Lead metabolism in the normal human: stable isotope studies.

Kinetic and metabolic balance studies in a healthy man fed a diet normal in lead content and labeled with lead-204 indicated that approximately two-thirds of his assimilated lead was dietary in origin; the remainder was inhaled. Kinetic analysis shows that the isotopic data can be interpreted by a three-compartment model.

Oxymetholone ameliorates insulin sensitivity in maintenance hemodialysis patients: a randomized controlled trial.

AIMS: To investigate the beneficial effects of oral oxymetholone on IR in hemodialysis (HD) patients by increasing skeletal muscle function and stimulating myocyte glucose uptake and metabolism. METHODS: In a randomized, controlled double-blind study, 44 patients were randomly assigned to one of two groups: a treatment group that received oxymetholone 50 mg orally twice daily and a control group that received placebo twice daily for 24 weeks. IR was calculated by using HOMA, and dual-energy X-ray absorptiometry was used to determine body composition. All patients were encouraged to walk at least one kilometer daily and were monitored by the Barthel index activity score. RESULTS: 25 men (57%) and 19 women (43%) were studied. 23 subjects were in the control group, and 21 subjects were in the treatment group. The mean age of patients and the duration of dialysis were 43.5 +/- 9.9 years and 92.8 +/- 37.8 months, respectively. After treatment, the HOMA index and body fat mass (FM) were significantly decreased in the treatment group compared to those in the control group (10.8 +/- 16.4 vs. 3.1 +/- 4.5; p < 0.05 and 1.73 +/- 2.77 vs. 0.40 +/- 1.12 kg; p < 0.05, respectively). Concurrently, the mean change of fat free mass (FFM) in the treatment group was higher than that in the control group (3.24 +/- 1.74 vs. 0.65 +/- 1.21 kg, p < 0.05). Two patients in the treatment group experienced an elevation in serum liver enzymes (9.52%). CONCLUSION: HD patients treated with short-term oral oxymetholone showed an increase in insulin sensitivity when compared to the placebo group, and this effect depended on changes in FFM and FM.

Evidence that histidine is an essential amino acid in normal and chronically uremic man.

The requirement for dietary histidine was investigated in four normal and three chronically uremic men. Subjects lived in a metabolic unit where they were fed three isonitrogenous diets in the following order: a 40-g protein diet (28 plus or minus SD 8 days), a semi-synthetic amino acid diet deficient in histidine (35 plus or minus 2 days), and an amino acid diet which contained histidine (31 plus or minus 5 days). With ingestion of the histidine-deficient diet, nitrogen balance gradually became negative, and serum albumin decreased in six subjects. Plasma histidine fell by 82 plus or minus 6 per cent; muscle histidine decreased by 62 plus or minus 19 per cent; the hematocrit fell by 25 plus or minus 9 per cent; and serum iron rose. Subjects felt unwell, and in five cases a skin lesion consisting of fine scales, dry skin, and mild erythema developed. After administration of the histidine-repletion diet, nitrogen balance became positive in six subjects; serum albumin increased in five cases; plasma and muscle histidine rose; serum iron fell abruptly; a reticulocytosis ensued; and the hematocrit rose. The clinical symptoms and skin lesions disappeared. These observations indicate that histidine is an essential amino acid in normal and chronically uremic man. The absence of dietary histidine is associated with failure of normal erythropoiesis.

Evidence that insulin-like growth factor I increases renal plasma flow and glomerular filtration rate in fasted rats.

