Correction of uremic cellular injury with a protein-restricted amino acid-supplemented diet

Untreated patients with uremia show an abnormally low resting transmembrane potential (Em) of skeletal muscle cells. This finding corresponds to impaired sodium transport. Adequate hemodialysis corrects this abnormality. Toxins derived from protein precursors have been implicated as the hypothetical cause of impaired transport and membrane depolarization in untreated uremia. To inferentially examine this hypothesis in further detail, we deliberately reduced dialysis time until Em fell in six uremic patients in whom it had been previously corrected. When Em fell, we examined the effect of reducing crude protein in their diet in conjunction with adding an essential amino acid supplement. Five of six patients who complied with the diet showed correction of their abnormally low Em despite continued reduction of dialysis time. These findings support the notion that in patients with uremia, a product of crude dietary protein may be responsible for membrane depolarization and, in addition, direct measurement of resting muscle transmembrane potential may be a useful index to determine adequacy of dialysis therapy.