Human thiopurine S-methyltransferase activity in uremia and after renal transplantation

N. Weyer, T. Kröplin, L. Fricke, H. Iven*

*Corresponding author for this work
34 Citations (Scopus)


In addition to cyclosporin and steroids, azathioprine is frequently used for immunosuppression after renal transplantation. Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. A genetic polymorphism was shown with 1 in 300 homozygous for a TPMT deficiency. These subjects carry the risk of severe myelosuppression when treated with azathioprine. Objective: To investigate the influence of hemodialysis on TPMT activity in uremic patients and the effect of azathioprine treatment on enzyme activity. Methods: The assay for measurement of TPMT activity in packed red blood cells is based on a non-radioactive conversion of 6-thioguanine to 6-methylthioguanine. In 251 patients, TPMT activity was determined before and after a 4-h period of hemodialysis. In 49 patients (26 on azathioprine, 23 on mycophenolate mofetil as control group), TPMT activity was regularly determined during the first 120 days after renal transplantation. Results: TPMT activity is elevated in red blood cells of uremic patients before hemodialysis when compared with TPMT activity after hemodialysis. The latter is comparable to the activity in healthy subjects. In patients treated with azathioprine, the TPMT activity showed a slow increase that declined to pre-treatment values when azathioprine was withdrawn. This could not be observed in patients treated with mycophenolate mofetil. Conclusions: In uremic patients, TPMT activity is activated by some uremic factors that are removed by hemodialysis. In contrast to what has been observed before, dialysis shifted the TPMT activity close to that of a healthy control group. In patients treated with azathioprine after renal transplantation, the observed increase of TPMT activity could possibly be the result of enzyme induction.

Original languageEnglish
JournalEuropean Journal of Clinical Pharmacology
Issue number2
Pages (from-to)129-136
Number of pages8
Publication statusPublished - 28.05.2001

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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