Monitored high-dose azathioprine treatment reduces acute rejection episodes after renal transplantation.
Transplantation
; 66(3): 334-9, 1998 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-9721802
ABSTRACT
BACKGROUND:
Azathioprine (AZA) is widely used in organ transplantation. Common practice is to adjust dose according to body weight only, despite documented pharmacokinetic variability. The purpose of this study was to investigate whether high-dose AZA treatment monitored by 6-thioguanine nucleotides (6-TGN) levels reduces the incidence of rejection episodes in renal transplantation without a corresponding increase in myelotoxicity.METHODS:
Patients receiving cyclosporine, steroids, and AZA were randomized into either the low-dose AZA group (3 mg/kg on day 0, then 2 mg/kg/day the first week and 1 mg/kg/day thereafter) or the high-dose AZA group. In the latter, AZA was started at 5 mg/kg/day and then adjusted to keep 6-TGN concentrations (measured twice weekly) between 100 and 200 pmol/8 x 10(8) RBCs.RESULTS:
A total of 360 transplant recipients were included in the final analysis. The cumulative incidence of first rejection episodes was reduced by 21%, from 62.8% in the low-dose group to 49.4% in the high-dose group (difference 13.3%; 95% confidence interval 3.2-23.5). Similar results were found in subgroups according to HLA-DR match. The 6-TGN concentration was significantly higher in the high-dose AZA group during the first month, and the reduction in rejection episodes was achieved in the same period. A larger proportion of patients in the high-dose group had nadir white blood cell count below 2.0 x 10(9) leukocytes/L (13.3% vs. 4.4%; difference 8.9%; confidence interval 3.1-14.7).CONCLUSIONS:
High-dose AZA therapy in a triple-drug regimen, monitored by 6-TGN, will keep myelotoxicity within acceptable limits with the benefit of a reduction in acute rejection episodes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Azatioprina
/
Transplante de Rim
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Monitoramento de Medicamentos
/
Rejeição de Enxerto
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Imunossupressores
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
/
Adult
/
Aged
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Female
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Humans
/
Male
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Middle aged
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article