Theoretical and practical considerations in the use of hemodialysis for the therapeutic removal of asparagine and other amino acids

Abstract

The endogenous asparagine influx in mice undergoing asparaginase therapy can be neutralized by asparaginase activity equivalent to less than one lU/ml of plasma, as determined with a new, highly sensitive micro assay for asparaginase. It appears feasible that an asparagine influx of this magnitude may be cleared from the blood plasma by hemodialysis employing an artificial kidney apparatus with a clearance capacity somewhat greater than that routinely employed by renal patients. Application of this method for removing asparagine or other amino acids from the blood as an approach to cancer therapy ultimately depends upon the specific amino acid influx rates of the subject and upon the ability of the dialyzer to deplete the free amino acids in the blood plasma at a sufficiently high rate to lower specific amino acid concentrations in malignant tissues, or in adjoining interstitial spaces, to therapeutic levels. Based upon the data available, hemodialysis has potential therapeutic application as a means to control the removal of various free amino acids or other metabolic substrates from blood plasma.