Radioimmunoassay measurement of albumin in urine is a valid method for monitoring analbuminemia in rats.

Plasma and urinary albumin levels, urinary creatinine and urine volumes were measured at two-week intervals in Nagase analbuminemic rats (NAR) of either sex at ages from 42 to 154 days. Age matched Sprague Dawley (SD) rats were used as controls. Plasma concentrations of immunoreactive albumin (iALB) in NAR ranged from 0.007 +/- 0.002 to 0.023 +/- 0.003 mg/ml, and were lower in younger rats. In SD rats, plasma iALB concentrations ranged from 18.9 +/- 1.0 to 46.2 +/- 6.4 mg/ml. Urinary iALB output in NAR was less than 0.05 micrograms/mg creatinine measured over a 24 hr period, whereas it was greater than 20 micrograms/mg creatinine in the SD rats. Measurement of urine iALB concentrations in the NAR colony appears to be a reliable and a non-invasive method for monitoring the persistence of hypoalbuminemia.     

Detection of ornithine transcarbamylase deficiency heterozygotes by measuring of urinary uracil

The importance of detecting heterozygosity for X-linked ornithine transcarbamylase deficiency is well known. Although the DNA analysis and the allopurinol loading tests are commonly used for this purpose, both methods require complicated procedures. In order to establish a simple test for detecting female heterozygotes, we examined the uracil and orotic acid in single-voided urine samples from 70 healthy women, and from 12 asymptomatic females with ornithine transcarbamylase deficiency. Based on the results of healthy women, we were able to determine a screening cut-off line of 11.9 micromol/mmol creatinine (mean +/- 1SD in logarithmic form) for uracil. Using this cut-off line, the sensitivity of OCT heterozygotes was 100%. We were also able to establish a second cut-off line of 28.9 micromol/mmol creatinine (mean +/- 3SD in logarithmic form) for diagnosis. Using this second cut-off line, the specificity of OCT heterozygotes was 100%. Our study has shown that the measurement of urinary uracil is a relatively simple and effective method for detecting female heterozygotes.     

Determination of urinary orotic acid and uracil by capillary zone electrophoresis

We describe a simple method for measuring orotic acid and uracil concentration in urine by capillary zone electrophoresis in 20 mM Na-borate buffer, pH 9.2. The method was applied for studying a patient with HHH (hyperomithinemia, hyperammonemia and homocitrullinuria) syndrome. A high value of uracil excretion was found during periods of relatively low orotic acid excretion and normal ammonemia. The orotic acid level in urine was increased by increasing protein intake.     

Orotic acid, a new promoter for experimental liver carcinogenesis

Male Fischer 344 rats initiated with 1,2-dimethylhydrazine 2HCl (100 mg/kg) given 18 hr after partial hepatectomy and exposed to a diet containing 1% orotic acid for 13 months developed a 100% incidence of hepatocellular carcinoma. The creation of nucleotide pool imbalances by dietary orotic acid, for e.g., an increase in uridine nucleotides and a decrease in adenine nucleotides, was considered as a possible mechanism for the promotional effect of orotic acid on liver carcinogenesis. The significance of this hypothesis is that altered nucleotide pools affect both genomic as well as membrane organization. Consistent with this hypothesis is our finding that feeding rats with a diet containing 1% orotic acid for 10 weeks resulted in a liver DNA damage as monitored by its slower sedimentation in alkaline sucrose gradients compared to the corresponding controls. To assess the general applicability of this hypothesis, nucleotide pool imbalances were created by using methods other than feeding orotic acid and their effect on the incidence of gamma-glutamyltransferase positive foci in carcinogen initiated rats was determined. The results obtained indicated that rats initiated with 1,2-dimethylhydrazine.2HCl (100 mg/kg) given 18 hr after partial hepatectomy and exposed to diet deficient in arginine, a regimen that causes an increased synthesis and excretion of orotic acid, or were fed diets containing 1% thymidine or 1% thymine developed greater number of gamma-glutamyltransferase positive foci compared to the corresponding controls fed the basal diets. These results were interpreted to indicate that orotic acid exerts its promotional effect probably by creating an imbalance in nucleotide pools. One of the mechanisms by which an imbalance of nucleotide pools influences the pathogenesis of the carcinogenic process may be by inducing perturbations in the DNA.     

