A VOLUME-INDEPENDENT COMPONENT TO POSTDIURETIC SODIUM RETENTION IN HUMANS

Net sodium (Na) loss during diuretic administration is limited by post diuretic renal salt retention. This could be a homeostatic response to extracellular fluid volume (ECV) depletion. However, rats infused wit h loop diuretics develop structural and functional adaptations in the distal nephron that enhance NaCl reabsorption. Therefore, the hypothes is that postdiuretic Na retention in humans contains a volume-independ ent component was tested. Normal volunteers were equilibrated to a 120 mmol/24 h Na intake. For the first protocol, subjects received, in ra ndom order, a placebo, bumetanide (B), or bumetanide accompanied by an infusion of an electrolyte solution at a rate adjusted to match urine flow and thereby to obviate Na losses (bumetanide plus volume replace ment; B + VR). After the completion of B diuresis, there was a positiv e Na balance that restored 70% of the Na loss within 42 h. However, th is positive Na balance was prevented by volume replacement (B + VR). F or the second protocol, subjects received, in random order, a placebo injection and a 100-mmol NaCl load (P + NaCl) or a bumetanide injectio n plus volume replacement in addition to a 1 00-mmol NaCl load (B + VR + NaCl). Over the ensuing 42 h, 94% of the load was eliminated when i t was infused alone (P + NaCl). In contrast, only 9% was eliminated wh en it was given with bumetanide and volume replacement (B + VR + NaCl) . It was concluded that postdiuretic Na retention in normal human subj ects is due both to ECV depletion and to volume-independent Na retenti on manifest as an inability to excrete a modest NaCl load. These findi ngs emphasize the importance of salt restriction both during loop diur etic therapy and after its withdrawal to obviate these powerful Na-ret aining mechanisms.