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During the past 6 years we have observed that, in children with the nephrotic syndrome, the urea clearance is not infrequently increased for periods of 1 or more months to 140 per cent or more of the average clearance of normal children of similar age and size. The phenomenon has occurred with the same frequency in both sexes. In a group of 33 nephrotic children all less than 10 years of age who were admitted to the Hospital, we have seen this type of elevation in 14 (or 42 per cent) of the patients. In 6 of the 14 patients the elevation has persisted for a period of at least 6 months; in 1 of our nephrotic children the urea clearance has been consistently elevated to between 200 and 300 per cent of normal for 6 years. These nephrotic children have been found by Farr (1) to show also a degree of lability of the urea clearance not noted in normal adult man (2) or, in our experience and in that of others, in children or adults (3) with decreased urea clearances. When the dietary protein was reduced from the optimum intake of 3 grams per kilo to 1 gram or less, the urea clearance showed a parallel fall. In contrast to our young children, only 2 out of a group of 54 nephrotic adults and children over 10 years of age observed in this Hospital have shown high clearances; these were aged 11 and 18 years. The mechanism of this high urea clearance in nephrotic children has not been explained. In the present study we have sought to determine whether the increased urea clearance is accompanied by a similar increase in the inulin clearance, which is believed to equal the volume of the glomerular filtrate (4). We have also determined the ratios of inulin clearance to urea clearance and to creatinine clearance in these patients, and compared them with the same ratios in nephrotic children with diminished urea clearances, and in children who have recovered from acute nephritis Patients studied and experimental procedures followed The patients studied in our experiments were 3 nephrotic children (R. Q., S. G., R. M.) with high urea clearances, 2 nephrotic children (J. C., S. W.) and 1 nephrotic adult (A. C.) with low urea clearances and, as controls with normal renal function, 2 children who had recovered from acute hemorrhagic Bright's disease. Of the 3 patients in the high clearance group, 1, R. M., had a urea clearance consistently elevated to above 140 per cent of normal; the other 2 patients had urea clearances always above 100 per cent of normal and frequently above 140 per cent. All the nephrotic patients exhibited proteinuria and hyperlipemia and had plasma albumin levels below 2.5 grams per 100 cc. Edema had been present previously in each case but was observed only in S. G. at the time of these experiments. Detailed laboratory and clinical data on 4 of these patients (R. Q., S. G., J. C., S. W.) have been published elsewhere (5, 6). For several months previous to these experiments all of the patients except B. D. and A. C. had been fed a diet which provided 3 grams of protein per kilogram of ideal body weight. The daily intake of sodium chloride was 1 to 1.5 grams. All tests were performed under fasting conditions; the subjects were kept in bed during the clearance periods. Preceding and during the experiments, from 1 to 2 liters of water were administered orally to maintain an adequate flow of urine. The patients were not catheterized. After 2 or 3 control periods, each of approximately 1 hour's duration, during which specimens of urine and a single blood sample were obtained for the determination of urea and " endogenous " creatinine clearances, creatinine was administered orally. One hour later a single injection of inulin, prepared as a 10 per cent solution in 0.85 per cent sodium chloride solution,' was administered intravenously during the course of 15 to 20 minutes. The quantities of creatinine and inulin given varied in the individual experiments as shown in Tables I, II and III. Thirty to 60 minutes following the injection of inulin, urine collections were resumed for the determination of simultaneous inulin, "exogenous" creatinine, and urea clearances. The duration of these latter periods of urine collection varied usually from 30 to 60 minutes and was determined by the patients' desire to void. Venous blood samples were obtained at the beginning and end of each period.

THE RELATION OF HIGH AND LOW UREA CLEARANCES TO THE INULIN AND CREATININE CLEARANCES IN CHILDREN WITH THE NEPHROTIC SYNDROME