The mechanisms whereby growth hormone may increase renal plasma flow (RPF) and GFR are not known, but circumstantial evidence has implicated insulin-like growth factor I (IGF-I) as a mediator of this effect. This study examined whether an infusion of IGF-I will increase RPF and GFR, whether this effect occurs quickly, and if this effect is dependent on eicosanoids or peptide hormones known to affect renal function. Rats fasted for 3 d to reduce IGF-I and IGF-I plasma binding proteins were anesthetized; then the rats received an intravenous injection of 25 micrograms/kg IGF-I, and an infusion of 25 micrograms/kg IGF-I within 20 min. Controls received infusion of the vehicle. RPF (para-aminohippurate clearances), GFR (inulin clearances), renal vascular resistance (RVR), mean arterial blood pressure (MABP), plasma IGF-I, and glucose concentrations were measured repeatedly. At the end of the 20-min infusion, plasma IGF-I tended to be increased in the animals that received IGF-I (P = 0.069), but did not increase in the control rats. IGF-I induced a significant and sustained fall in RVR and rise in RPF and GFR without any change in MABP. A small, transient, but significant decrease in plasma glucose concentrations was observed during IGF-I but not during vehicle infusion. Indomethacin, but not somatostatin, blocked the renal response to IGF-I infusion. Thus, IGF-I infusion increases RPF and GFR and reduces RVR in fasted rats. This effect requires the presence of eicosanoids but does not seem to require other peptide hormones suppressed by somatostatin.

Recombinant human insulin-like growth factor-I accelerates recovery and reduces catabolism in rats with ischemic acute renal failure.

This study evaluated whether recombinant human insulin-like growth factor-I (rhIGF-I) enhances recovery of renal function and reduces catabolism in rats with ischemic acute renal failure (ARF). ARF and sham rats received subcutaneous injections of either rhIGF-I or vehicle three times daily starting 5 h after surgery. Serum creatinine and urea, which initially rose similarly in the ARF+vehicle and ARF+rhIGF-I rats, increased more slowly after commencing the rhIGF-I injections. 72 h after surgery, the ARF+rhIGF-I rats, in comparison with ARF+vehicle animals, showed significantly greater renal plasma flow and filtration fraction, a fivefold higher glomerular filtration rate, greater renal cortical IGF-I levels, increased proliferating cell nuclear antigen expression in proximal tubule nuclei and enhanced DNA synthesis in the renal cortex, corticomedullary junction, glomeruli, and tubules as demonstrated by [3H]thymidine incorporation and in corticomedullary junction tubules as determined by autoradiography. Estimated total nitrogen output (ETNO) was greater in ARF+vehicle than in ARF+rhIGF-I or sham rats throughout the study. ETNO in ARF+rhIGF-I rats returned to sham values by the second day after surgery. 72 h after surgery, protein degradation was increased and protein synthesis reduced in the epitrochlearis muscle of ARF+vehicle as compared with ARF+rhIGF-I or sham+vehicle rats. Thus, treatment with rhIGF-I starting 5 h after inducing ischemic ARF in rats increases recovery of renal function, enhances formation of new renal tubular cells, lowers protein degradation, and increases protein synthesis in skeletal muscle and reduces net catabolism.

Kinetic analysis of lead metabolism in healthy humans.

The steady state kinetics of lead metabolism were studied in five healthy men with stable isotope tracers. Subjects lived in a metabolic unit and ate constant low lead diets. Their intake was supplemented each day with 79--204 mug of enriched lead-204 as nitrate which was ingested with meals for 1--124 days. The concentration and isotopic composition of lead was determined serially in blood, urine, feces, and diet and less commonly in hair, nails, sweat, bone, and alimentary tract secretions by isotopic dilution, mass spectrometric analysis. The data suggest a three compartmental model for lead metabolism. The first compartment encompasses blood and is 1.5--2.2 times larger than the blood mass. It contains approximately 1.7--2.0 mg of lead and has a mean life of 35 days. This pool is in direct communication with ingested lead, urinary lead, and pools two and three. The second compartment is largely composed of soft tissue, contains about 0.3--0.9 mg of lead, and has a mean life of approximately 40 days. This pool gives rise to lead in hair, nails, sweat, and salivary, gastric, pancreatic, and biliary secretions. Pool three resides primarily in the skeleton, contains the vast quantity of body lead, and has a very slow mean life. Bones appear to differ in their rates of lead turnover. Within the relatively small changes in blood lead observed in the present study, the transfer coefficients between the pools remained constant.

