Mechanism for higher urine pH in normal women compared with men.

Regulation of acid-base metabolism maintains the pH of body fluids within a tight range. Urine pH (UpH) is also regulated under normal conditions. Median pH of 24-h urines is ~6, but others have noted that UpH in women is higher than men, which has been attributed to differences in diet. If true, it would help to explain the fact that calcium phosphate stones, which form at higher urine pH, are much more common in women than in men. We studied 14 normal subjects (7 men and 7 women) fed identical meals in a Clinical Research Center. Urine and blood samples were collected during fasting and after meals. UpH of women (6.74 ± 0.11) exceeded that of men (6.07 ± 0.17) fed, but not fasting, and UpH rose significantly with meals in women but not men. Serum and urine total CO2 rose with meals in women but not men, and in women net acid excretion fell to zero during the fed period. In a general linear model adjusted for age, sex, and weight, net gastrointestinal anion uptake was the main predictor of UpH and was significantly higher in women (3.9 ± 0.6) than men (1.8 ± 0.7) in the fed period. Urine citrate, an anion absorbed by the gastrointestinal tract, was higher in women than men in the fed state, and fractional excretion of citrate was higher in women than men. The higher fed UpH in women is related to a greater absorption of food anions and raises 24-h UpH.

Lithium increases ammonium excretion leading to altered urinary acid-base buffer composition.

Previous reports identify a voltage dependent distal renal tubular acidosis (dRTA) secondary to lithium (Li+) salt administration. This was based on the inability of Li+-treated patients to increase the urine-blood (U-B) pCO2 when challenged with NaHCO3 and, the ability of sodium neutral phosphate or Na2SO4 administration to restore U-B pCO2 in experimental animal models. The underlying mechanisms for the Li+-induced dRTA are still unknown. To address this point, a 7 days time course of the urinary acid-base parameters was investigated in rats challenged with LiCl, LiCitrate, NaCl, or NaCitrate. LiCl induced the largest polyuria and a mild metabolic acidosis. Li+-treatment induced a biphasic response. In the first 2 days, proper urine volume and acidification occurred, while from the 3rd day of treatment, polyuria developed progressively. In this latter phase, the LiCl-treated group progressively excreted more NH4+ and less pCO2, suggesting that NH3/NH4+ became the main urinary buffer. This physiological parameter was corroborated by the upregulation of NBCn1 (a marker of increased ammonium recycling) in the inner stripe of outer medulla of LiCl treated rats. Finally, by investigating NH4+ excretion in ENaC-cKO mice, a model resistant to Li+-induced polyuria, a primary role of the CD was confirmed. By definition, dRTA is characterized by deficient urinary ammonium excretion. Our data question the presence of a voltage-dependent Li+-induced dRTA in rats treated with LiCl for 7 days and the data suggest that the alkaline urine pH induced by NH3/NH4+ as the main buffer has lead to the interpretation dRTA in previous studies.

Measurement of total CO2 in microliter samples of urine and other biological fluids using infrared detection of CO2.

The purpose of this study is to describe a low-cost and simply made instrument capable of measuring the total CO2 content of microliter volumes of biological fluids utilizing a commercially available CO2 sensor based on a NDIR detector. The described instrument is based on transformation of dissolved HCO3- to CO2 by acidification and subsequent measurement of the produced CO2. The instrument has a linear response in the range 0.025-10 µmol HCO3-, which enables measurements in fresh urine and plasma samples down to 5 µl. The values from plasma were compared to measurements made on 65 µl whole blood in an automatic blood gas analyzer and found not to differ significantly. Compared to currently commercially available instruments applying the same principles to measure total CO2, this study provides a simple and robust alternative which even can be used on smaller sample volumes.

The Cornell Net Carbohydrate and Protein System: Updates to the model and evaluation of version 6.5.

