Depletion of the Antioxidant Ergothioneine by Critical Illness and Continuous Renal Replacement Therapy.

Background: Ergothioneine is a diet-derived antioxidant with a specific membrane transporter that uptakes it into tissues susceptible to oxidative stress. We previously found that efficient dialytic clearance leads to marked ergothioneine depletion in patients on hemodialysis. Continuous renal replacement therapy (CRRT) provides higher time-averaged clearances of small solutes than hemodialysis. We therefore examined whether ergothioneine is depleted in patients receiving CRRT. Methods: We first compared erythrocyte and plasma ergothioneine levels in 19 critically ill subjects maintained on CRRT for ≥2 days (CRRT), 18 critically ill subjects without kidney impairment (CI), and 15 healthy subjects (control). We then examined the degree to which initiation of CRRT reduced ergothioneine levels in a separate group of 11 subjects after ≥2 days on CRRT and measured ergothioneine in the effluent fluid to calculate its CRRT clearance. Results: Compared to controls, erythrocyte and plasma ergothioneine levels were depleted in both critically ill subjects maintained on CRRT for 20 ± 26 days and critically ill subjects not on CRRT (erythrocyte: CRRT 226 ± 121 μM, CI 208 ± 132 μM, control 593 ± 568 μM; plasma: CRRT 0.52 ± 0.37 μM, CI 0.86 ± 0.83 μM, control 2.3 ± 1.7 μM). Initiation of CRRT in a separate group of 11 subjects significantly reduced the plasma level but not the erythrocyte level of ergothioneine after 3.4 ± 1.0 days. CRRT provided similar efficient clearances of ergothioneine, urea, and creatinine (31 ± 8, 38 ± 8, and 36 ± 10 mL/min). Conclusions: Ergothioneine is significantly depleted in critically illness, and prolonged CRRT may worsen the depletion. Our findings motivate further investigation of the impact of ergothioneine depletion in critical illness.