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CHRONIC THROMBOXANE SYNTHASE INHIBITION WITH CGS 12970 IN HUMAN CYCLOSPORINE NEPHROTOXICITY1
- Source :
- Transplantation. 56:1422-1426
- Publication Year :
- 1993
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 1993.
-
Abstract
- CsA nephrotoxicity in rats is associated with an increase in renal thromboxane production. Treatment with selective thromboxane synthase inhibitors or receptor antagonists improves renal function in these animal models. In humans, it is unclear whether intervention aimed at reducing the effects of thromboxane on the kidney will be clinically useful. However, we reported previously that thromboxane metabolite excretion is increased in CsA-treated renal allograft recipients with evidence of CsA toxicity and that 48-hr intravenous infusion of the selective thromboxane synthase inhibitor CGS 13080 improves renal function in such patients. We undertook the present study to determine the effect of more prolonged treatment with an oral thromboxane synthase inhibitor, CGS 12970, in renal transplant recipients taking CsA. We measured glomerular filtration rate and p-aminohippurate clearance before and after 4 weeks of treatment with CGS 12970 in 13 patients with renal allografts who had been treated with CsA for a mean 6.3 months and had mild renal insufficiency. Baseline serum creatinine was 1.8 +/- 0.3. Treatment with CGS 12970 resulted in 83% inhibition of urinary thromboxane B2 (TXB2), 93% inhibition of 2,3-dinor-TXB2, and 89% inhibition of 11-dehydro-TXB2, but no change in the urinary excretion of prostacyclin metabolites. However, suppression of urinary thromboxane metabolites to these levels did not significantly affect renal function. Glomerular filtration rate was 45 +/- 4 ml/min/1.73 m2 at baseline and 43 +/- 4 ml/min/1.73 m2 after 4 weeks of treatment with CGS 12970. Estimated renal plasma flow was 272 +/- 21 ml/min/1.73 m2 at baseline and 251 +/- 38 ml/min/1.73 m2 with thromboxane synthase inhibition. Thus, substantial suppression of thromboxane production with CGS 12970 did not improve renal function in CsA-treated renal allograft recipients.
- Subjects :
- Transplantation
Kidney
medicine.medical_specialty
Creatinine
biology
Thromboxane
urologic and male genital diseases
Nephrotoxicity
Thromboxane B2
Thromboxane Production
chemistry.chemical_compound
medicine.anatomical_structure
Endocrinology
chemistry
Renal blood flow
Internal medicine
medicine
biology.protein
Thromboxane-A synthase
Subjects
Details
- ISSN :
- 00411337
- Volume :
- 56
- Database :
- OpenAIRE
- Journal :
- Transplantation
- Accession number :
- edsair.doi...........71c8a8db5e0e56fd2d531c86e050da7b