Renal T&&w Regdation of Urea Excretion irz Mm&”

MURDAUGH, HERSCHEL V., JR., BODIL SCHMIDT-NIELSEN, ELEANOR M. DonE Am R~BERX~ OTDELL. Renal tuhilar regulation oj wea escvetiou ilt man. J. Appl. Physiol. 13(z): 263-268. q&-Adult; male subjects were studied on a normal protein diet and on a low protein diet (basic rice diet with salt and fat supplements). Simultaneous inulin and urea clearances and total solute excretion were determined at high and low rates of urine flow on both diets. The glomerular filtration rate (GFR) was not altered by the low protein intake with salt added to the diet.. After 5 \ weeks of low protein intake there was a marked decrease in the fraction of filtered urea excreted at low urine flows. This difference was not apparent during maximal water diuresis (inulin U/P < IS). At lower rates of urine flow (inulin U/P > IS) the fraction of filtered urea excreted at any given rate of urine flow was less than that found during normal protein intake. This difference increased at progressively lower rates of urine flow. The decrease in the fraction of filtered urea excreted during low protein intake was apparently not caused by changes in the rate of urine flow, GFR, plasma urea concentration, or total solute excretion. These findings indicate renal tubular regulation of urea excretion in man of a nature similar to that found in other mammals. I T HAS BEEN demonstrated in kangaroo rats (I), white rats (2), camels (3) and in sheep (4, 5> that the urea clearance varies with the protein content of the diet. Furthermore, it has been found in camels and sheep that the change cannot be related to changes in glomerular filtration rate (GFR), plasma urea concentration, or osmotic load. These observations, therefore, show that the renal excretion of urea is regulated on the tubular level. According to the accepted concept for urea excretion in mammals, tubular regulation is not supposed to occur and it is assumed that urea is excreted by a mechanism of filtration and passive diffusion alone (6). The results mentioned above are thus in disagreement with the accepted concept. In spite of the commonly accepted view, the existing literature contains some evidence supporting the existence of renal tubular regulation of urea excretion also in man (7). However, the findings have not been conclusive and it seemed desirable to study the effects of altered protein intake more closely. Received for publication April 14, 1958. METIIODS 1 Supported by the VA Clinical Investigator Program, by Public Health Service Grant A 1596 and by The subjects were men between 26 and 50 an American Heart Association Grant. years of age. Eight of these were volunteer 2 Reported in part at the 14th Annual Meeting of the American Federation for Clinical Research, May 5, house staff physicians and three were hospital I9.57. patients with no evidence of renal disease. 3 Veterans Administration Clinical Investigator. PresThe two diets, prepared by the hospital dietetic ent address: Renal and Electrolyte Section, Dept. of service, were: a normal hospital house staff Medicine, Univ. of Alabama Medical Center and VA Hospital, Birmingham, Alaba-ma. diet with a protein content of 25 % (150 gm 4 Established Investigator of the American Heart protein, 3000 Cal.), and a low protein diet with Association. a protein content of 4 % (25 gm protein, 3000 263 by 10.0.33.4 on A uust 0, 2017 http://jaysiology.org/ D ow nladed fom 264 MURDAUGH, SCHMIDT-NIELSEN, DOYLE AND O’DELL Volume 13 TABLE I. GLOMERULAR FILTRATION RATE, ML/MIN/I.73 M2 BSA 30and 6o-minute intervals. The collections of urine by free voiding would decrease the acSubj. 25”/0 Protein Diet