Renal sodium handling in acute and chronic salt loading/depletion protocols: the confounding influence of acute water loading

Objectives Renal tubular sodium handling was measured in healthy subjects s ubmitted to acute and chronic salt-repletion/salt-depletion protocols. The goal was to compare the changes in proximal and distal sodium handling indu ced by the two procedures using the lithium clearance technique. Methods In nine subjects, acute salt loading was obtained with a 2 h infusi on of isotonic saline, and salt depletion was induced with a low-salt diet and furosemide. In the chronic protocol, 15 subjects randomly received a lo w-, a regular- and a high-sodium diet for 1 week In both protocols, renal a nd systemic haemodynamics and urinary electrolyte excretion were measured a fter an acute water load. In the chronic study, sodium handling was also de termined, based on 12 h day- and night-time urine collections. Results The acute and chronic protocols induced comparable changes in sodiu m excretion, renal haemodynamics and hormonal responses. Yet, the relative contribution of the proximal and distal nephrons to sodium excretion in res ponse to salt loading and depletion differed in the two protocols. Acutely, subjects appeared to regulate sodium balance mainly by the distal nephron, with little contribution of the proximal tubule, In contrast, in the chron ic protocol, changes in sodium reabsorption could be measured both in the p roximal and distal nephrons. Acute water loading was an important confoundi ng factor which increased sodium excretion by reducing proximal sodium reab sorption. This interference of water was particularly marked in salt-deplet ed subjects. Conclusion Acute and chronic salt loading/salt depletion protocols investig ate different renal mechanisms of control of sodium balance. The endogenous lithium clearance technique is a reliable method to assess proximal sodium reabsorption in humans. However, to investigate sodium handling in disease s such as hypertension, lithium should be measured preferably on 24 h or ov ernight urine collections to avoid the confounding influence of water. J Hy pertens 18:1657-1664 (C) 2000 Lippincott Williams & Wilkins.