Parenteral nutrition with essential amino acids in pretransplantation anephrics.

The effect of intravenous hyperalimentation with essential amino acids and hypertonic dextrose on nitrogen metabolism, total body urea and creatinine was studied in 16 patients with end-stage renal disease prior to and after bilateral nephrectomy, splenectomy and appendectomy. Parenteral essential amino acids and hypertonic dextrose are effective in lowering blood urea nitrogen in anephric patients who are incapable of improving renal function. The inclusion of essential amino acids in hypertonic dextrose increases nutritional value far beyond that which can be attributed to the caloric concentration of the amino acids themselves.     

Total parenteral nutrition in the management of acute renal failure.

Malnutrition is frequently present in patients with acute renal failure and may affect morbidity and mortality in this condition. When adequate nourishment cannot be given through the gastrointestinal tract, total parental nutrition with amino acids and hypertonic glucose may have beneficial results. Total parenteral nutrition has been reported to stabilize or reduce serum urea nitrogen, potassium and phosphorus levels, improve wound healing, enhance survival from acute renal failure, and possibly increase the rate of recovery of renal function. The optimal composition of the total parenteral nutrition infusate is unknown. Preliminary results of a double-blind study are reported in which one man received hypertonic glucose alone, two received glucose with essential amino acids (21 g/day), and three received glucose with essential (21 g/day) and nonessential (21 g/day) amino acids. All infusates were isocaloric. No differences were observed in serum urea nitrogen levels, serum urea nitrogen/creatinine ratios or urea appearance rates. Nitrogen balance was negative in all patients. The ratio of essential amino acids/nonessential amino acids were higher and the tyrosine/phenylalanine ratios were lower in plasma in the two patients receiving glucose with essential amino acids. No patient survived the hospitalization. In view of the markedly negative nitrogen balance frequently observed in these and earlier studies, the use of a different composition or quantity of amino acids, a higher energy intake, and anabolic hormones deserve further investigation.     

Complications of essential amino acid hyperalimentation in children with acute renal failure

The metabolic effects of intravenous hyperalimentation, using an essential amino acid (EAA) and glucose solution, were evaluated in 2 children with acute renal failure. Hyperammonemia and hyperchloremic metabolic acidosis associated with elevated plasma methionine and depressed plasma citrulline, ornithine, arginine, and histidine levels complicated the nutritional therapy. Initial infusion of a complete amino acid (CAA) solution was not associated with these aberrations and reintroduction of a CAA solution after the EAA trial resulted in a progressive amelioration of or complete recovery from these metabolic disturbances. It is likely that the hyperammonemia was due to an arginine deficiency, while excess methionine and presumably sulfate production may have contributed to the hyperchloremic metabolic acidosis in these two children.     

The effect of different intravenous nutritional regimens on renal function during acute renal failure in the rat

Acute renal failure in the surgical patient is accompanied by a state of hypermetabolism and increased catabolism. Nutritional therapy is therefore directed at the preservation of body cell mass and protein synthesis for repair of wounds and damaged renal tubuli and for maintenance of host defense mechanisms. We examined the effect of two levels of protein intake (18.4 +/- 1.4 and 30.8 +/- 2.4 mg N/100 g BW/day) and three different amino acid formulations (Freamine III, Nephramine, and a made-up mixture of Nephramine + Freamine HBC) on renal function following mercury chloride-induced acute renal failure in the rat. All animals suffered severe renal failure manifested by increased plasma urea and creatinine levels, decreased creatinine clearance, and increased fractional excretion of sodium. On day 4 of acute renal failure, rats receiving low dose amino acids had better-preserved renal function than those receiving high dose amino acids. However, the type of solution infused did not affect recovery of renal function.     

Effects of an anabolic steroid on plasma amino acids, proteins, and body composition in patients receiving intravenous hyperalimentation

In this controlled trial we have studied the effect of anabolic steroid on ill surgical patients receiving intravenous hyperalimentation. Body composition, plasma proteins, and amino acids were compared in each of two groups of 12 patients before and after 14 days of intravenous feeding. The patients in one group were given 100 mg of nandrolone decanoate at the commencement of study and again one week later. Body weight, muscle (AMC), plasma transferrin, prealbumin, and retinol-binding protein were increased comparably in both groups. An apparent gain in total body nitrogen was not significant. However, anabolic steroid caused greater gain of water requiring a more liberal use of diuretics, but prevented the gains of fat, triglyceride and insulin that occurred in the control group. Most plasma amino acids increased due to intravenous hyperalimentation but decreased in patients given anabolic steroid. It is concluded that in patients who may be in the catabolic phase of recovery anabolic steroid probably enhances amino acid and water uptake by tissues and increases the utilization of fat but, does not promote any greater increase in "visceral" proteins than during intravenous hyperalimentation alone.     