Effects of recombinant human insulin-like growth factor I on glomerular dynamics in the rat.

This study was undertaken to investigate the mechanisms by which an infusion of recombinant human insulin-like growth factor I (rhIGF-I) increases GFR and renal plasma flow (RPF) in rats. Glomerular micropuncture studies were carried out in 14 nonstarved Munich Wistar rats and in 12 rats deprived of food for 60-72 h. Animals were given an intravenous injection and infusion of either rhIGF-I or vehicle. In both nonstarved and starved animals, the IGF-I injection and infusion increased the serum IGF-I levels, left kidney GFR, single nephron glomerular filtration rate (SNGFR), single nephron blood flow rate (SNBF), and single nephron plasma flow rate (SNPF). The increase in SNPF and SNGFR was in part due to a fall in efferent arteriolar resistance (RE); there was a tendency, not significant, for afferent arteriolar resistance (RA) to fall in comparison to controls. The increase in SNGFR was partly caused by a rise in SNPF but was primarily due to an increase in glomerular ultrafiltration coefficient (LpA) to twice the control values. The increase in LpA resulted in an increase in SNGFR because the rats operated at ultrafiltration pressure disequilibrium. Control starved as compared with nonstarved rats had lower SNGFR, SNBF, and SNPF. This reduction was due to a tendency, not significant, for both RA and RE to be higher. Decreased SNGFR in food-deprived rats resulted from a reduced SNPF, a lower glomerular transcapillary hydrostatic pressure difference (delta P), and possibly a somewhat reduced LpA. These data indicate that IGF-I increases SNGFR, SNPF, and SNBF primarily by increasing LpA and also by decreasing RE without affecting delta P. Short-term starvation lowers SNGFR, SNPF, and SNBF primarily by decreasing delta P and possibly by lowering LpA and increasing RA and RE. IGF-I reverses some of the glomerular hemodynamic effects of short-term food deprivation.

Impaired actions of insulin-like growth factor 1 on protein Synthesis and degradation in skeletal muscle of rats with chronic renal failure. Evidence for a postreceptor defect.

The actions of insulin-like growth factor 1 (IGF-1) on protein turnover and of the IGF-1 receptor (IGF-1R) were examined in skeletal muscle of rats with chronic renal failure (CRF) and sham operated (SO), pair-fed controls. Acidemia was prevented in CRF rats with NaHCO3. Serum IGF-1 and skeletal muscle IGF-1 and IGF-1 mRNA were reduced in CRF rats. Dose-response studies revealed impaired stimulation of protein synthesis and suppressed inhibition of protein degradation by IGF-1 in epitrochlearis muscle of CRF rats. Neither IGF-1 analogues with low affinity to IGF binding proteins nor proteinase inhibitors obliterated the IGF-1 resistance. In CRF rats, skeletal muscle IGF-1R mRNA was increased; displacement ligand binding studies and affinity labeling of the IGF-1R alpha subunit indicated increased total skeletal muscle IGF-1R number with normal affinity. However, both autophosphorylation of the IGF-1R beta subunit (i.e., IGF-1R tyrosine kinase) and the IGF-1R tyrosine kinase activity towards exogenous insulin receptor substrate-1, a natural substrate for IGF-1R tyrosine kinase, were reduced in CRF fats. These data indicate that in skeletal muscle of CRF rats there is resistance to the IGF-1 effects on protein synthesis and degradation and decreased IGF-1 and IGF-1 mRNA levels; IGF-1R mRNA and number are increased; but activity of IGF-1R tyrosine kinase is impaired. This postreceptor defect may be a cause of the skeletal muscle resistance to IGF-1 in CRF.

Antimutagenic effects of taurine in a bacterial assay system.