A rapid technique for detection of resistance to chloramphenicol in Streptococcus pneumoniae and comparison with minimum inhibitory concentration and disk-diffusion methods

Fifty-two strains of Streptococcus pneumoniae were examined for production of chloramphenicol acetyltransferase (CAT) by a rapid technique based upon induction of enzyme activity and chemical assay. This method was compared with one measuring the minimum inhibitory concentration (MIC) by agar dilution and a diffusion test with disks containing 10 micrograms, 30 micrograms and 50 micrograms of chloramphenicol. The MIC for 13 chloramphenicol-resistant strains was 16 mg/L and for 39 sensitive strains less than or equal to 4 mg/L. The chemical assay clearly distinguished resistant from sensitive strains; it was technically simple and provided results within 90 min. The distinction between sensitive and resistant bacteria in the disk diffusion assay was clearer with 10-micrograms than with 30-microgram and 50-micrograms disks. However, the chemical CAT assay, with enzyme induction, is recommended when a rapid result is required.     

Maternal behavior is related to prepartum urinary estradiol levels in red-bellied tamarin monkeys

This is the first study in a primate, the red-bellied tamarin (Saguinus labiatus), to demonstrate a correlation between urinary estradiol during late pregnancy and postpartum infant-directed behavior. Females were defined as good (N = 6) or poor (N = 6) mothers, and were selected so that both groups contained 3 females with and 3 without prepubertal experience with infants. Females with prepubertal experience of infants were defined as good or poor mothers if 2 or less than 2 infants survived one week, respectively; females without such experience were defined as good or poor mothers if at least 1, or 0 infants survived one week, respectively. Five of the six good mothers had 2 surviving infants; 10 of the 13 infants of poor mothers died at day 0. Prepartum urinary total estradiol concentrations were constant in good mothers (5-4 weeks prepartum: 32.29 +/- 3.65 micrograms/mg creatinine; 1 week prepartum: 33.76 +/- 5.02 micrograms/mg CR.; p greater than 0.98), but declined significantly in poor mothers (5-4 weeks prepartum: 38.34 +/- 7.07 micrograms/mg Cr.; 1 week prepartum: 18.35 +/- 4.72 micrograms/mg Cr.; p less than 0.0004). At 1 week prepartum, estradiol was significantly higher in good mothers (p less than 0.03). When analysed separately, only good and poor mothers without prepubertal experience of infants had significantly different urinary estradiol concentrations. In the 2-hour postpartum period, good mothers spent more time lick-cleaning (p less than 0.02), carrying and nursing infants; poor mothers rubbed off clinging infants more, their infants spent less time being carried (p less than 0.03), and apparently starved because they had no opportunity to suckle.     

Dietary and metabolic manipulations of the carcinogenic process: role of nucleotide pool imbalances in carcinogenesis

Perturbations in DNA and/or membranes are considered to be important for the carcinogenic process. A search for nutritional and metabolic means of disturbing the homeostasis of DNA and membranes revealed that nucleotide pools offer an exciting possibility. An imbalance in nucleotide pools can exert a two-pronged attack on both DNA and membranes. When given to rats, orotic acid, a precursor of pyrimidine nucleotides, results in an imbalance in nucleotide pools (an increase in uridine nucleotides and a decrease in inosine/adenine nucleotides), alterations in both DNA and membranes, and promotion of carcinogenesis in the liver initiated by chemical carcinogens. Agents such as adenine and allopurinol, which inhibit the metabolism of orotic acid and thereby decrease the formation of uridine nucleotides, and galactosamine, which traps uridine nucleotides, inhibited the promotional effects of orotic acid in the liver. These results suggested that orotic acid needs to be metabolized to uridine nucleotides and the creation of a subsequent imbalance in nucleotide pools is important for the promotional effects of orotic acid. To determine whether the creation of a nucleotide pool imbalance is a more general mechanism of tumor promotion, two lines of approach were investigated. One was to determine the effect of orotic acid on promotion of carcinogenesis in other organs, and the second approach was to determine how to induce nucleotide pool imbalances by means other than orotic acid administration. It is interesting to note that orotic acid promotes carcinogenesis in duodenum initiated by azoxymethane. Regarding the second approach, it became apparent that several metabolic disturbances result in increased orotic acid synthesis and alterations in nucleotide pools.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determination of the histamine metabolite tele-methylimidazoleacetic acid and of creatinine in urine by the same HPLC system

