clearance [26]. In Longley and Miller's series it is possible to attribute this fall to a decrease in GFR. In Nielson and Bang's patients [11], however, the fall in urea clearance seemed to depend upon tubular factors entirely, since GFR did not change. Pullman et al [10] also observed in some of their normal subjects fed a low protein diet a fall in urea clearance not accountable by a change in GFR. When the urea to inulin clearance ratios in malnourished subjects are plotted in relation to the reabsorption of water (U/P inulin ratios) it is evident (Fig. 1) that at any 132 Klahr/Alleyne SU LI 1 20 40 60 80 100 120 140 Fig. 1. The urea to inulin clearance ratio in malnourished subjects in relation to the reabsorption of Water (U/P mu/in). The solid dots represent data in malnourished subjects. The open dots (upper curve) are from the data of Shannon (Am J Physiol 122: 782, 1938). given level of fractional water reabsorption the ratio of urea to inulin clearance is markedly reduced in malnourished subjects. Indeed, some patients reabsorbed more than 90% of the filtered urea when their urine flow rate was less than 1 mI/mm. Even when 16% of the filtered water was excreted (inulin U/P=6), the clearance of urea was only 20% of the inulin clearance. Unfortunately, we have no observations on urea clearance values at U/P inulin ratios below 6, since it was difficult to increase the percent of filtered water excreted above these values. These data suggest that under conditions of protein deficiency there may be a component of active urea transport contributing to the tubular reabsorption of urea. It has been shown previously that fractional excretion of urea decreased markedly when animals were placed on a low but adequate protein diet [27, 281. In low-protein-fed sheep and rats it was observed that the renal medullary urea concentrations were higher than urea concentrations of the final urine, indicating an active transport of urea out of the collecting duct [29]. Micropuncture experiments by Clapp [30], Lassiter, Mylle and Gottschalk [311 and Ullrich, Rumrich and Schmidt-Nielsen [32] strongly suggest that in rats fed a normal protein diet the urea transport across the collecting duct wall is passive, while in rats on a low protein diet an active outward transport is superimposed. It has been also suggested that uphill transport of ui ea exists in the dog and energy for this transport is derived from anaerobic glycolysis [33]. Our data, though indirect, suggest that in man, under conditions of chronic protein deficiency, an active component for urea reabsorption may be present. We have also demonstrated recently that when malnourished man is given urea a positive nitrogen balance develops, suggesting that the nitrogen of urea may be utilized in patients with severe malnutrition [34]. Similar observations have been made in malnourished children [35]. Blood urea nitrogen and plasma creatinine levels in ma!- nutrition. Under most conditions a marked impairment in renal function can be detected by increased plasma levels of creatinine, or urea nitrogen, or both. If production of urea and creatinine is decreased, however, moderate to severe impairment of renal function might well be observed in the absence of increased plasma levels of urea nitrogen, or creatinine, or both. In patients with moderate to severe protein malnutrition, plasma levels of creatinine and urea nitrogen tend to be low despite a substantial reduction in glomerular filtration rate. Since excretion of both creatinine and urea is reduced in patients with protein-calorie malnutrition, one can conclude that the production of both of these end products is decreased in malnutrition [14]. Decreased creatinine production presumably results froma decreased muscle mass. The low urea levels probably result from decreased protein intake, decreased tissue breakdown and/or urea reutilization. During protein repletion, both BUN and plasma creatinine increase despite a concomitant increase in glomerular filtration rate. These data suggest increased entry into body fluids of both compounds during repletion. It is of interest that in children who are recovering from malnutrition urea levels may rise to values above normal. This may simply reflect the high protein intake which is usually given. Effects of malnutrition on the renal handling of sodium. In health, the body normally maintains a relatively constant volume and composition of extracellular fluid. A large and increasing number of experimental observations now support the view that volume regulation and sodium excretion are interdependent functions. There is growing evidence that sodium mass per se is not regulated directly, nor is sodium concentration. Rather, extracellular fluid volume seems to be the sodium-related parameter of body fluids that is monitored and controlled. Thus, the sodium control system, in essence, is the volume control system. Edema-forming states are characterized by the renal retention of salt and water. Thus, in the edema-forming syndromes, the rate of excretion of sodium and water fromthe body is less than the concurrent rate of acquisition. Common to all edema-forming states is the apparent need for the expansion of effective extracellular fluid volume. Edema is not a universal finding in patients with chronic protein-calorie malnutrition. The presence or absence of edema in malnourished subjects seems to