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Determinants of enhanced thromboxane biosynthesis in renal transplantation
- Source :
- Kidney International. (4):1574-1579
- Publisher :
- International Society of Nephrology. Published by Elsevier Inc.
-
Abstract
- Determinants of enhanced thromboxane biosynthesis in renal transplantation.BackgroundDespite 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.MethodsWe investigated thromboxane (TXA2) biosynthesis and endothelial and coagulative activation in 65 patients who received a renal transplant.ResultsThe 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.ConclusionRenal 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.
- Subjects :
- Male
Settore MED/09 - Medicina Interna
Thromboxane
graft survival
von Willebrand factor
Immunosuppressive Agent
Thromboxane A2
chemistry.chemical_compound
Reference Values
Renal Dialysi
cardiovascular disease
Reference Value
Platelet
Postoperative Period
Kidney transplantation
Kidney
immunosuppression
nephrotoxicity
Thromboxanes
Middle Aged
Cholesterol
medicine.anatomical_structure
Nephrology
Cyclosporine
Female
Cardiovascular disease
Graft survival
Immunosuppression
Nephrotoxicity
Von Willebrand factor
Adult
Antithrombin III
Cardiovascular Diseases
Follow-Up Studies
Humans
Immunosuppressive Agents
Peptide Hydrolases
Renal Dialysis
von Willebrand Factor
Kidney Transplantation
Human
circulatory and respiratory physiology
medicine.medical_specialty
Urology
kidney transplantation
Follow-Up Studie
Endothelial activation
medicine
Platelet activation
cardiovascular diseases
von willebrand factor
business.industry
medicine.disease
Transplantation
Peptide Hydrolase
chemistry
Immunology
business
Subjects
Details
- Language :
- English
- ISSN :
- 00852538
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Kidney International
- Accession number :
- edsair.doi.dedup.....ecedfe15640d1fa67c340f5b5976b106
- Full Text :
- https://doi.org/10.1046/j.1523-1755.2001.0590041574.x