OBJECTIVE AND DESIGN: To develop an HPLC method with UV detection for determination of tele-methylimidazoleacetic acid (t-MelmAA) in urine of man or animals, which is reliable, simple and less expensive than existing GC/MS techniques. METHOD: The elaborated procedure enables separation of t-MelmAA from its pros-isomer (p-MelmAA) as well as from imidazoleacetic acid. As an internal standard tele-ethylimidazoleacetic acid (t-EtlmAA) is used. The acids, after being converted to their stable isopropylesters, are extracted at pH 6.0-6.5. The further separation prior to HPLC utilises a small cellulose phosphate column. The HPLC system is isocratic with a C18 column and mobile phase consisting of an aqueous solution of SDS at pH 3.5 mixed with acetonitrile (65:35). An advantage of this system is that it can be used to determine the urine creatinine concentration to express excreted t-MelmAA in mmol/mol creatinine. RESULTS AND CONCLUSIONS: The method applicability is demonstrated in repeated studies in mastocytosis patients. The broad range of excretion values, from normal up to a high level (0.9 to 30 mmol/mol creatinine), indicates that it can be satisfactorily used for evaluation of histamine turnover under various clinical conditions. The method appears to be a good alternative to GC/MS based ones.     

Enzyme-linked immunosorbent assay determination of specific rubella antibody levels in micrograms of immunoglobulin G per milliliter of serum in clinical samples.

A "microgram assay" is described in which solid-phase enzyme-linked immunosorbent assay is used for the determination of specific rubella immunoglobulin G (IgG) antibody levels in micrograms per milliliter of serum. The quantitation was based on a standard curve obtained by using a reference serum, for which the specific IgG content was assayed by immunochemical purification. IgG was first purified and specific rubella antibodies were separated by an immunoadsorbent prepared by linking rubella virus antigens to Sepharose 4B. By using IgG-specific conjugate, the levels of specific rubella IgG antibodies could then be determined from clinical samples. Seronegative samples showed antibody levels less than 1 microgram/ml, whereas levels up to several hundred micrograms per milliliter were detected in some postinfection sera. The correlation between microgram antibody levels and hemagglutination inhibition titers was linear. The method offers a simple and sensitive antibody assay which could be used both for the laboratory diagnosis of acute rubella and for the evaluation of immunity.     

Sialic acid levels and lag time of growth in chemically defined medium containing 200 mM phosphate among strains of various serotypes of Streptococcus agalactiae

The type-specific capsular polysaccharide antigen of Streptococcus agalactiae has in previous experimental studies been considered a significant antiphagocytic factor, whereas the lipoteichoic acid moiety has been suggested to be a factor in adherence to human fetal cell lines. Since epidemiological data concerning these cell constituents in strains from the genital tract are lacking, we attempted serotyping and analysis of these constituents of 100 vaginal isolates. The capsular polysaccharide level was shown to be the amount of sialic acid that occupied the terminal side chains of the polysaccharide. We carried out a study to ascertain whether strains exhibited a lag time of growth in a chemically defined medium containing 200 mM phosphate, which has been suggested to be characteristic of strains with high lipoteichoic acid levels. Strains were classified, on the basis of the results of distribution of sialic acid levels, into three categories: (i) strains with a low sialic acid content of equal to or less than 9 micrograms/mg of cell dry weight; (ii) strains with a moderate sialic acid content of more than 9 but less than 12 micrograms/mg of cell dry weight; and (iii) strains with a high sialic acid content of equal to or more than 12 micrograms/mg of cell dry weight. Strains that belonged to the last category, which, as previous experimental data indicate, are potentially virulent strains, were significantly distributed among isolates of types Ia (P less than 0.001) and III (P less than 0.05). On the other hand, strains exhibiting a lag time of growth in the above-mentioned medium were detected to a significant extent in type III isolates (P <0.02). These results may be related to the epidemiological finding that isolates from neonates with late-onset infection were more frequently serotype Ia and III isolates.     

