1. We have reported a normal sodium (Na) pump, but decreased loop-diuretic-sensitive Na efflux in erythrocytes from patients with chronic renal failure on haemodialysis, suggesting a different mode of co-transport in uraemia.
2. The present work extends these findings and examines in vitro simultaneous unidirectional and radiolabelled Na and K fluxes through the Na/K/Cl co-transport and the Na/K pump in washed erythrocytes from seven subjects with chronic renal failure and seven controls. Erythrocyte cytosolic calcium was also examined.
3. Ouabain-sensitive 86Rb influx was similar in patients and controls (1.76 ± 0.19 versus 1.72 ± 0.13 mmol h−1 litre−1 of erythrocytes) as was ouabain-sensitive 22Na efflux (3.62 ± 0.36 versus 4.04 ± 0.39 mmol h−1 litre−1 of erythrocytes).
4. Bumetanide-sensitive 86Rb and 22Na influx and 22Na efflux were measured at three concentrations (4, 8 and 12 mmol/l) of external K. In chronic renal failure, mean bumetanide-sensitive 22Na efflux was decreased at all external K concentrations compared with controls, and at physiological concentrations (4 mmol/l) external K was lower than controls (0.14 ± 0.01 versus 0.38 ± 0.05 mmol h−1 litre−1 of erythrocytes, P < 0.01). Mean bumetanide-sensitive 86Rb influx was also reduced in chronic renal failure at all external K concentrations, and at 4 mmol/l external K was lower than controls (0.13 ± 0.04 versus 0.34 ± 0.04 mmol h−1 litre−1 of erythrocytes, P < 0.01). Conversely, bumetanide-sensitive 22Na influx was markedly increased at all external K levels in chronic renal failure, and at 4 mmol/l external K values were elevated compared with controls (0.64 ± 0.18 versus 0.34 ± 0.04 mmol h−1 litre−1 of erythrocytes, P < 0.001). The mean cytosolic calcium concentration was higher in erythrocytes in chronic renal failure than controls (134.4 ± 8.6 versus 63.7 ± 5.8 nmol/l, P < 0.001).
5. Thus, in washed erythrocytes incubated in artificial media there is a markedly increased ouabain-insensitive Na influx in subjects with chronic renal failure which might be explained in part by the higher levels of cytosolic calcium. In vivo, this cell defect combined with suppression of the Na/K pump could lead to intracellular Na accumulation and play a role in uraemic complications.