Glutathione (GSH), the most abundant intracellular low molecular mass thiol, protects cells from oxidative damage and regulates their function. Available information is inconsistent regarding levels of GSH and its disulfide (GSSG) in maintenance hemodialysis patients (HD). In addition, very limited data are available in HD about the relationship of GSH and GSSG with other measures of thiol metabolism and with the clinical profile. We tested the hypothesis that erythrocyte GSH/GSSG redox potential (Eh) is lower in HD than in healthy controls (C), and that Eh correlates with posttranslational thiolation of hemoglobin (Hb) and with standard clinical parameters in HD. In cross-sectional comparison of 33 stable HD and 21 C, we found a net loss of reducing capacity in HD as indicated by low erythrocyte GSH/GSSG Eh (−257 ± 5.5 vs. −270 ± 5.6 mV, p=0.002). Glutathionylated Hb (HbSSG) was 46% higher in HD than C (19.3 ± 4.80 vs. 13.2 ± 2.79 pmol/mg Hb; p = 0.001) and cysteinylated Hb (HbSSCy) was >3-fold higher in HD than C [38.3 (29.0 – 63.3) vs. 11.5 (9.6 – 17.2) pmol/mg Hb; p = 0.001]. In multiple regression analysis of the HD cases, statistically significant associations were found between the GSH/GSSG Eh and the BUN (p = 0.001), creatinine (p = 0.015) and nPCR (p = 0.05), after adjusting for age, race/ethnicity and etiology of end-stage renal disease (ESRD). In conclusion, accurate and precise analysis of GSH, GSSG and mixed disulfides reveals loss of erythrocyte GSH/GSSG Eh, rise of both HbSSG and HbSSCy, and correlation of these thiols with measures of uremia and dietary protein intake.

In a relatively small cohort of clinically stable MHD patients, the veterans showed equivalent nutrition status and dietary intake and less inflammation than the nonveterans, thus not supporting the possibility that veteran MHD patients may have worse nutrition than the nonveteran counterpart.