Total plasma clearance of intravenous essential amino acids: evidence of abnormal metabolism of amino acids in chronic renal failure

The total plasma clearance of essential amino acids was studied in 9 non-dialyzed patients with stabile chronic renal failure and 20 healthy young adult volunteers after a bolus infusion of 0.28 g amino acids per kg of body weight in a solution containing essential L-amino acids in the proportions suggested by Rose and supplemented by L-histidine. After the infusion, the plasma concentrations of amino acids were observed for 6 hr. The pharmacokinetic analysis was performed by a polyexponential parameter estimate computer program, capable of analyzing up to five-compartment models. Wide individual variation in the capability to clear the given amino acid load from the plasma was observed. Expressed as a fraction of the sum of the total plasma clearances of the infused amino acids, the total plasma clearance of valine and phenylalanine had decreased in renal failure while that of histidine had increased. These alterations reflect the complex disorder of the protein metabolism and the observations may be of help in designing optimal nutritional regimens in renal failure.     

Low protein diet and ketosteril in predialysis patients with renal failure

After a short review of the contemporary understanding of amino acid supplementation to low protein diets in patients with uremia we present the results of administration of ketosteril in 20 low-protein-diet patients on such a diet. MATERIAL AND METHODS: Twenty patients (10 men and 10 women) with stable II and III stage chronic renal failure were assigned to a low protein diet (protein up to 40 g/day). Ketosteril (6 tablets a day) were added to the diet. Some of the basic markers of protein metabolism and nitrogen balance were followed. RESULTS: No evidence of deteriorated protein synthesis was found in the therapy thus administered. Serum urea and creatinine values did not change and even tended to decrease. Glomerular filtration was found to increase insignificantly more markedly in the patients with renal failure in the early stages. CONCLUSIONS: A low protein diet with increased content of essential amino acids and their keto-analogues does not deteriorate the nitrogen balance of patients with chronic renal failure. By adding essential amino acids and keto-analogues a normal protein metabolism is maintained in spite of the reduce intake of protein substances with the diet. Supplementation of the diet of chronic renal failure patients with essential amino acids and keto-analogues allows a considerable reduction of the protein intake to be achieved which brings about reduction of glomerular hyperfiltration which actually retards the progression of renal failure and improves its short-term prognosis.     

Protein turnover, ureagenesis and gluconeogenesis

The major processes discussed below are protein turnover (degradation and synthesis), degradation into urea, or conversion into glucose (gluconeogenesis, Figure 1). Daily protein turnover is a dynamic process characterized by a double flux of amino acids: the amino acids released by endogenous (body) protein breakdown can be reutilized and reconverted to protein synthesis, with very little loss. Daily rates of protein turnover in humans (300 to 400 g per day) are largely in excess of the level of protein intake (50 to 80 g per day). A fast growing rate, as in premature babies or in children recovering from malnutrition, leads to a high protein turnover rate and a high protein and energy requirement. Protein metabolism (synthesis and breakdown) is an energy-requiring process, dependent upon endogenous ATP supply. The contribution made by whole-body protein turnover to the resting metabolic rate is important: it represents about 20 % in adults and more in growing children. Metabolism of proteins cannot be disconnected from that of energy since energy balance influences net protein utilization, and since protein intake has an important effect on postprandial thermogenesis - more important than that of fats or carbohydrates. The metabolic need for amino acids is essentially to maintain stores of endogenous tissue proteins within an appropriate range, allowing protein homeostasis to be maintained. Thanks to a dynamic, free amino acid pool, this demand for amino acids can be continuously supplied. The size of the free amino acid pool remains limited and is regulated within narrow limits. The supply of amino acids to cover physiological needs can be derived from 3 sources: 1. Exogenous proteins that release amino acids after digestion and absorption 2. Tissue protein breakdown during protein turnover 3. De novo synthesis, including amino acids (as well as ammonia) derived from the process of urea salvage, following hydrolysis and microflora metabolism in the hind gut. When protein intake surpasses the physiological needs of amino acids, the excess amino acids are disposed of by three major processes: 1. Increased oxidation, with terminal end products such as CO? and ammonia 2. Enhanced ureagenesis i. e. synthesis of urea linked to protein oxidation eliminates the nitrogen radical 3. Gluconeogenesis, i. e. de novo synthesis of glucose. Most of the amino groups of the excess amino acids are converted into urea through the urea cycle, whereas their carbon skeletons are transformed into other intermediates, mostly glucose. This is one of the mechanisms, essential for life, developed by the body to maintain blood glucose within a narrow range, (i. e. glucose homeostasis). It includes the process of gluconeogenesis, i. e. de novo synthesis of glucose from non-glycogenic precursors; in particular certain specific amino acids (for example, alanine), as well as glycerol (derived from fat breakdown) and lactate (derived from muscles). The gluconeogenetic pathway progressively takes over when the supply of glucose from exogenous or endogenous sources (glycogenolysis) becomes insufficient. This process becomes vital during periods of metabolic stress, such as starvation.     

