Figure 188

Protein catabolism in acute renal failure (ARF): contributing factors. The causes of hypercatabolism in ARF are complex and multifold and present a combination of nonspecific mechanisms induced by the acute disease process and underlying illness and associated complications, specific effects induced by the acute loss of renal function, and, finally, the type and intensity of renal replacement therapy.

A major stimulus of muscle protein catabolism in ARF is insulin resistance. In muscle, the maximal rate of insulin-stimulated protein synthesis is depressed by ARF and protein degradation is increased even in the presence of insulin [9].

Acidosis was identified as an important factor in muscle protein breakdown. Metabolic acidosis activates the catabolism of protein and oxidation of amino acids independently of azotemia, and nitrogen balance can be improved by correcting the metabolic acidosis [13]. These findings were not uniformly confirmed for ARF in animal experiments [14].

Several additional catabolic factors are operative in ARF. The secretion of catabolic hormones (catecholamines, glucagon, glucocorticoids), hyperparathyroidism which is also present in ARF (see Fig. 18-22), suppression of or decreased sensitivity to growth factors, the release of proteases from activated leukocytes—all can stimulate protein breakdown. Moreover, the release of inflammatory mediators such as tumor necrosis factor and interleukins have been shown to mediate hypercatabolism in acute disease [1, 2].

The type and frequency of renal replacement therapy can also affect protein balance. Aggravation of protein catabolism, certainly, is mediated in part by the loss of nutritional substrates, but some findings suggest that, in addition, both activation of protein breakdown and inhibition of muscular protein synthesis are induced by hemodialysis [15].

Last (but not least), of major relevance for the clinical situation is the fact that inadequate nutrition contributes to the loss of lean body mass in ARF. In experimental animals, starvation potentiates the catabolic response of ARF [7].

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