Abstract 375

Azathioprine is a prodrug commonly used in immunosuppressive regimen after renal transplantation. After conversion to 6-mercaptopurine, the drug is metabolized into the active 6-thiopurine nucleotides and is catabolized to methyl 6-mercaptopurine by the thiopurine methyltransferase (TPMT), an enzyme under genetic control. In the present study, the inter and intraindividual variations of red blood cell TPMT and the relationship with the effects of azathioprine were evaluated during the first year post-renal transplantation in 22 paediatric patients. The initial TPMT activity and 6-TGN were not related to the occurrence of rejection episodes during the period of the study. In contrast, both TPMT activity and percentage of variation from baseline determined at month 1 were higher in the 11/22 patients who rejected by comparison with those that did not reject during the first year following transplantation (p<0.005 ; figure 1). Moreover, 16/18 (88%) rejection episodes occurred during the first year in 9 patients having TPMT activity over 25.0 nmol/h/ml (range 25.3 to 34.2) at month 1 and a significant relationship (p<0.01) was found between the number of rejection episodes during the first year and both TPMT activity and variation from baseline determined at month 1 (p<0.001). Three patients were genotyped TPMT heterozygous (TPMT*1/*3A n=2 and TPMT*1/*2 n=1) with initial TPMT activity below 14.0 nmol/h/ml and two of them experienced increase of TPMT activity during the first month. Our preliminary results suggest a link between occurrence of rejection and high red blood cell TPMT activity, probably associated with high catabolism of azathioprine.

Figure 1
figure 1

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