Taurine (2-aminoethanesulfonic acid) was evaluated as an antimutagen in the Ames Salmonella tester strain assay. Taurine inhibited mutagenesis by doxorubicin (-74%), bleomycin (-55%), mitomycin C (-56%), and 2-aminofluorene (-52%), but not danthrone or benzo(a)pyrene, in strain TA102. In strain TA98, doxorubicin mutagenicity, but not that of 2-aminofluorene or benzo(a)pyrene, was inhibited by taurine. N-Methyl-N'-nitro-N-nitrosoguanidine (-73%), but not dexon, mutagenicity was inhibited by taurine in strain TA100. Taurine inhibited those mutagens against which it was effective in a dose-related fashion. Taurine was more effective in inhibiting doxorubicin mutagenicity in strain TA102 than its analogues hypotaurine, beta-alanine, and guanidinoethanesulfonic acid or alanine or glycine. The observed inhibition may indicate a role for taurine in modulating the activity of oxidant species.

A low lymphocyte percentage is a predictor of mortality and hospitalization in hemodialysis patients.

OBJECTIVES: Lymphocyte percentage (LYM%), an independently measured value to reflect peripheral lymphocyte count and a possible nutritional marker, may be related to clinical outcome in maintenance dialysis (MHD) patients. STUDY DESIGN AND SETTING: We examined the associations of the baseline white blood cell count (WBC) and LYM% with 12-month mortality and three measures of hospitalization in a cohort of 1,283 MHD patients from 10 outpatient DaVita dialysis clinics in Los Angeles County, as well as in a subcohort of 372 MHD patients with additional measures of inflammation, nutrition and comorbidity. Multi-variate Cox and Poisson models that included 13 co-variates including case-mix features, dialysis dose, blood hemoglobin and serum albumin were explored. RESULTS: Patients, aged 57.8 +/- 15.2 years, included 49% men and 49% diabetics. Baseline WBC was 7,353 +/- 2.427 per microl, and LYM% was 21.2 +/- 7.3%. LYM% had significant correlations with "malnutrition-inflammation score" and inverse correlations with serum interleukin-6. The WBC and LYM% had significant but opposite predicting values for mortality and hospitalization, indicating that a high WBC and a low LYM% were each independently associated with increased mortality. After dividing each variable into four quartiles, only the highest WBC quartile (> or = 8,500) but not the other middle two quartiles, predicted increased mortality. However, all three lower quartiles of LYM% vs. the highest quartile (based on quartile cutoffs of 16%, 20.3% and 25.5%) were significantly and progressively associated with greater risks of mortality and hospitalizations. The absolute lymphocyte count (LYM% times WBC/100) exhibited somewhat similar trends but its outcome predictability was not as strong as LYM%. CONCLUSIONS: A high WBC and a low LYM% are associated with significant increase in mortality and hospitalization in MHD patients. Lymphocyte percentage, compared to absolute lymphocyte count, appears to be a better nutritional and anti-inflammatory marker and a more sensitive predictor of mortality and hospitalization in MHD patients.

Role of the splanchnic tissues in the pathogenesis of altered carbohydrate metabolism in patients with chronic renal failure.

