Mechanism of alteration of sodium potassium pump of erythrocytes from patients with chronic renal failure.

We examined intracellular electrolytes, K influx, and [3H]ouabain-binding capacity of erythrocytes from 32 normal subjects and 45 patients with end-stage renal failure on dialysis, including 16 with high intracellular Na (mean 17.3 +/- 3.9 mmol/liter cell water). The [3H]ouabain-binding capacity of erythrocytes with high cell Na was markedly reduced as compared with that of erythrocytes from normal subjects (274 +/- 52 vs. 455 +/- 59 sites/cell, P less than 0.001). The mean serum creatinine was higher in the uremic group with high cell Na. There was a significant linear correlation between intracellular Na and [3H]ouabain-binding in both normal and uremic subjects. Cross-incubation of normal cells with uremic plasma for 24 h failed to reduce [3H]ouabain-binding capacity of normal cells. In spite of a substantial increase in cell Na, K pump influx was not higher in uremic erythrocytes with high cell Na. When intracellular Na was altered with nystatin (cell Na equal to 120 mmol/liter cell water in both groups), K pump influx was proportional to the number of Na-K pump sites so that the ion turnover rate per pump site was similar in the two groups. Uremic plasma failed to depress K pump influx of normal erythrocytes. The passive net influx of Na in uremic cells with high intracellular Na was not different from that observed in erythrocytes from normal subjects. When erythrocytes were separated by age on Percoll density gradients, the number of Na-K pump sites of the youngest uremic cells was significantly lower than that of the youngest normal cells, suggesting that decreased synthesis of Na-K pump sites, rather than accelerated loss of Na-K pump sites during aging, was responsible for the decrease in [3H]ouabain-binding capacity of erythrocytes from uremic subjects. Taken together, these findings suggest that a decrease in the number of Na-K pump sites plays a major role in the abnormality of Na-K pump of erythrocytes from patients with chronic renal failure.