title: Monitoring of azathioprine-induced immunosuppression with thiopurine methyltransferase activity in kidney transplant recipients.
abstract: Thiopurine methyltransferase (TPMT), one of the enzymes involved in azathioprine metabolism, exhibits a wide range of activity in the normal population. We prospectively evaluated the monitoring of erythrocyte TPMT activity (using a radiochemical method) in kidney transplant recipients with regard to the efficacy of azathioprine. Three patterns in TPMT activity variation were observed. In group 1 patients, TPMT activity rose as early as 8 days after transplantation and steadily until month 3. In group 3 patients, TPMT activity remained unchanged. In group 2 patients, TPMT activity rose at month 1 after transplantation. Interestingly, the incidence of acute rejection was significantly (P < 0.01) different among the 3 groups, with the lowest incidence in group 1 and the highest in group 3. We hypothesized that TPMT activity increase was induced by azathioprine in the patients with the lowest incidence of acute rejection. The inducibility of TPMT activity would then appear to be an interesting marker of azathioprine-induced immunosuppression.
authors.affiliation: INSERM 75, CHU Necker, Université René Descartes, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Mircheva
authors.forename: C
authors.initials: C
authors.lastname: Legendre
authors.forename: C
authors.initials: C
authors.lastname: Soria-Royer
authors.forename: E
authors.initials: E
authors.lastname: Thervet
authors.forename: P
authors.initials: P
authors.lastname: Beaune
authors.forename: H
authors.initials: H
authors.lastname: Kreis
mesh_terms: D001379:Azathioprine / Q000378:metabolism / Q000627:therapeutic use* / Q000633:toxicity; D001855:Bone Marrow Diseases / Q000139:chemically induced; D004912:Erythrocytes / Q000201:enzymology*; D005069:Evaluation Studies as Topic; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000627:therapeutic use* / Q000633:toxicity; D016030:Kidney Transplantation / Q000276:immunology*; D015122:Mercaptopurine / Q000378:metabolism; D008780:Methyltransferases / Q000097:blood*; D011446:Prospective Studies
chemical_list: D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D005982:Glutathione Transferase; D001379:Azathioprine