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The clinical status of patients with acute renal failure (ARF) varies greatly. Some individuals have only mild or moderate ARF or may have only mild perturbations of their metabolic status. Other patients exhibit a severe reduction in renal function with oliguria or anuria. Depending upon their comorbid conditions, ARF patients may be among the most hypercatabolic patients in the hospital. Clinical trials have not clearly shown a beneficial effect of nutrition support on morbidity or mortality in patients with ARF, although limitations in sample size and experimental design and inclusion of patients with widely disparate clinical conditions may have contributed to the difficulty in demonstrating benefits. Several recent therapeutic approaches that have been studied either in experimental animals with ARF or in small numbers of humans with ARF hold promise for improving clinical outcome. Continuous arteriovenous or venovenous hemofiltration with or without dialysis is such a therapy. In comparison to intermittent hemodialysis this former treatment more safely removes large quantities of water and solutes from critically ill patients with unstable hemodynamics and allows them to receive rather large quantities of nutrients, including amino acids. Also promising are studies in experimental animals with ARF which indicate that several growth factors may accelerate the recovery of renal function. In rats with ARF, insulin-like growth factor 1 both enhances recovery of renal function and suppresses their enhanced catabolism. For most patients with ARF requiring nutrition support, evidence suggests that both essential and nonessential amino acids should be employed. However, there appears to be a therapeutic role for small quantities of essential amino acids, without nonessential amino acids, in selected patients. Data support the importance of proactive measures to prevent fluid and electrolyte imbalances in patients with ARF.

Background: Numerous animal studies have demonstrated intestinal villus atrophy occurs when luminal nutrition is withheld and total parenteral nutrition (TPN) is provided. Intestinal morphologic and functional changes have not been well studied in humans during TPN., Methods: Eight normal volunteers were hospitalized in the Clinical Research Center for 3 weeks. The subjects received TPN as an exclusive means of nutritional support for 14 days followed by 5 days of enteral refeeding with either a standard or a glutamine and arginine-supplemented formula. Endoscopic jejunal biopsies were taken before and after TPN and after enteral refeeding. Intestinal morphology was examined by light and transmission electron microscopy. Mucosa DNA, RNA, and protein concentrations were measured. Lactose breath hydrogen and intestinal permeability testing (urinary lactulose and mannitol excretion after an oral dose) were performed before and after TPN and after enteral refeeding., Results: Total mucosal thickness decreased after TPN (645 +/- 19 to 512 +/_ 19 microns, p = .003) and increased significantly towards baseline after enteral refeeding (575 +/- 19 microns, p = .04). The change was related solely to villus height; crypt depth was unaffected. Villus cell count decreased from 179 +/- 15 to 163 +/- 12 after TPN (p = .03) and increased after enteral refeeding to 176 +/- 21 (p = .06). Crypt cell count was unaffected by TPN or refeeding. A nonsignificant decrease in the mitotic index after TPN was seen. Intracellular edema developed during TPN and resolved with enteral refeeding. The urinary lactulose-mannitol ratio increased with TPN [0.06 +/- 0.03 to 0.11 +/- 0.05 after TPN and 0.14 +/_ 0.09 after short-term enteral refeeding (p = .05)], indicating increased intestinal permeability. The urinary lactulose-mannitol ratio was significantly greater after refeeding with standard formula than the free amino acid peptide formula with glutamine and arginine (0.20 +/- 0.05, vs 0.08 +/- 0.01, p = .05). No significant differences were noted in mucosal RNA, DNA, protein, DNA-protein or RNA-DNA rations or breath hydrogen after lactose ingestion after either TPN or enteral refeeding. No significant difference in plasma glutamine was found during TPN (462.7 +/ 38.7 vs 491.8 +/- 46.1 mumol/L) or after enteral refeeding (457.3 +/- 51.4 mumol/L)., Conclusions: Intestinal morphologic and functional changes occur in human for whom TPN is the sole nutritional source, although the findings in humans are substantially less significant than observed in animal models. The loss of mucosal structure may be sufficient to cause increased intestinal permeability, the clinical significance of which remains to be defined. Enteral nutrition is important in restoring and probably preventing morphologic intestinal changes associated with TPN, and a peptide and free amino acid-based formula supplemented with glutamine and arginine may have some added role. Our findings also suggest sepsis is associated with gut adaptation rather than degradation.

Recombinant human insulin-like growth factor-1 (rhIGF-1) is currently used experimentally to treat patients with insulin-resistant diabetes mellitus, impaired growth, protein malnutrition, and osteoporosis. We report here the case of a marked transient alteration in consciousness in a healthy 22-year-old man who was given an IV infusion of a relatively low dose of rhIGF-1 for 1 hour. This individual developed the sudden onset of dizziness, nausea, coldness, air hunger, and pallor. He became unresponsive to simple questions and experienced diaphoresis, a feeling of warmth, and paresthesias. Although there was a mild fall in heart rate and blood pressure, these hemodynamic effects did not appear sufficient to cause the altered mentation. There were no changes in serum glucose, phosphorus, or potassium that could seem to account for these events. This individual recovered completely several minutes after stopping the rhIGF-1 infusion.

