EFFECT OF UREA DIURESIS ON RENAL EXCRETION OF ELECTROLYTES

Abstract

Extreme degrees of osmotic diuresis were produced in anesthetized dogs by the intravenous infusion of a soln. of 50% urea sufficiently rapidly to produce plasma concns. of urea in excess of 100 mosM/l. within a period of a few hrs. Water balance was maintained by infusing solns. of NaCl at a rate commensurate with urine flow. By this technique glomerular filtration rate was maintained at or near control levels until depressed by inordinately high concns. of urea. The animals,showed the following responses: Urine flow progressively increased and in many expts. reached 50% of the glomerular filtration rate. At high rates of flow the urine became approx. isosmotic with the blood, which indicated the functional incapacity of the distal tubule to alter significantly the composition of the large volume of filtrate it received. Thus differences between the composition of the glomerular filtrate and the formed urine were interpreted as largely the result of activity of the proximal tubule. The tubular reabsorbate was isosmotic and, since only small amts. of urea were reabsorbed, Na salts provided the major osmotic constituent of the reabsorbate. This resulted in a Na concn. of the reabsorbate greatly in excess of that of the filtrate or plasma. A concn. gradient relative to Na between proximal tubular filtrate and reabsorbate indicates an active transfer of Na by proximal tubular cells. The isotonicity of the formed urine is readily explained by the back diffusion of water due to the osmotic gradient created by the transfer of Na. The presence of urea in the proximal tubule greatly diminished the reabsorption of Na even though the Na load remains constant. Arguments are presented which favor the view that total Na reabsorption is decreased because of the continuous fall in proximal tubular Na concn. as each increment of the glomerular filtrate is reabsorbed, a condition which only applies in the presence of an osmotic diuretic. The admn. of a mercurial diuretic at the height of urea diuresis further decreases the tubular reabsorption of Na but does not alter the concn. gradient relative to Na between tubular urine and reabsorbate. This indicates that mercurial diuretics decrease the functional capacity of the proximal tubular cells actively to transfer Na but do not alter the fundamental mechanisms of Na reabsorption. The data obtained on the renal clearance of urea at high plasma levels are in keeping with the view that the excretion of urea is a process of filtration and passive back diffusion. The problem of renal work is discussed in relation to the exptl. results.