Effects of catabolic stress in acute and chronic renal failure

The degree of catabolism was studied in a group of seven patients with postsurgical acute renal failure, and net protein catabolism of 43.1 to 927 g/day. In 70% of a group of 30 patients with stable chronic renal failure receiving and 18 g high biological value protein diet, urea synthesis was equivalent to what could be accounted for by the protein content of the food. This equivalence was not found in studies in both adults and children who were treated for catabolic chronic renal failure. Data obtained show the superiority of feeding essential amino acids with an adequated caloric supply. The need for studies aimed at adapting the uremic patient to protein depletive mechanisms is strongly stressed.     

Total Parenteral Nutrition in Experimental Uremia: Studies of Acute and Chronic Renal Failure in the Growing Rat

The effects of total parenteral nutrition (TPN) on experimental acute and chronic renal failure were studied with special reference to age in the rat. TPN prolonged survival in acute renal failure. The young experimental animals benefitted more from the TPN. The accumulation of urea in the body was inhibited during TPN. In chronic renal failure, the low nitrogen TPN with essential amino acids as the source of nitrogen had no advantages over a regular diet fed ad libitum. Instead the TPN-rats had a markedly less positive nitrogen balance than the uremic and healthy controls. This difference was accentuated in the rapidly growing young animals. The results of this study suggest that TPN has a crucial role in the treatment of acute renal failure at an early age and are against the use of low protein diets in chronic renal failure if rapid growth is expected. (Journal of Parenteral and Enteral Nutrition 8 :427–432, 1984)     

Does nutritional intervention in protein-energy malnutrition improve morbidity or mortality?

Although there is an association between malnutrition and a poor clinical outcome, it does not necessarily follow that providing nutrients to such patients will improve the outcome. In fact, a number of prospective randomized controlled trials have not been able to demonstrate that nutritional support does, in general, improve morbidity or mortality. Very few such trials have been performed in patients with renal disease. Three studies in patients with acute renal failure have suggested that patients receiving parenteral nutrition using essential amino acids as the nitrogen source have better outcomes than do patients receiving equicaloric amounts of glucose, but these studies cannot exclude the possibility that the intravenous infusion of high concentrations of dextrose is detrimental. Small studies have suggested that the provision of perdialytic nutrient infusions or enteral nutrient supplements can improve measurements of nutritional status, but none of these trials described the effect of the nutritional intervention on morbidity or mortality. Two small trials have raised the possibility that supplemental ketoacids may retard the progression of chronic renal failure. There is a need for large randomized controlled trials to establish or refute the efficacy of nutritional support in renal disease. Such trials should include a control group that is not receiving any nutritional support.     

Blood and urinary amino acids in children receiving total parenteral nutrition

Plasma concentrations and urinary outputs of amino acids were estimated in nineteen patients receiving intravenous hyperalimentation to evaluate the adequacy of dosage and composition of the infusates for the maintenance of normal blood concentrations of essential amino acids. The use of high concentrations of branched chain amino acids seems to be appropriate for valine and isoleucine but not for leucine. The high concentration of cysteine in the infusates used induces a very high urinary excretion of cysteine and cystine and are ineffective to bring the decreased plasma cystine levels back to normal.     

