ABSTRACTTo evaluate their toxicity at the cellular level, middle molecules from uremic serum were incubated with erythrocytes from healthy subjects and the activity of the enzyme Delta‐aminolevulinic acid dehydrase (D‐ALA‐D) and peroxidative hemolysis were investigated. Uremic middle molecules caused a significant decrease of the D‐ALA‐D activity of normal erythrocytes which was not due to differences in the concentrations of Pb, Cd or Zn. The decreased enzyme activity could be restored by adding reduced glutathione (GSH; 5 mmol/L) together with the middle molecules to the assay system. Uremic middle molecules caused a significant increase of peroxidative hemolysis in normal erythrocytes.Uremic middle molecules contribute to the anemia of uremic patients by impeding hemoglobin synthesis and by increasing peroxidative hemolysis, possibly by affecting SH‐groups. H2O2‐producing compounds should be avoided in ur
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