Volume expansion in renal failure patients: a paradigm for a clinically relevant [Na,K]ATPase inhibitor

A volume-sensitive inhibitor of [Na,K]ATPase, termed the digitalis-like factor (DLF), is postulated to participate in hypertension. To test this hypothesis, end-stage renal failure patients on peritoneal dialysis were placed on a clinical protocol that brought about a gradual, sustained volume expansion. This was accompanied by significant increases in body weight (4.1 +/- 1.2 kg, p < 0.05), mean arterial pressure (18.2 +/- 6.4 mm Hg, p < 0.05), and serum DLF activity (4.7 +/- 1.9% inhibition, p < 0.05). Processing these patients' daily dialysates by ultrafiltration and high-performance liquid chromatography allowed for the identification of a single elution fraction having volume-sensitive [Na,K]ATPase inhibitory activity. This factor in turn was correlated with serum DLF activity (R = 0.60, p = 0.002), weight gain (R = 0.67, p = 0.0003), and mean arterial pressure (R = 0.59, p = 0.003). This factor was readily distinguished from ouabain and digoxin but was similar to the DLF isolated from amniotic fluid. These results suggest that volume expansion in renal failure patients on peritoneal dialysis gives rise to a unique volume-sensitive DLF that may contribute to these patients' increase in blood pressure.