Plasma proteins in patients receiving intravenous amino acids or intravenous hyperalimentation after major surgery.

Eleven plasma proteins were compared for each of three groups of 10 closely matched patients before and 15 days after rectal excision who were receiving an addition to oral diets the following parenteral solutions by central venous catheter: 1) no hyperalimentation, 2) hypertonic glucose plus amino acids, or 3) amino acids alone. Plasma transferrin, prealbumin, and retinol-binding protein were normal before surgery in all but seven patients. Postoperatively, concentrations were decreased, but were restored to normal after full hyperalimentation whereas they were significantly less and lower than normal in controls and patients receiving amino acids. Acute phase proteins were higher than normal before surgery and also 15 days later. Lower values in patients receiving hyperalimentation were mainly due to hydration compared with higher values in the other groups caused by the higher incidence of sepsis. It is concluded that full hyperalimentation after major surgery restores "visceral" proteins more rapidly than by infusion of amino acids alone and is associated with fewer clinical complications.     

Review: mechanisms for abnormal protein metabolism in uremia

Loss of protein stores, reflected by negative nitrogen balance and accelerated accumulation if nitrogenous breakdown products, is an important factor in the morbidity of chronic renal failure and the high mortality rate of acute renal failure. Low protein intake intensifies the suppressed protein synthesis that results from impaired insulin-stimulated protein anabolism. The metabolic acidosis of uremia contributes to tissue loss, both by increasing muscle protein degradation, and by raising the requirements for essential amino acids. Correcting metabolic acidosis improves the nitrogen balance and reduces tissue wasting. It is important to ensure adequate nutrient intakes, rather than the low protein diet often prescribed to slow loss of renal function.     

Review: mechanisms for abnormal protein metabolism in uremia.

Loss of protein stores, reflected by negative nitrogen balance and accelerated accumulation if nitrogenous breakdown products, is an important factor in the morbidity of chronic renal failure and the high mortality rate of acute renal failure. Low protein intake intensifies the suppressed protein synthesis that results from impaired insulin-stimulated protein anabolism. The metabolic acidosis of uremia contributes to tissue loss, both by increasing muscle protein degradation, and by raising the requirements for essential amino acids. Correcting metabolic acidosis improves the nitrogen balance and reduces tissue wasting. It is important to ensure adequate nutrient intakes, rather than the low protein diet often prescribed to slow loss of renal function.     

PROTEIN SPARING PRODUCED BY PROTEINS AND AMINO ACIDS

The provision of approximately 100 g of protein orally or of amino acids by intravenous infusion results in a marked conservation of body protein as compared to similar levels of energy provided by intravenous glucose. These effects may be explained by the more marked elevation of insulin caused by the administration of glucose.     

General and specialized parenteral amino acid formulations for nutrition support

Advances in the understanding of amino acid metabolism and of the interaction of amino acids with skeletal muscle, liver, brain, and other tissues have led to refinements of parenteral amino acid solutions. Clinical situations may dictate the use of specific amino acid formulations. Branched-chain amino acid (BCAA) solutions may normalize aberrant amino acid profiles in patients with hepatic encephalopathy; however, controlled trials demonstrate little effect on clinical outcome, and the effectiveness in patients with acute liver failure or undergoing orthotopic liver transplantation is unproved. BCAA solutions have also been tried in septic and severely stressed patients with equivocal results. Renal failure has been treated with essential amino acid solutions, yet low-dose standard amino acid formulations are probably equally effective. Pediatric preparations have been tailored to "normalize" amino acid profiles to those of healthy term, breast-fed neonates. Recent studies suggest that premature infants receiving these formulations may achieve intrauterine growth rates, although the effect on long-term outcome is unknown. Glutamine may be essential for the preservation of intestinal mucosal structure and function; further study is indicated to determine the necessity of adding glutamine to parenteral amino acid solutions. Recently, amino acid infusions have been associated with enhanced ventilatory drive, possibly via stimulation of central ventilatory mechanisms. A variety of other side effects have been documented, including acidosis, hyperammonemia, hypercalciuria, and possibly bone disease and hepatotoxicity. Further understanding of the metabolism of intravenous infusion of amino acids is necessary to provide optimal nutritional protein support. Because full information regarding the complex effects of intravenous substrates is lacking, special amino acid formulations must be used with caution.     