Rapid analysis of nickel in urine by electrothermal atomic absorption spectrophotometry

A method is described for analysis of nickel in urine, which involves dilution of urine with dilute nitric acid and direct quantitation of nickel by electrothermal atomic absorption spectrophotometry with Zeeman background correction. The detection limit for nickel is 0.5 micrograms per L of urine; the coefficient of variation of replicate determinations is 4 to 5 percent (within-run) and 6 percent (run-to-run). Recovery of nickel added to urine (20 micrograms per L) averages 99 +/- 5 percent (mean +/- SD). Analytical results agree closely with measurements by the International Union of Pure and Applied Chemistry (IUPAC) reference procedure (correlation coefficient = 0.99). Nickel concentrations in urine specimens from 34 non-exposed, healthy, adult persons living in Connecticut average 2.0 +/- 1.5 microgram per L (range = 0.5 to 6.0 micrograms per L). Urine nickel concentrations are directly correlated with urine creatinine concentrations and specific gravity measurements. Elevated concentrations of nickel are observed in urine specimens from nickel-exposed workers, including nickel electroplating workers (mean = 27 micrograms per L, range = 3.1 to 82 micrograms per L, N = 19) and nickel battery workers (mean = 32 micrograms per L, range = 2.8 to 103 micrograms per L, N = 7). This method is more rapid and convenient than previous techniques and is suitable for routine use in clinical and industrial laboratories.     

Screening of type Ia and Ib Streptococcus agalactiae strains with high sialic acid levels by determination of susceptibility to tetracyclines

The type-specific capsular polysaccharide antigen of Streptococcus agalactiae is recognized to be an antiphagocytic factor in strains having large amounts of it. In the present study, it was indicated that vaginal isolates of types Ia and Ib could be classified into two groups on the basis of both their levels of the sialic acid, which occupies the terminal side chains of the polysaccharide, and their susceptibility to tetracyclines: one group comprised strains with low sialic acid levels (less than 9 micrograms/mg of cell dry weight) as well as with susceptibility to tetracyclines (MIC, less than or equal to 0.5 micrograms/ml), and the other comprised strains with higher sialic acid levels (greater than or equal to 9 micrograms/mg) and resistance to tetracyclines (MIC, greater than or equal to 8 micrograms/ml). A few isolates were found to have low levels of sialic acid and to be resistant to tetracyclines, but no isolates that were both relatively high in sialic acid and susceptible to tetracyclines were ever detected. Among strains of those serotypes, the MICs of tetracyclines were not in proportion to the sialic acid levels and were not affected when the sialic acid levels of each strain were altered by using Todd-Hewitt broth with various concentrations of Na2HPO4 and glucose. It was, therefore, apparent that the correlation of sialic acid levels with susceptibility to tetracyclines was not related directly to the sialic acid content or to the amount of the capsular polysaccharide. Since no plasmid DNAs were detected among representative strains that were tetracycline resistant, it was apparent that at least for the strains tested, resistance was chromosomal gene associated. In strains of S. agalactiae of types of Ia and Ib, the determination of susceptibility to tetracyclines was considered to be useful for screening strains with higher sialic acid levels.     

Assay of clomipramine and its demethylated derivative by liquid chromatography

Clomipramine and desmethylclomipramide are determined on 1 ml of human blood plasma, after extraction with hexane and high-performance liquid chromatography using a cyanopropyl silane column and UV detection at 280 nm. Imipramine and desipramine are used as internal standards. The methods allow detection limits of 5 micrograms/l; 15.9 nmol/l (clomipramine) to 10 micrograms/l; 33.2 nmol/l (desmethylclomipramine). The precision of the method at clomipramine concentrations of 0.05 to 0.2 mg/l was indicated by a coefficient of variations less than 6% for clomipramine and less than 7% for desmethylclomipramine.     

Liquid chromatography-electrospray tandem mass spectrometry of acidic monoamine metabolites

A new method based on liquid chromatography-tandem mass spectrometry has been developed for the determination of monoamine metabolites, i.e., homovanillic acid (HVA), vanilmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in human urine. Analytes were separated on a C16 amide (5 cm, 5 microm) column and ionized by negative ion electrospray. Operating in the selected-reaction monitoring mode, linearity was established over three-orders of magnitude and limits of detection were in the range 30-70 microg/l. Precision calculated as RSD was within 0.8-5.2% for all intra- and inter-day determinations. The method was applied to the quantitative analysis of monoamine metabolites in 700 urine samples from occupationally (adults) and environmentally (both children and adults) exposed people living in areas with different soil contamination from lead. The urinary excretion of monoamine metabolites was significantly higher (P<0.001) in the subgroup of children living in polluted areas as compared to the control group (HVA, 6.03 vs. 4.57 mg/g creatinine; VMA, 5.33 vs. 4.37 mg/g creatinine; 5-HIAA 3.24 vs. 2.45 mg/g creatinine). In adults belonging to both groups of subjects occupationally and environmentally exposed, no differences were detected in the urinary concentration of monoamine metabolites. However, adults showed lower values of HVA (2.57 mg/g creatinine), VMA (2.17 mg/g creatinine) and 5-HIAA (2.09 mg/g creatinine) as compared to children groups.     