To evaluate the contribution of the splanchnic area to the carbohydrate abnormalities associated with chronic uremia, the splanchnic exchange of glucose and gluconeogenic substrates was quantitated basally and after an iv glucose load in nine uremic patients with impaired glucose tolerance and seven control subjects. In the basal state, blood glucose and splanchnic glucose production were similar in the two groups. During glucose infusion (33 mumol/kg.min for 90 min), blood glucose reached significantly higher levels in the uremic patients than in controls (P less than 0.02). Plasma insulin increased slightly more in uremic patients than in controls (P less than 0.05 at 15 min). Both basal and postglucose glucagon levels were 2- to 3-fold higher in uremic patients than in normal subjects (P less than 0.05-0.02). In both groups, splanchnic glucose balance switched from net output in the basal state (-9.4 +/- 0.5 and -8.0 +/- 1.1 mumol/kg.min in normals and uremics, respectively) to net uptake with glucose infusion. However, this response was less marked in the uremic patients than in normal subjects (P less than 0.05-0.02 at 30 and 90 min). The cumulative net splanchnic glucose balance over the 90-min study period was 538 +/- 55 mumol/kg in normal subjects and 279 +/- 89 in uremic subjects (P less than 0.05). A net splanchnic lactate uptake was present in the basal state in normal (4.2 +/- 0.5 mumol/kg.min) and uremic subjects (3.4 +/- 0.5). During glucose infusion, in normal subjects splanchnic lactate exchange switched to a net output (-4.0 +/- 1.6 mumol/kg.min), whereas in the uremic group it remained as a net uptake (1.1 +/- 0.7) throughout the study period. Splanchnic gluconeogenic amino acid uptake was similar in the two groups in the basal state (1.8 +/- 0.1 mumol/kg.min and 2.2 +/- 0.2 in normal and uremic subjects, respectively). Glucose infusion caused a marked fall in amino acid uptake by liver in normal subjects, whereas no change was observed in the uremic group (0.9 +/- 0.3 and 1.9 +/- 0.2 mumol/kg.min, respectively). Splanchnic glycerol uptake was not different in the two groups in the basal state (0.75 +/- 0.2 and 1.1 +/- 0.2 mumol/kg.min) and decreased to a similar extent during glucose infusion. We conclude the following. 1) In uremic patients with glucose intolerance but normal fasting glycemia, the splanchnic metabolism of glucose and gluconeogenic substrates is normal in the postabsorptive state.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical and metabolic responses to parenteral nutrition in acute renal failure. A controlled double-blind study.

1. Thirty patients with acute renal failure who were unable to eat adequately were evaluated while they received parenteral nutrition with glucose alone (n = 7), glucose and 21 g/day essential amino acids (EAA, n = 11) or glucose, 21 g/day essential and 21 g/day nonessential amino acids (ENAA, n = 12). Energy intake did not differ with the three treatments. Patients were studied in a prospective double blind fashion. 2. Thirteen patients recovered renal function and 11 survived to leave the hospital. Those in whom renal failure was attributed to hypotension and/or sepsis had a poorer recovery of renal function (17%) and survival (17%). Recovery of renal function and survival was greater in patients on the medical service as compared to the surgical service and in those who received more energy. Recovery of renal function was worse in those treated with dialysis. There were no differences in recovery of renal function of survival among the three treatment groups. 3. Many patients were markedly catabolic as indicated by nitrogen balances, urea in nitrogen appearance rates (UNA), serum protein concentrations, and plasma amino acid levels. There was no correlation between the degree of catabolism and recovery of renal function or survival. Mean UNA in individual patients also correlated with body weight. Among the three groups, however, UNA was significantly less with the group receiving EAA as compared to ENAA. 4. Serum protein concentrations were lower than normal in all treatment groups. Serum albumin fell significantly during the treatment in the more catabolic patients. Plasma amino acid levels tended to fall in all three groups and concentrations at the end of the treatment were frequently lower than normal. 5. These data suggest that acute renal failure patients who are unable to eat adequately are often hypercatabolic and have a high mortality, particularly if hypotension or sepsis is the cause of renal failure. The improved survival in those with higher energy intakes, the high rate of net protein breakdown, the low serum protein levels and the reduced plasma concentrations of both essential and nonessential amino acids suggest that greater quantities of energy and both essential and nonessential amino acids may be beneficial to such patients.

McCollum Award Lecture, 1996: protein-energy malnutrition in maintenance dialysis patients.