Effect of glucose and/or branched chain amino acid infusion on plasma amino acid imbalance in chronic liver failure

The characteristic amino acid pattern observed in chronic liver failure with high aromatic and low branched chain amino acid levels is considered to be consequent to increased muscle protein catabolism. The main catabolic stimulus has been attributed to hyperglucagonemia and to a reduced insulin/glucagon molar ratio. Intravenous administration of a solution containing branched chain amino acids and glucose to patients with chronic liver cirrhosis rapidly normalizes the plasma amino acid pattern. This effect may result from either a change in the insulin/glucagon ratio, induced by glucose, or from the anticatabolic influence of branched chain amino acids on muscle protein turnover. To discriminate between these two possibilities, a crossover study was carried out to determine the effect of a 24-hour infusion of either glucose alone, or glucose plus branched chain amino acids, in seven patients with chronic liver failure. Blood glucose, insulin, glucagon, free fatty acids, and amino acid levels were determined. Branched chain amino acids were much more effective than glucose (p less than 0.01) in decreasing the levels of aromatic amino acids. Conversely, the insulin, glucagon, and free fatty acid levels with glucose alone were not altered with the addition of branched chain amino acids. These findings suggest an anticatabolic effect of branched chain amino acids on muscle protein turnover and suggest that factors other than insulin and glucagon may be responsible for the characteristic plasma amino acid pattern present in chronic liver failure.     

Effect of a new amino acid solution on nutritional status and nitrogen metabolism in rats with chronic renal failure undergoing hyperalimentation

We studied the effects of the new amino acid solution MRX-III on the nutritional status and nitrogen metabolism of rats with chronic renal failure (CRF) in comparison with those of a general amino acid solution (MPR-F). The essential amino acids/non-essential amino acids ratio was 3.21 for MRX-III and 1.09 for MPR-F. Rats with CRF, induced by 7/8 renal ablation, were divided into 6 groups of 8 rats each receiving total parenteral nutrition (TPN) containing MRX-III or MPR-F at a non-protein calorie/nitrogen ratio (Cal/N) of 300, 600 or 900 for 7 d. The rats were infused with test solutions containing the same amounts of non-protein calories. The cumulative nitrogen balance, as a nutritional index, in the MRX-III group was significantly higher than that in the MPR-F group at the Cal/N of 600 or 900, and the plasma albumin level at the Cal/N of 300. The plasma transferrin levels at the Cal/N of 900 in the MRX-III groups were significantly higher than those in the corresponding MPR-F groups. At all Cal/N, the MRX-III groups showed low levels of blood urea nitrogen and urinary excretion of ammonia and urea nitrogen as compared with the MPR-F groups at the same Cal/N. The plasma amino acid concentration profiles in the MRX-III groups after TPN showed greater similarity to that in the Normal group as compared with the profiles in the corresponding MPR-F groups. No aggravation of renal failure was observed in any TPN groups during TPN. These results indicate that, in rats with CRF undergoing hyperalimentation, the effects of MRX-III on the nutritional status and nitrogen metabolism are superior to those of the general amino acid solution, MPR-F. It is suggested that MRX-III could safely provide adequate amounts of nitrogen during hyperalimentation.     

Nutrition disorders during acute renal failure and renal replacement therapy

The physiological and biological modifications related to acute renal failure in critically ill patients, including the current use of continuous renal replacement therapies, have dramatically changed the type and importance of the metabolic and nutrition disturbances observed during treatment of renal failure. This review summarizes the current knowledge and makes recommendations for the daily nutrition management of these patients. The filtration of water-soluble substances of low molecular weight by continuous hemodiafiltration results in significant losses of glucose, amino acids, low-molecular-weight proteins, trace elements, and water-soluble vitamins. The losses of these macronutrients and micronutrients should be compensated for. During continuous renal replacement therapy, the daily recommended energy allowance is between 25 and 35 kcal/kg, with a ratio of 60%-70% carbohydrates to 30%-40% lipids, and between 1.5 and 1.8 g/kg protein. Providing energy 25-35 kcal/kg/d with a carbohydrate/lipid ratio of 60-70/30-40 and protein 1.5-1.8 g/kg/d is recommended during continuous renal replacement therapy. Supplemental vitamin B(1) (100 mg/d), vitamin C (250 mg/d), and selenium (100 mcg/d) are also recommended.