Role of essential amino acids in renal failure

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In 1956 Rose and Dekker found a large amount of N-labeled urea in non-essential amino acids after feeding rats only essential amino acids and urea.1 In a landmark 1963 publication Giordano hypothesized that, if urea could be used for protein synthesis, patients with azotemia might be able to use their own urea for anabolic purposes.2 Under rigidly controlled conditions, one normal volunteer and eight patients with renal disease, six of whom were uremic, were studied while being fed a synthetic diet of carbohydrates, fats (2300 to 3100 cal/d), and 2 g of nitrogen as essential amino acids in two different formulas.2 The results of that elegant and meticulous study were astounding because patients not only sustained a reduction of azotemia but also exhibited a positive nitrogen balance and clear clinical improvement. Giordano concluded that in uremia endogenous urea might be used for protein synthesis and that azotemic patients can use their accumulated urea nitrogen for anabolic purposes, provided they consume a diet adequate in calories with nitrogen supplied by minimal amounts of essential amino acids. The use of endogenous urea, as of other body-retained nitrogenous substances, parallels a progressive clinical improvement in uremic patients. The findings of Giordano and then Giovanetti and Maggiore3 opened the way for the nutrition support and proper management of patients with chronic renal failure who under this regimen could forgo dialysis for some time while maintaining reasonable nutrition status and experiencing clinical well-being. This concept of nutritional manipulation of patients with renal failure gained renewed popularity with the advent of parenteral nutrition. Acute renal failure in hypercatabolic states, a common affliction in surgical patients, results in only 38% recovery of renal function and a meager 35% survival rate. As early as 1969 Wilmore and Dudrick, from the University of Pennsylvania, published two papers dealing with the treatment of acute renal failure with intravenous essential L-amino acids4 followed closely by two papers from Abel et al.,5 from Massachusetts General Hospital. Parenteral nutrition with hypertonic glucose and small amounts of essential amino acids resulted in a positive nitrogen balance and reduced serum levels of urea nitrogen, potassium, and phosphorus. In a 1973 landmark, prospective, randomized, double-blind study, the very first in the field of parenteral nutrition and, unfortunately, still among the very few, Abel et al. compared infusion of glucose alone with glucose plus essential amino acids in 53 patients in acute renal failure.6 Those who were given essential amino acids had lower mortality (44% survival in the glucose group versus 75% in the amino-acid group), fewer complications, and a trend toward more rapid recovery from acute renal failure. A long list of excellent, but conflicting, animal and human studies followed, with no firm conclusion as to the efficacy of essential amino acids in the treatment of acute renal failure. In a meta-analysis of the four major randomized clinical trials, Naylor found that the use of essential amino acids was associated with an absolute increase in initial survival of 24% in favor of essential amino acids, leading to the conclusion that essential amino acids are an important component in the nutritional management of patients with acute renal failure.7 In recent years the controversy has shifted to the comparison between mixtures of essential amino acids and dextrose and mixtures of balanced essential and non-essential amino acids and dextrose in patients with acute renal failure. No consensus has been reached. However, because nutrition support remains an important component of management of hypercatabolic patients with acute renal failure, a reasonable algorithm would be that, as long as patients are not dialyzed, essential amino-acid solutions seem to be superior. Once dialysis or hemofiltration can or must be initiated, nutrition support in the form of essential and nonessential amino acids should be administered. Even so, mortality rate in acute renal failure remains high in hypercatabolic surgical patients, indicating that future research efforts investigate new and probably more sophisticated modes of therapy.