The amino acid content of plasma and erythrocytes in patients with severe renal failure (serum creatinine less than 8 mg/100 ml) treated with selective low-protein diets, in patients on regular hemodialysis, and in a control group of healthy subjects were studied. Most amino acids in erythrocytes of the patients showed the same changes as in plasma with the exception of histidine, serine, and alanine. In spite of low histidine plasma levels, the erythrocytes level is increased as compared with healthy controls. In uremic patients the plasma serine was constantly reduced whereas the serine content of the erythrocytes did not differ from healthy controls. Alanine concentrations in the erythrocytes of uremic patients were increased in spite of normal alanine plasma levels. This finding may be due to the increased glycolytic ratio of red cells from uremic subjects delivering more pyruvate for transmination to alanine. In the control group the cysteine content of erythrocytes was decreased with a gradient between plasma and erythrocytes of 3.5:1. The same gradient could be observed in uremic patients in spite of the elevation in their plasma cysteine levels by a factor of 2.7 compared with controls. The low cysteine levels in erythrocytes may be due to loss of cysteine for glutathione synthesis in red cells. High glutathione levels in the erythrocytes of uremic patients support this hypothesis.

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In 71 patients with different stages of renal disease, a close linear correlation was found between the concentration of "true creatinine" in the serum and that of 3methyl-histidine (r~0.79). First orientational investigations indicate that the excretion mechanism of 3-methyl-histidine is fundamentally different from that of histidine. Histidine is filtered glomerularly, and 5-7 % of the filtered volume appears in the urine; 3-methyl-histidine is filtered and secreted as well. In healthy subjects, the clearance of 3-methyl-histidine is three times higher than the endogenous creatinine clearance, and it falls below the creatinine clearance when renal function is severely impaired.