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.
Subject(s)
Azathioprine/therapeutic use , Erythrocytes/enzymology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Methyltransferases/blood , Azathioprine/metabolism , Azathioprine/toxicity , Bone Marrow Diseases/chemically induced , Evaluation Studies as Topic , Genotype , Glutathione Transferase/genetics , Humans , Immunosuppressive Agents/metabolism , Immunosuppressive Agents/toxicity , Mercaptopurine/metabolism , Prospective StudiesABSTRACT
Azathioprine-induced myelosuppression is the most important side effect observed in kidney transplantation. We report a case of severe neutropenia after kidney transplantation due to a thiopurine methyltransferase deficiency. This cause of azathioprine-induced myelotoxicity is rare, but its infectious consequences may be severe. Thiopurine methyltransferase deficiency must therefore be suspected when early and severe leukopenia occurs during azathioprine therapy. Erythrocyte thiopurine methyltransferase activity measurement confirms the diagnosis. Azathioprine and 6-mercaptopurine must afterwards be definitively avoided.