New laboratory and animal sampling methods and data have been generated over the last 10 yr that had the potential to improve the predictions for energy, protein, and AA supply and requirements in the Cornell Net Carbohydrate and Protein System (CNCPS). The objectives of this study were to describe updates to the CNCPS and evaluate model performance against both literature and on-farm data. The changes to the feed library were significant and are reported in a separate manuscript. Degradation rates of protein and carbohydrate fractions were adjusted according to new fractionation schemes, and corresponding changes to equations used to calculate rumen outflows and postrumen digestion were presented. In response to the feed-library changes and an increased supply of essential AA because of updated contents of AA, a combined efficiency of use was adopted in place of separate calculations for maintenance and lactation to better represent the biology of the cow. Four different data sets were developed to evaluate Lys and Met requirements, rumen N balance, and milk yield predictions. In total 99 peer-reviewed studies with 389 treatments and 15 regional farms with 50 different diets were included. The broken-line model with plateau was used to identify the concentration of Lys and Met that maximizes milk protein yield and content. Results suggested concentrations of 7.00 and 2.60% of metabolizable protein (MP) for Lys and Met, respectively, for maximal protein yield and 6.77 and 2.85% of MP for Lys and Met, respectively, for maximal protein content. Updated AA concentrations were numerically higher for Lys and 11 to 18% higher for Met compared with CNCPS v6.0, and this is attributed to the increased content of Met and Lys in feeds that were previously incorrectly analyzed and described. The prediction of postruminal flows of N and milk yield were evaluated using the correlation coefficient from the BLUP (R(2)BLUP) procedure or model predictions (R(2)MDP) and the concordance correlation coefficient. The accuracy and precision of rumen-degradable N and undegradable N and bacterial N flows were improved with reduced bias. The CNCPS v6.5 predicted accurate and precise milk yield according to the first-limiting nutrient (MP or metabolizable energy) with a R(2)BLUP=0.97, R(2)MDP=0.78, and concordance correlation coefficient=0.83. Furthermore, MP-allowable milk was predicted with greater precision than metabolizable energy-allowable milk (R(2)MDP=0.82 and 0.76, respectively, for MP and metabolizable energy). Results suggest a significant improvement of the model, especially under conditions of MP limitation.

Distal Renal Tubular Acidosis Screening by Urinary Acidification Testing in Mexican Children.

BACKGROUND: Primary distal renal tubular acidosis is a clinical disorder characterized by hyperchloremic metabolic acidosis, hypercalciuria, hypocitraturia, urinary acidification impairment, hypokalemia, metabolic bone disease, and nephrocalcinosis. Urinary acidification ability may be evaluated by an acidification test or maximum urinary pCO2 assessment with alkaline urine. The maximum urinary pCO2 test using acetazolamide and sodium bicarbonate is an easy test to confirm the lack of urine acidification in distal renal tubular acidosis in children. OBJECTIVE: To determine the urinary acidification ability using the maximum urinary pCO2 assessment in a group of children with a distal renal tubular acidosis diagnosis. MATERIAL AND METHODS: Thirty children were evaluated (13 males and 17 females); 23 children had been diagnosed with distal renal tubular acidosis by other physicians and were under alkali treatment with potassium and sodium citrates (21) and bicarbonate (2), and five children were not under alkali treatment. Two children had been diagnosed with primary distal renal tubular acidosis by our medical group. The maximum urinary pCO2 was determined by the oral intake of acetazolamide and sodium bicarbonate. RESULTS: Two cases with primary distal renal tubular acidosis were found, and they had a history of dehydration episodes during infancy and showed hyperchloremic metabolic acidosis with hypokalemia. They also exhibited urine acidification impairment with furosemide and reduced urinary pCO2 (< 60 mmHg), and the urine-blood pCO2 gradient was reduced in both cases (< 30 mmHg). One of them developed bilateral sensorineural deafness, while the other showed severe hypocitraturia. One case of proximal or type 2 renal tubular acidosis with hyperaminoaciduria was identified. Twenty-eight children displayed normal urinary acidification and did not show signs of distal renal tubular acidosis. CONCLUSIONS: The urinary acidification test with furosemide and urinary pCO2 assessment are reliable tests to identify the renal excretion of hydrogen ions (H+) and allow confirmation of the lack of urine acidification in distal renal tubular acidosis.

Microfluidic optoelectronic sensor for salivary diagnostics of stomach cancer.

