Effects of reduced renal function and dietary protein on muscle protein synthesis

We describe a rat model of renal failure that separates catabolic and anabolic states from each other. Muscle protein synthesis was compared during the anabolic period between sham (S) operated and renal failure (RF) rats that were fed different levels of dietary protein. Male rats weighing between 60 and 80 g first had a partial left nephrectomy and then were given a tryptophan deficient diet from four to six days to induce weight loss. On the second day of the diet either a renal decapsulation (S rats) or a simple right nephrectomy (RF rats) was done to enhance the catabolic response in both and to induce renal failure in the RF rats. Following the period of feeding the deficient diet, both groups were fed a nutritionally complete 14, 17, 20 or 30% protein diet for three to five days. This induced a brisk anabolic response as measured by weight gain. Differences in body weight between the S and RF rats after three to five days on the repletion diet generally was less than 10%. The rats then were fasted overnight, fed a standard meal and muscle protein synthesis (Sm%) was measured two hours post-feeding. Sm% was estimated from the incorporation of ³H phenylalanine (PHE) into muscle 10 minutes following the i.v. injection of ³HPHE (25 μCi/100 g body wt) with carrier PHE to flood all the precursor amino acid pools. Weight loss in the catabolic phase was greater and the net weight gain for the two phases was less in the RF group. Overall, renal failure resulted in a significant reduction in Sm% (P < 0.001). When Sm% for each S and RF rat, expressed as percent of the average of the S group for that study, was compared with the reciprocal of serum creatinine (1/S_Cr) for that rat a curvilinear relationship was observed. Sm% in RF rats whose S_Cr values were between 0.6 and 1.0 mg/dl did not differ from the S rats. Those with values >1.0 mg/dl showed a definite decrease in Sm%. We conclude that the anabolic response to a given meal as measured by Sm% during nutritional rehabilitation was depressed when the renal function decreased to 30% of normal. There was a tendency in the RF rats on the high protein diet to depress Sm% further, however, this finding was inconclusive.