In vitro activity of the combination ticarcillin-clavulanic acid on bacterial isolates in surgery

The in vitro activity of ticarcillin in combination with clavulanic acid was tested, by disc diffusion, against 1,380 clinical bacterial isolates and was compared with that of ticarcillin alone. 83.8% of the isolates were susceptible to ticarcillin + clavulanic acid, whereas 56.6% were susceptible to ticarcillin alone. Minimal inhibitory concentrations (MIC) of ticarcillin in the presence of 4 micrograms/ml of clavulanic acid were determined against 157 ticarcillin resistant (MIC greater than 128 micrograms/ml) but ticarcillin + clavulanic acid susceptible strains of Gram negative bacilli and against 20 strains of beta-lactamase producing Staphylococcus aureus. With the addition of clavulanic acid, MICs of ticarcillin were respectively less than or equal to 16 micrograms/ml and less than or equal to 64 micrograms/ml for 50 and 90% of the Gram negative bacilli. All the Staphylococcus aureus were inhibited by concentrations of ticarcillin less than or equal to 1 microgram/ml.     

Comparison of 100 micrograms TRH intravenously and 40 mg TRH orally in euthyroidism (author's transl)

Euthyroid in-patients were investigated with 100 micrograms TRH given intravenously and with 40 mg TRH given orally in order to compare the sensitivity of intravenous and oral TRH-test. In all patients (age 15-91 years) maximal TSH-levels 180 min after 40 mg TRH are significantly (p less than 0.01) higher than maximal TSH-levels 30 min after 100 micrograms TRH. In patients under 50 years of age TSH-30 and TSH-180 are identical on average (6.42 +/- 0.29 microunits/ml vs. 6.53 +/- 0.54 microunits/ml/log x +/- SDlog). In patients older than 50 years TSH-30 is significantly lower (p less than 0.02) than in patients aging less than 50 years (2.11 +/- 0.88 microunits/ml vs. 6.42 +/- 0.29 microunits/ml). Both age-related groups demonstrate no significant difference (p greater than 0.2) in TSH-180 after 40 mg TRH (6.53 +/- 0.54 microunits/ml vs. 3.65 +/- 0.74 microunits/ml). 14 cases (34%) are low or non responders to 100 micrograms TRH intravenously, 8 (19.5%) only following 40 mg TRH orally. Patients with complete TSH-suppression (both iv. and oral TRH-test negative) show significant (p less than 0.05) higher ETR, T4 and fT4 than patients with partial TSH-suppression (iv. negative and oral TRH-test positive). The dose of 100 micrograms TRH does not increase the sensitivity of the test, the specificity is decreased in older patients, the dose of 100 micrograms TRH seems to be to low to yield reliable results. 40 mg TRH orally does not show any false positive findings, because TSH-stimulation is longer and more intensive. T3 increase three hours after orally TRH-application indicates an intact feedback mechanism.     

Laboratory detection of ciprofloxacin resistant Neisseria gonorrhoeae.

During 1989 and 1990 strains of Neisseria gonorrhoeae with reduced susceptibility to ciprofloxacin were isolated in laboratories across the United Kingdom. Treatment failures were associated with some of these infections. These strains were detected by quantitative susceptibility testing because the zone of inhibition around 5 micrograms ciprofloxacin discs shows little decrease in size even with those that are the most resistant. This study determined that strains with reduced susceptibility to ciprofloxacin (MIC of greater than or equal to 0.05 mg/l) produced no zone of inhibition around a commercially available disc containing 30 micrograms of nalidixic acid. Ciprofloxacin sensitive (MIC of less than 0.05 mg/l) strains, however, grew with a large zone (greater than 21 mm) around this disc. These observations suggest that laboratories could adopt this disc test to detect those strains for which ciprofloxacin is not appropriate treatment.     