There is a high prevalence of protein-energy malnutrition in patients with chronic renal failure who are undergoing maintenance dialysis therapy. The high prevalence of malnutrition is a potentially serious problem because indexes of protein-energy malnutrition are powerful predictors of mortality in maintenance dialysis patients. Although the data do not prove that improving nutritional intake will reduce mortality, nonrandomized studies suggest that provision of addition amino acids and energy to such patients is associated with reduced mortality. There are many causes for protein-energy malnutrition in maintenance dialysis patients. Among the three most important factors are the nutritional status of the patient before commencing dialysis therapy, inadequate protein and energy intakes after they become dialysis patients, and acute and chronic illnesses. Improving the nutrient intake of maintenance dialysis patients is a challenging task because most chronic renal failure patients with malnutrition are anorectic, and dietary counseling has had limited success at increasing their nutrient intake. Other methods for improving nutritional status in adults, infants, and children with chronic renal failure that have been tried with varying degrees of success include increasing the dose of dialysis and the use of food supplements and tube feeding. Less well-proven techniques for the treatment of protein-energy malnutrition include intradialytic parenteral nutrition. The use of appetite stimulants and such growth factors as rhGH and rhIGF-I are still in the experimental stage.

Newer concepts of the indispensable amino acids.

In healthy adult humans, eight amino acids (isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine) were shown classically by nitrogen balance studies to be indispensable. Subsequent studies classifying histidine as indispensable are reviewed in this article. We also review the evidence that in certain nutritional or disease states or in certain stages of development otherwise dispensable amino acids may become indispensable. Arginine, citrulline, ornithine, cysteine, and tyrosine thus may be considered as acquired indispensable amino acids. Evidence for the indispensability of taurine is also considered. We propose a classification of the indispensability of amino acids based on clinical and therapeutic considerations.

Effects of amino acid infusion and renal failure on the uptake and release of amino acids by the dog kidney.

Net production and utilization (Qmet) of amino acids and ammonia were assessed in the left kidney of 11 normal and eight chronically uremic female dogs. Studies were conducted at the end of two 120-min infusions, first with half-normal saline and then with amino acids which increased plasma concentrations to postprandial levels. In the normal dogs, Qmet for a number of amino acids and ammonia was significantly positive (i.e., net production) or negative (i.e., net utilization). Qmet became more negative with the amino acid infusion. In the uremic dogs, Qmet for amino acids and ammonia was qualitatively similar to normal and tended to change in the same direction with the amino acid infusion. Although the absolute values for Qmet were usually less in the uremic dogs, with the amino acid infusion their mean fractional Qmet (Qmet/creatinine clearance) was often greater. A substantial proportion of the infused amino acids was removed by the kidney) in both groups of dogs. In the uremic dogs, there was evidence for preservation of glomerular-tubular balance between the filtered load of amino acids and tubular reabsorption. Data also suggest that the kidney may release sufficient quantities of certain amino acids into renal venous blood (e.g., serine) to affect the plasma levels. These findings indicate that the dog kidney may make an important contribution to total synthesis or metabolism of certain amino acids by the body and may also affect plasma concentrations of some amino acids. During amino acid infusion, the kidney plays a major role in removal of the added amino acids. In renal failure these functions are decreased, but compared to the fall in glomerular filtration rate, they are relatively well preerved.

Valine metabolism in normal and chronically uremic man.

Valine metabolism was investigated in five normal and three nondialyzed chronically uremic subjects eating 40 +/- SEM 1 and 53 (range 40 to 80) protein diets respectively, in a metabolic research unit. Subjects were injected iv with a tracer dose of L-valine-1-14C while they fasted, and specific activity of plasma valine-14C and expiration of 14CO2 were monitored for two hours. Plasma valine was significantly lower in the uremic patients than in the normal subjects (P less than 0.05). In the uremic patients, specific activity of plasma valine fell less rapidly and remained higher, and expiration of 14CO2 was not different from normal subjects. A two-pool model for valine metabolism was derived which indicated that in uremic patients there was a significant decrease in both valine pools and in the rate of irreversible loss, i.e., valine incorporated into larger molecules, degraded, or excreted. Valine degradation was estimated to be decreased in the uremic patients.

