Determinants of enhanced thromboxane biosynthesis in renal transplantation.
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.


CONCLUSIONS
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.
Department of Medicine and Aging, University G. D'Annunzio, Chieti, Italy.
M
M
Averna
C M
CM
Barbagallo
A
A
Ganci
C
C
Giammarresi
A B
AB
Cefalù
V
V
Sparacino
F
F
Caputo
S
S
Basili
A
A
Notarbartolo
G
G
Davì
D000328:Adult; D000990:Antithrombin III; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality; D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood; D011184:Postoperative Period; D012016:Reference Values; D006435:Renal Dialysis; D013931:Thromboxanes / Q000096:biosynthesis*; D014841:von Willebrand Factor / Q000032:analysis
D007166:Immunosuppressive Agents; D013931:Thromboxanes; C046193:antithrombin III-protease complex; D014841:von Willebrand Factor; D016572:Cyclosporine; D000990:Antithrombin III; D002784:Cholesterol; D010447:Peptide Hydrolases