Immunological safety assessments of anti-IgE antibody which is detached from therapeutic immunoadsorbents for removing IgE

Assessments were made of the safety of antibodies which might be detached from a therapeutic immunoadsorbent (IA) during extracorporeal circulation, with respect to possible immunological responses to such antibodies. The IA used was antihuman IgE antibody (a-IgE Ab) immobilized on a carrier, for removal of IgE from patients' plasma. The antibody was raised in goats and isolated to give an IgG fraction. This fraction was either used without further purification or was subjected to immunoaffinity purification. The active anaphylaxis test in guinea pigs indicated that positive responses were not observed at doses of less than 0.1 micrograms of goat IgG per animal. Rabbits given goat IgG intravenously 3 times a week for 8 weeks did not produce the specific antibody against goat IgG at doses of less than 0.05 micrograms/kg, which corresponds to less than 3 micrograms for an adult with a body weight of 60 kg. However, none of the rabbits given goat IgG at 2.5 mg/kg showed any toxic reactions and different patterns of the body weight growth from these in the control group. In addition, we tested whether immunoaffinity purified a-IgE Ab could trigger Type I hypersensitivity in a monkey model. Anaphylactic reactions were not observed after a single intravenous injection of a-IgE Ab at less than 10 micrograms/kg. These in vivo results are useful to judge whether the amount of antibody that leaks from a therapeutic IA is acceptable or not in a clinical situation.     

Urinary hyaluronic acid elevation in Hutchinson-Gilford progeria syndrome

The basic genetic defect in the Hutchinson-Gilford Progeria Syndrome (progeria), a premature aging syndrome, is unknown. To investigate possible defects in hyaluronic acid (HA) metabolism in this disease, the urinary excretion of HA was studied. Urine specimens from 11 patients with this disorder were examined for HA by a novel high performance liquid chromatography (HPLC) technique. In patients with progeria, HA excretion ranged from 169 micrograms HA/g creatinine to 1440 micrograms HA/g creatinine. In normal age-matched controls, HA excreted ranged from 0 to 77 micrograms HA/g creatinine. In all, a mean 17-fold increase in HA excretion was observed in patients with progeria when compared with age-matched normal controls. Total glycosaminoglycan (GAG) excretion was not elevated. Amongst normal controls, a modest age-related increase in HA excretion was observed. These results suggest that urinary HA levels are abnormally elevated in progeria.     

Aluminum-citrate interaction in end-stage renal disease.

The influence of a sodium citrate/citric acid mixture on the gastrointestinal (GI) absorption of aluminum (Al) from an Al(OH)3 preparation was evaluated in six stable maintenance hemodialysis patients. Plasma Al concentrations were determined serially after each of the following treatment sequences (I) Al(OH)3; (II) Al(OH)3 + sodium citrate/citric acid; (III) sodium citrate/citric acid; (IV) Al(OH)3 + NaHCO3. AUC0-8 for plasma Al from 0 to 8 hours was significantly greater (p less than 0.05) for Al(OH)3 + sodium citrate/citric acid (73 +/- 23 micrograms.hr/l; mean +/- SEM) than Al(OH)3 (16 +/- 30 micrograms.hr/l); sodium citrate/citric acid (-27 +/- 14 micrograms.hr/l); or Al(OH)3 + NaHCO3 (6 +/- 22 micrograms.hr/l). The 24 hour Al level remained above baseline (p less than 0.03) following Al(OH)3 + sodium citrate/citric acid (31 +/- 12 (pre) vs 54 +/- 14 micrograms/l (post), in contradistinction to study limb: l (34 +/- 14 vs 30 +/- 12 micrograms/l); III (79 +/- 40 vs 65 +/- 35 micrograms/l); and IV (71 +/- 37 vs 66 +/- 42 micrograms/l). We conclude that the GI absorption of Al from Al(OH)3 is enhanced by citrate in patients undergoing hemodialysis and that elevations of plasma Al persist longer. The concomitant administration of citrate and Al-containing phosphate (PO4) binders should be avoided in patients with end-stage renal disease (ESRD). NaHCO3 may serve as an alternative therapy for metabolic acidosis with less risk of enhancing Al absorption.