Depletion by Hemodialysis of the Antioxidant Ergothioneine

Abstract

Background: Hemodialysis may excessively remove valuable solutes. Untargeted metabolomics data from a prior study suggested that ergothioneine was depleted in the plasma of hemodialysis subjects. Ergothioneine is a dietary-derived solute with antioxidant properties. The presence of a highly specific ergothioneine uptake transporter suggests that it is valuable. Ergothioneine levels are high in tissues susceptible to oxidative stress, particularly erythrocytes. We compared erythrocyte and plasma ergothioneine levels in subjects receiving hemodialysis to those in subjects with advanced chronic kidney disease (CKD) and subjects without known kidney disease (controls). We further examined the extent to which indiscriminate removal by hemodialysis could contribute to ergothioneine depletion. Methods: Liquid chromatography tandem mass spectrometry with stable isotope dilution was used to measure the erythrocyte and plasma levels of ergothioneine in 12 control, 12 CKD, and 11 hemodialysis subjects. We also measured the urinary excretion of ergothioneine in control and CKD subjects, and the dialytic removal of ergothioneine in hemodialysis subjects. Results: Erythrocyte ergothioneine levels were markedly reduced in CKD and hemodialysis subjects. Erythrocyte levels in CKD subjects were on average 24% of the levels in control subjects and were even lower in hemodialysis subjects, averaging 8% of control subjects. Plasma ergothioneine levels were also reduced in CKD and hemodialysis subjects but to a lesser extent than the erythrocyte levels. Kidney tubular reabsorption of ergothioneine was avid. In contrast, hemodialysis cleared ergothioneine at a rate of 146±36 ml/min so that removal of ergothioneine by hemodialysis greatly exceeded the amount excreted in the urine in both CKD and control subjects. Conclusions: Ergothioneine, a potentially valuable antioxidant, is severely depleted in people maintained on hemodialysis. Future studies are required to assess the consequences of ergothioneine depletion.