RESTING SKELETAL-MUSCLE MEMBRANE-POTENTIAL AS AN INDEX OF UREMIC TOXICITY - PROPOSED NEW METHOD TO ASSESS ADEQUACY OF HEMODIALYSIS

Electrochemical disturbances of skeletal muscle cells in untreated uremia are characterized by an increase in the intracellular Na and Cl content, a decrease in intracellular K and a low resting membrane potential. The foregoing was reexamined and the effects of hemodialysis were examined. Three groups of patients were studied. In the 1st group of 22 uncomplicated uremic patients, whose creatinine clearance (Ccr) ranged from 2-12 cm3/min per 1.73 m2, resting transmembrane potential difference (Em) of skeletal muscle cells was measured. In each of the 9 patients whose Ccr ranged between 6.3 and 12 cm3/min, the Em was normal (i.e., -90.8 .+-. 0.9 mV, mean .+-. SEM). As Ccr dropped below 6.3 cm/min, the Em became progressively reduced and assumed a linear relationship with the Ccr. In the 2nd study, 9 individuals with endstage renal disease, whose mean Ccr was 4.3 cm3/min, underwent measurement of Em and intracellular electrolyte concentration before and after 7 wk of hemodialysis. Before dialysis, the Em was -78.5 .+-. 2.1 mV, intracellular Na and Cl were elevated and the intracellular K was reduced. After 7 wk of hemodialysis the Em rose to -87.8 .+-. 1.3 mV, and the intracellular Na, Cl and K became normal. In the 3rd study, 7 patients who were stable on 6-h thrice-weekly dialysis were studied before and after reduction of dialysis to 6 h twice weekly. In those individuals whose Em remained normal after 6 wk, dialysis time was reduced further. On trice-weekly dialysis the Em was -91.2 .+-. 1.0 mV. With reduced dialysis, the Em fell to -80.1 .+-. 0.8 mV (P < 0.001). In each case, the Em became abnormal before significant signs or symptoms of uremia were noted. End-stage renal disease is associated with serious electrochemical changes in the muscle cell which are reversed by hemodialysis and recur when dialysis time is reduced. Serial observations of muscle Em may be a potentially powerful tool to assess adequacy of dialysis therapy.