Studies on the characteristics of the control system governing sodium excretion in uremic man

Abstract

A B S T R A C T Sodium excretion was studied in a group of patients with chronic renal disease, (a) on constant salt intakes of varying amounts with and without mineralocorticoid hormone adminwitration and, (b) after acute extracellular fluid volume expansion. The lower the steady-state glomerular filtration rate (GFR), the greater was the fraction of filtered sodium excreted on both a 3.5 and 7.0 g salt diet; and the lower the GFR, the greater was the change in fractional excretion in the transition from the 3.5 to the 7.0 g salt diet. This regulatory capacity did not appear to be influenced by mineralocorticoid hormone administration. After acute expansion of extracellular fluid (ECF) volume, the increment in sodium excretion exceeded the concomitant increment in filtered sodium in six of nine studies and in the remaining three studies, the increment in excretion averaged 59% of the A filtered load (i.e., only 41%b of the increase in filtered sodium was reabsorbed). During saline loading, the decrease in fractional reabsorption of sodium tended to vary inversely with the steady-state GFR, although all patients received approximately the same loading volume.When an edema-forming stimulus was applied during saline infusion, the natriuretic response was aborted and the lag time was relatively short. When GFR and the filtered load of sodium were increased without volume expansion, the A sodium excretion averaged only 19% of the A filtered load; moreover, changes in fractional sodium reabsorption were considerably smaller than those observed during saline loading. The data implicate the presence of a factor other than GFR and mineralocorticoid changes in the modulation of sodium excretion in uremic man. INTRODUCTIONIt is unusual for a patient with chronically progressive renal disease either to accumulate edema or to sustain net sodium loss on an average salt intake. If this clinical observation reflects a continuing ability to maintain external sodium balance in the face of a diminishing number of functioning nephrons, sodium excretion/nephron must increase with time. Moreover, if external sodium balance is maintained on an unrestricted salt intake, the range over which sodium excretion varies in single nephrons must increase progressively as the nephron population decreases if ordinary dayto-day variations in salt intake are to be accommodated. Thus, to effect a change in total sodium excretion of any given magnitude, the average change in excretion per nephron must vary inversely with the number of nephrons. If this requirement for exaggerated changes in sodium excretion (per nephron) is fulfilled in chronic renal disease, an unusual opportunity might exist to distinguish tubular from glomerular contributions to the regulation of sodium excretion.In the present study some aspects of the control of sodium excretion have been studied in uremic patients.

Micropuncture Studies of Sodium Tranport in the Remnant Kidney of the Dog THE EFFECT OF GRADED VOLUME EXPANSION

“…Although altered renal transport of sodium in chronic renal failure is well known and has been the subject of intensive investgation (1)(2)(3)(4)(5)(6)(7)(8)(9)(17)(18)(19), the manner by wnvhich this change in renal handling of sodium takes place at various sites of the nephron has not been elucidated. Micropuncture studies performed in the past using various experimental models have centered mostly on the transport changes in the proximal tubule (5)(6)(7)(8) and rarely in the distal segments (9).…”

On the influence of extracellular fluid volume expansion and of uremia on bicarbonate reabsorption in man

“…Both volume expansion and nephron reduction may be attended by an increase in GFR per nephron especially in the superficial nephrons (12,13). The effects of either acute or chronic hyperfiltration on the kinetics of bicarbonate reabsorption remain to be established and although the experimental induction of hyperfiltration both in normal dogs (14) and uremic man (11) does not influence fractional sodium excretion, the possibility was considered that the decrease in bicarbonate reabsorption expressed per unit of GFR seen with exaggerated ECF volume expansion was secondary to an increase in GFR per nephron rather than to inhibition of bicarbonate reabsorption. However, the opportunity to compare absolute rates of bicarbonate reabsorption at comparable levels of GFR Effects of ECF Volume Expansion and Uremia on Bicarbonate Reabsorption and comparable plasma bicarbonate concentrations existed in three of the subjects studied during both minimized and exaggerated expansion.…”

The Influence of Extracellular Fluid Volume on the Renal Bicarbonate Threshold. A Study of Two Children with Lowe's Syndrome

“…Characteristically, its action is independent of changes of GFR or mineralocorticoid activity. Most recently, the action of the third factor in modulating sodium reabsorption has been demonstrated in uremic man [19]. The fraction of filtered sodium reabsorbed in renal insufficiency is less than that in the normal condition.…”