to reduce the risk of cardiovascular events in RTRs.
Settore MED/09 - Medicina Interna
Averna, M., Barbagallo, C., Ganci, A., Giammarresi, C., Cefalù, A., Sparacino, V., et al. (2001). Determinants of enhanced thromboxane biosynthesis in renal transplantation. KIDNEY INTERNATIONAL, 59(4), 1574-1579 [10.1046/j.1523-1755.2001.0590041574.x].
File in questo prodotto:
File Dimensione Formato  
Determinants of enhanced thromboxane biosynthesis.pdf

accesso aperto

Descrizione: Articolo
Dimensione 127.82 kB
Formato Adobe PDF
127.82 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/184012
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 16
social impact