Vitamin B-6 deficiency and renal function and structure in chronically uremic rats.

In preliminary studies, rats with chronic renal failure (CRF) demonstrated worsening renal function, as measured by urea clearance, when fed vitamin B-6-deficient diets. However, urea clearance is not a precise measure of glomerular filtration rate (GFR) and these studies did not indicate the mechanism for the reduced GFR. To measure renal function more precisely and to assess whether B-6 deficiency augments renal injury, we examined [14C]inulin clearance, urine oxalate excretion, and renal histopathology in rats with CRF pair fed to receive a pyridoxine-replete or -deficient diet for 3 or 6 wk. After 3 or 6 wk, pyridoxine-deficient rats had significantly lower [14C]inulin clearances and increased urine oxalate excretion. Histological evaluation indicated increased renal damage in kidneys from pyridoxine-deficient rats as compared with tissue from pyridoxine-replete rats. These findings suggest that in rats with CRF, vitamin B-6 deficiency reduces the GFR and increases renal scarring.

Altered plasma free and protein-bound sulfur amino acid levels in patients undergoing maintenance hemodialysis.

The plasma sulfur amino acid status of maintenance hemodialysis (MHD) patients has not previously been comprehensively investigated. We measured plasma sulfur amino acid levels in 24 MHD patients (12 fasted, 12 nonfasted) both before and after a routine 4-h hemodialysis and in 13 normal individuals (seven fasted, six nonfasted). Plasma free cystine, homocystine, cysteine-homocysteine-mixed disulfide (MDS), methionine, and taurine and protein-bound cysteine and homocysteine were measured. In nonfasted patients, plasma homocystine and MDS were not measured. Fasted patients predialysis had elevated plasma free cystine, homocystine, MDS, methionine, and taurine; all of these, except taurine, fell during dialysis. In nonfasted patients, plasma free cystine was elevated. Protein-bound cysteine and homocysteine were elevated predialysis and postdialysis in all patients; protein-bound cysteine fell during dialysis but remained above normal. In MHD patients predialysis, plasma free cystine levels correlated with plasma MDS, protein-bound cysteine, and age. These findings indicate pervasive alterations in plasma sulfur amino acid levels in MHD patients.

Nutritional and metabolic response to catabolic stress in uremia.

Metabolic balance studies were conducted in five nondialyzed chronically uremic patients and four patients undergoing maintenance hemodialysis or peritoneal dialysis who had sustained an acute intercurrent illness. Nitrogen balance became negative in all patients. In eight patients who did not have marked fluid removal, serum total protein, albumin and transferrin fell significantly. Negative nitrogen balance was caused by three factors: 1) decreased nitrogen intake, which wasn't always readily apparent 2) increased urea nitrogen appearance, and 3) in peritoneal dialysis patients with peritonitis, protein losses into dialysate. In the chronically uremic patients, urea nitrogen appearance correlated closely with total nitrogen output and appears to be a good predictor of total nitrogen losses.

Effect of food intake and fasting on gastrointestinal lead absorption in humans.

The effect of food intake versus brief fasting on gastrointestinal absorption of lead was measured in five healthy men who were living in a metabolic unit and eating constant lead diets. Lead absorpiton was assessed by the difference between dietary intake and output of 1) lead tracers composed of nonradioactive isotopes which were ingested as a single dose either with food or during a 16-hr fast, 2) lead tracers ingested with meals for relatively long periods (2 to 124 days), and 3) total led in ingested foods. Absorption estimated by 1) was confirmed by increments in tracer concentrations in blood. Lead tracers were given as nitrate, cysteine complex, or sulfide. Absorption was 10.3 +/- 2.2% (SD) for food lead; 8.2 +/- 2.8% for tracers ingested with food; and 35 +/- 13% (P < 0.01) percent for tracers ingested without food. The increased absorption of lead when ingested without food should be considered when the hazards of exposure to lead are determined.