Protein catabolism in acute renal failure.
There is no doubt that acute renal failure (ARF) is associated with enhanced protein breakdown. It has been shown that protein split products can be measured in plasma samples of these patients. On the other hand, ARF frequently occurs in conditions of increased metabolic stress which leads to enhanced protein catabolism. Muscle wasting, loss of lean body weight, and a negative nitrogen balance result in malnutrition which considerably increases morbidity and mortality. Besides the accumulation of uremic toxins, several other factors are involved in the accelerated proteolysis in ARF. Metabolic acidosis appears to be one of the major catabolic factors in chronic renal failure, and probably in ARF as well. Insulin resistance, which is commonly attributed to uremia, also increases protein degradation. However, this derangement of carbohydrate metabolism is not directly accessible to therapy, in contrast to acidosis, which can be easily corrected by bicarbonate administration. There is further evidence that glucocorticoid excess contributes to the enhanced muscle proteolysis in ARF. Moreover, several studies have demonstrated that only in the presence of both glucocorticoids and acidosis could proteolysis occur. Investigation of the cellular mechanism by which muscle proteins are degraded indicates the importance of the cytosolic, soluble ATP- and ubiquitin-dependent proteolytic system. Successful treatment of various catabolic conditions with recombinant human growth hormone and insulin-like growth factor-I seems to be a promising strategy in severely catabolic patients with ARF. Anticytokine therapy appears to be another promising treatment in the course of catabolic illness due to sepsis; however, clinical application is still in its infancy.