THE METABOLISM OF AZATHIOPRINE IN RENAL FAILURE

Abstract

SUMMARY The influence of renal failure on azathioprine activity has been studied with regard to its toxicity and immunosuppression. Hematological toxicity was studied by the analysis of clinical data on 59 patients treated continually with azathioprine for long periods. Renal failure did not favor the incidence, precocity, or duration of leukopenia. Immunosuppressive activity was studied by the rosette inhibition test; it was not different in 15 patients with renal failure and in 16 normal subjects, even in cases of bilateral nephrectomy. Conversely, when azathioprine was labeled with 35S it was observed that the metabolism of 35S was very abnormal, with an important delay in the disappearance of the activity. Finally, renal failure decreases the rate of elimination of azathioprine metabolites but does not modify its biological activities, probably because of a very rapid metabolic inactivation of the biologically active metabolites. Practically, azathioprine dosage does not have to be reduced in cases of renal failure. The methods used study the influence of renal failure on immunosuppressive activity and toxicity of azathioprine, but they are not specific for azathioprine and could be used for other immunosuppressive agents.