SUSTAINED VOLUME EXPANSION AND [NA,K]ATPASE INHIBITION IN CHRONIC-RENAL-FAILURE

Hypotheses regarding the pathogenesis of volume-dependent hypertension have invoked an endogenous sodium pump inhibitor or digitalis-like fa ctor (DLF) to link altered sodium homeostasis to the rise in blood pre ssure. Our goal was to develop a clinical protocol that achieved predi ctable, sustained volume expansion, with the premise that renal failur e patients on peritoneal dialysis would increase intravascular volume, gain weight, and raise blood pressure (BP) in relation to measured in creases in DLF. In a 5-day protocol, dialysis was kept constant but di etary NaCl and fluids were modified in 7 patients. DLF was measured as inhibition of [Na,K]ATPase. Likewise, the first 2 L of daily peritone al dialysate (PD) was processed on HPLC and the eluate analyzed for DL F. The group achieved significant weight gain (WT) by day 3 (Delta WT = 4.1 +/- 1.2 kg, P < .05). Likewise, mean arterial pressure (MAP) and plasma DLF activity increased significantly. All variables were highl y correlated (DLF v WT: R = 0.88, P = .004; MAP v DLF: R = 0.82, P = . 01; MAP v WT: R = 0.90, P = .003). Although a number of HPLC fractions contained agents that interacted with the assay, only one PD HPLC fra ction (at 19.5 min) contained DLF activity that correlated with change s in MAP (R = 0.60, P = .002), and body weight (R = 0.67, P = .0003). We conclude that candidate DLF responds to sustained volume expansion and the relationship suggests that it could influence blood pressure. Moreover, the application of stringent criteria to the confusing array of factors in plasma that may affect assays for DLF appears to reduce the field dramatically, to a single candidate in this setting.