Background: A rat model of acute renal failure (ARF) with sepsis (ARF+S) was developed to simulate the clinical syndrome of hypercatabolic illness in patients with ARF., Methods: Sepsis was created by ligation and needle puncture of the cecum; ARF was created by left renal artery clamping and contralateral nephrectomy., Results: Two studies were performed. In study 1, rats with sham surgery, sepsis, ARF, and ARF+S were examined for 48 hours. During the first 24 hours after surgery, ARF and ARF+S rats displayed increased urea and ammonia nitrogen appearances and abnormal plasma amino acid levels. These abnormalities were exaggerated in ARF+S rats. In study 2, sham, ARF, and ARF+S rats were injected with sodium bicarbonate or normal saline. During the first 24 hours after surgery, the ARF and ARF+S rats showed an increase in urea nitrogen appearance to 210% and 293%, respectively, of sham values, which was greater than the levels that have been previously reported. Sodium bicarbonate treatment did not influence nitrogen output., Conclusions: Rats with ARF+S may be a useful model for studying catabolic patients with ARF. The lack of effect of sodium bicarbonate on nitrogen balance merits additional study.

There is growing evidence that taurine is a biologically valuable nutrient. However, there are few published data concerning the taurine content of different foods. We measured the taurine content of 29 meats, including both cooked and uncooked samples, nine dairy products, 17 infant or adult-feeding solutions and 48 plant foods (including vegetables, nuts or seeds, fruits and legumes. Taurine was detected in meats, dairy products, and infant feeding solutions but not in plant products or adult feeding solutions. Using these data, we compared calculated and measured daily taurine intakes in six defined diets. We present sample daily diets for omnivores, lacto-ovovegetarians and vegans (strict vegetarians), together with calculated taurine intakes.

Red cell and plasma amino acid concentrations were measured in nine healthy subjects, nine patients with advanced chronic renal failure, and before and after dialysis in eight patients undergoing maintenance hemodialysis. Blood was obtained after an overnight fast except for postdialysis specimens. In red cells from the chronically uremic patients and in predialysis specimens, there was increased histidine, cystine, glutamic acid, glycine, ornithine, citrulline, taurine, and N tau-methylhistidine, and an increased glycine to serine ratio. Red cell valine, tyrosine, and the ratios of tyrosine to phenylalanine and valine to glycine were decreased in the two groups. Many amino acid levels that were abnormal in red cells were also abnormal in plasma. However, several amino acids were altered in only one of these compartments. Some red cell or plasma amino acid concentrations were abnormal in the uremic or hemodialysis patients but not in both. During hemodialysis, red cell amino acids did not decrease as markedly as did the plasma concentrations. These findings indicate that in chronically uremic and hemodialysis patients there is an abnormal amino acid pattern in both red cells and plasma. Although the altered amino acid patterns in these two compartments have similarities, they are not identical.

Chronically uremic patients appear to have an increased nutritional requirement for vitamin B6, and vitamin B6 deficiency occurs frequently when such individuals do not receive supplements of this vitamin. Since manifestations of vitamin B6 deficiency in renal failure are not well defined, this study examined two aspects of the chronic renal failure syndrome which might be influenced by vitamin B6: impaired growth and progressive loss of renal function. We examined food intake, weight gain, the food efficiency ratio, degree of azotemia, and renal function in chronically azotemic rats pair-fed for 6 weeks either a vitamin B6-deficient diet or a diet containing a surfeit of vitamin B6. In the azotemic vitamin B6-deficient rats, as compared to the azotemic B6-replete rats, there was evidence of reduced appetite, decreased weight gain, a lower food efficiency ratio, increased azotemia, and a reduced glomerular filtration rate as estimated from the urea clearance or the mean of the urea and creatinine clearances. These findings suggest that vitamin B6 deficiency may contribute to decreased food intake, reduced growth, and lower renal function in animals with chronic renal insufficiency.

Classical balance techniques are a powerful, sensitive, and usually accurate technique for assessing the nutritional or metabolic response to changes in nutritional intake or to metabolic or physiological perturbations. Balances are particularly sensitive for examining transient or short-term responses to nutritional or metabolic stimuli. A major factor responsible for the precision and sensitivity of this technique is the precise control of the activities and environment of an individual during a classical metabolic balance study (eg, the carefully defined dietary intake, degree of exercise, and environmental temperature to prevent sweating); these same factors may enhance the precision and sensitivity of other metabolic or nutritional investigations that may be carried out concurrently with a balance study. Finally, for nitrogen balance studies, the measurement of nitrogen (eg, by the Kjeldahl technique) can be very accurate and sensitive. Despite these advantages, there are important limitations and errors that are inherent in the balance technique. The errors tend to overestimate intake and underestimate output, thereby leading to erroneously positive balances. These errors include losses of food on cooking and eating utensils and dishware, losses of feces or urine on toilet paper or in collection containers, and losses through sweat, exfoliated skin, hair and nail growth, saliva, menses, blood sampling, toothbrushing, semen, and, for nitrogen, from flatus and respiration. Cumulative balance measurements are particularly likely to be falsely positive. The magnitude of unmeasured losses vary among healthy individuals, with the magnitude of the nitrogen intake (for nitrogen), in altered environmental conditions (eg, with sweating), and possibly in disease states. Balance studies are also expensive and time consuming.(ABSTRACT TRUNCATED AT 250 WORDS)