Renal Tubular Excretion of Urea in Kangaroo Rats1

I N PREVIOUS work, it was found that the ‘osmotic ceiling’ in the urine from the desert rodents Heteromyidae is exceptionally high compared with the osmotic ceiling in urine from other mammals. This mechanism is of importance to water conservation. The general objective of the further investigations was to find in what respects the function of the heteromyid kidney differs from that of other mammalian kidneys. The emphasis of the present study was upon the demonstration of tubular excretion of urea, but information concerning glomerular filtration rate and salt excretion has also been obtained. As described in previous papers (I-3), the heteromyids are able to excrete a urine with urea concentrations up to 3.8 M ( 23yO). These high concentrations of urea in the urine were found in animals with plasma urea concentrations around IO mM. This means that the urine was about 400 times as concentrated with respect to urea as the plasma. Such high urine/plasma (U/P) concentration ratios have not been found in other mammals. In man maximum urea U/P ratio is about 170 (4), in dog it is about 220 (s), and in white rats we have found values up to 200. The high urea U/P ratios in the heteromyids could be a result of: I) high tubular reabsorption of water, 2) low permeability of the tubular wall to urea, 3) active tubular excretion of urea. Tubular excretion of urea has not been demonstrated in other mammals, but it has been found in the frog by Marshall (6) and Walker and Hudson (7), and in the aglomerular fish by Grafflin (8). The tubular excretion of urea seemed to the author the most likely of the three possibilities, and attempts were made to establish conditions that would be optimal for the demonstration of the hypothetical tubular excretion. The demonstration would depend on the finding of urea clearances higher than simultaneous inulin clearances. This could probably best be accomplished by increasing the diuresis and thereby decreasing the back diffusion of urea, and also, if possible, by increasing the tubular excretion of urea. In Berliner and Kennedy’s work with tubular excretion of potassium (9), it was found that potassium excretion could be increased upon repeated oral administration of potassium salts over a period of time. The possibility suggested itself that tubular excretion of urea might be increased in a similar way, i.e. by the administration of a high protein diet over a period of time. The experiments reported on the following pages show that the urea/inulin clearance ratio is increased in heteromyids maintained on a high protein diet. Under such conditions urea/inulin clearance ratios higher than unity were found repeatedly.