Diamine oxidase (histaminase) in chronic renal disease and its inhibition in vitro by methylguanidine.

The activity of plasma diamine oxidase (pyridoxal containing amine oxidase, histaminase, DAO), E. C. N. 1. 4. 3. 6., was found to be normal in 14 patients with chronic renal disease of different origins. However, after administration of heparin (200 IU/kg body weight, i.v.), the release of the enzyme into the plasma of the patients was markedly decreased when compared to that found in a group of 8 healthy volunteers. In patients with chronic renal failure the plasma concentration of pyridoxalphosphate, the coenzyme of DAO, was found to be significantly decreased. Furthermore methylguanidine, which is thought to be an important uremic toxin, was shown to be a potent non-competitive inhibitor of DAO in vitro (Ki5 X 10(5) M). The organ concentrations of methylguanidine are thought to correspond with the Ki value detected, as distribution studies using the tritiated toxin revealed organ accumulation up to five times the plasma level. Therefore, the decrease of DAO release after heparin stimulation in patients with chronic renal failure may be explained, in part, by inhibition of the enzyme as well as by a decreased coenzyme level. The results suggest that disturbed histamine metabolism may be involved in the production of some of the clinical symptoms commonly associated with chronic renal failure.