ALBUMIN METABOLISM IN AMINONUCLEOSIDE NEPHROTIC RATS.

Abstract

Abstract Aminonucleoside nephrotic and normal control rats were injected with biologically purified homologous plasma albumin labeled with I 131 , and the decay of plasma albumin specific activity and urinary excretion of protein and non-protein-bound I 131 were measured. The size of the vascular and extravascular albumin pool and the rates of albumin breakdown and total loss were obtained from these data. The rates of catabolism and loss were calculated by 4 independent methods: (1) by kinetic analysis based on the assumption of a system consisting of 1 vascular and 1 extravascular compartment, (2 and 3) by 2 independent methods based on the urinary I 131 excretion and plasma specific activity after distribution equilibrium, and (4) from the recoveries of urinary albumin and free and protein-bound I 131 in the urine. In normal rats, the mean catabolic rate obtained by method 1 was 3.2 mg. per hour per 100 grams of rat weight, and by methods 2 and 3, 3.9 mg. per hour per 100 grams. In nephrotic rats, the values for total loss determined by methods 2, 3, and 4 were in good agreement but differed greatly from that calculated by method 1 (kinetic analysis). The value obtained by methods 2, 3, and 4 was from 1.5 to 2.5 times higher than that obtained from 1. The values obtained by the latter procedure were less than the actual albumin recovered in the urine, and it appears that the kinetic analysis is based on assumptions not valid in nephrotics. A Ibuminuria in the nephrotic rats ranged from 5 to 12 mg. per hour per 100 grams and catabolism from 1 to 4 mg. per hour per 100 grams. The fractional rates of catabolism ranged from 2.5 to 8 per cent of the circulating albumin per hour. There was a positive correlation between catabolism and albuminuria. It is proposed that in animals with heavy albuminuria, albumin breakdown occours by 2 processes, one in the kidney and another in extrarenal tissues. The breakdown in kidneys is minor below an albuminuria threshold of about 5 mg. per hour per 100 grams, but above this threshold it increases with urinary albumin loss. In rats with extensive albuminuria, renal breakdown of albumin is the major catabolic process.