circulating levels of renin and angiotensin [39]; 2) decreased peritubular hydrostatic pressure, which presumably could result from a fall in blood pressure and cardiac output. In patients with protein-calorie malnutrition, studies performed before and after protein repletion revealed a decrease in free water clearance values after correction of the protein deficit [36]. These data suggest that proximal sodium reabsorption may actually be decreased in the malnourished state. If so, most of the increased sodium retention ability observed in malnourished subjects could be the consequence of forces acting beyond the proximal tubule, presumably at the level of the ascending limb of Henle's loop and distal tubule. It is of interest that recently Grausz, Lieberman and Earley [40] have suggested a decreased sodium reabsorption in the proximal tubule in patients with the nephrotic syndrome. Taken together, these observations indicate that hypoalbuminemia by lowering peritubular oncotic pressure may indeed decrease proximal sodium reabsorption on a chronic basis and that the edemaforming state observed both in the nephrotic syndrome and in chronic protein malnutrition occurs despite depressed proximal tubular fractional reabsorption, and therefore may involve reabsorption of an excessively large fraction of filtered sodium in segments of the nephron located beyond the proximal tubule. Concentration and dilution of the urine in malnutrition. The most commonly described features of renal dysfunction in malnourished patients are polyuria and nocturia. These symptoms were described in detail in World War 1 victims by Schittenhelm and Schelecht in 1918 [411, and since then numerous observers have confirmed the increased urine volume in the malnourished state. The usual figure for 24 hours urine volume for a semistarved subject lies between 2 and 3 liters. Klahr et al [18] studied the diluting and concentrating ability of the kidney in eight malnourished adults before and after protein repletion. Three additional patients were studied during the proteindepleted state only. A defect in renal concentrating ability was present in the 11 patients with protein malnutrition studied. Urine osmolality following 14 hours of fluid deprivation [42] never exceeded 600 mOsm/kg of water in these malnourished subjects. The concentrating defect was reversible following protein repletion in the eight patients in whom this procedure was carried out. A renal concentrating defect which improves following protein repletion has also been described in malnourished children by Alleyne [6] and by McCance, Crowne and Hall [43]. Role of antidiuretic hormone in the concentrating defect. Hormonal imbalances particularly of antidiuretic hormone have been held responsible for certain alterations of renal function in malnutrition. Since concentrated urine can be elaborated in the absence of antidiuretic hormone under conditions of decreased glomerular filtration rate per nephron [44], a phenomenon present in these patients, a lack of ADH cannot be excluded as a cause of the concentrating defect of malnutrition. Consequently, we explored the renal response of malnourished adults to the administration of Pitressin during water diuresis. After establishing adequate urine flow by the oral and intravenous administration of fluids, 15 mU of aqueous vasopressin (Pitressin, Parke, Davis and Company, Detroit, Mich.) were given intravenously. Shortly after the administration of vasopressin there was a marked decrease in urine volume and free water clearance values with a concomitant increase in urine osmolality indicating a normal response to the administration of antidiuretic hormone. However, this response to the administration of exogenous antidiuretic hormone does not exclude an abnormality in the secretion of ADH from the posterior pituitary or an abnormal response of the osmoreceptors to changes in the osmolar composition of plasma. Stimulation of the neurohypophysis by intravenous nicotine administration revealed that malnourished subjects are capable of secreting endogenous ADH. Finally, the response observed when hypertonic saline solutions were administered demonstrated the integrity of the osmoreceptors and the adequacy of the posterior pituitary gland to secrete ADH as a consequence of changes in the osmolar composition of plasma. Chronic protein-calorie malnutrition 135 Fig. 3. Urine osmolality and negative free water clearance in malnourished patients before (open bars) and after (striped bars) protein repletion. Minimal urine osmolality and free water clearance (CH20). Data for minimal urine osmolality and free water clearance (C1120) in seven malnourished patients revealed a mean value of 57 mOsm per kg of water for minimal urine osmolality, a figure comparable to that observed in normal subjects. Mean free water clearance values corrected for 100 ml of glomerular filtration rate was 15.8 ml, a figure also comparable to that observed in healthy subjects. Solute free water reabsorption (T20). Measurements of T20 were obtained in four malnourished patients during mannitol diuresis and concomitant administration of vasopressin intravenously. In these patients the studies were repeated after protein repletion. The results are summarized in Fig. 3. There was a marked