Depletion by Hemodialysis of the Antioxidant Ergothioneine

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