We present a microfluidic optoelectronic sensor for saliva diagnostics with a potential application for non-invasive early diagnosis of stomach cancer. Stomach cancer is the second most common cause of cancer-related deaths in the world. The primary identified cause is infection by a gram-negative bacterium Helicobacter pylori. These bacteria secrete the enzyme urease that converts urea into carbon dioxide (CO2) and ammonia (NH3), leading to their elevated levels in breath and body fluids. The proposed optoelectronic sensor will detect clinically relevant levels of CO2 and NH3 in saliva that can potentially be used for early diagnosis of stomach cancer. The sensor is composed of the embedded in a microfluidic device array of microwells filled with ion-exchange polymer microbeads doped with various organic dyes. The optical response of this unique highly diverse sensor is monitored over a broad spectrum, which provides a platform for cross-reactive sensitivity and allows detection of CO2 and NH3 in saliva at ppm levels.

Clinical and biochemical findings in Mexican patients with distal renal tubular acidosis.

INTRODUCTION: Renal tubular acidosis (RTA) is a rare disease characterized by a normal serum anion gap, sustained metabolic acidosis, low concentration of plasma bicarbonate, variable hyperchloremia and hypokalemia and conserved glomerular filtration rate. RTA is developed during the first year of life and produces failure to thrive and anorexia. Primary distal RTA (type 1) is a renal syndrome with a reduced ability to excrete the acid load through the collecting ducts and impairment to concentrate the urine causing polyuria and dehydration. OBJECTIVE: Evaluate the current health status and describe the clinical findings and progress of Mexican patients with distal RTA. Demonstrate the distal urinary acidification defect by measuring the urinary pCO2 tension in alkaline urines. MATERIAL AND METHODS: We looked for infants in tertiary care hospitals with a clinical history of normal serum anion gap, metabolic acidosis, hypokalemia, hyperchloremia, nephrocalcinosis, sensorineural hearing loss and inability for urine acidification under systemic metabolic acidosis. Biochemical analysis were performed periodically. Alkali medication was not suspended in one patient to assess urinary acidification with oral administration of sodium bicarbonate (2 mEq/Kg) and acetazolamide (500 mg/1.73 m2 body surface). Urinary pCO2 levels were determined at 60 and 90 min. RESULTS: Three children, one adolescent and one adult with distal RTA were found. They had an infant history of dehydration, failure to thrive, anorexia, vomiting, muscle paralysis, hypercalciuria, urinary infections, polyuria, polydipsia and polyhidramnios during pregnancy. Severe nephrocalcinosis was detected in all patients whereas sensorineural hearing loss was developed in four cases. Under the alkali medication all cases but one were normocalciuric. A patient developed kidney failure. The urinary acidification test confirmed the innability to eliminate the acid load. CONCLUSION: Early diagnosis in infancy and continuos alkali medication were of great benefit for most of the patients. Urinary pCO2 levels in alkaline urine provided an index for collecting duct hydrogen-ion secretion. To our knowledge this is the first report of mexican patients with distal RTA.

Evaluation of gut bacterial populations using an electronic e-nose and field asymmetric ion mobility spectrometry: further insights into 'fermentonomics'.

The fermentation of undigested foods in the large bowel, by its resident bacteria, results in the production of several chemicals including volatile gases. Perturbance in gut bacteria is known to influence colonic and metabolic health, but to determine this requires prolonged culture (often unsuccessful) or expensive genomic sequencing. Clearly this is not practical for daily clinical practice. Previously, we have reported our insights into fermentonomics through the detection of volatile organic compounds (VOCs) in patients with gastrointestinal and metabolic diseases, using the electronic nose. In this paper we report on the changes in the fermentone produced by patients undergoing complete versus partial bowel cleansing. Using urine samples, preliminary results from 23 individuals receiving bowel cleansing indicate the ability of the electronic nose to distinguish between the partial and complete procedures. Moreover in a subset of individuals, we have been able to track evolving bacterial recolonization over time using the e-nose and field asymmetric ion mobility spectrometry (FAIMS). Such an approach has practical application in tracking bacterial dysbiosis following perturbation.

Does the exposure of urine samples to air affect diagnostic tests for urine acidification?

BACKGROUND AND OBJECTIVES: For accurate measurement of pH, urine collection under oil to limit the escape of CO(2) on air exposure is recommended. This study aims to test the hypothesis that urine collection under oil is not necessary in acidic urine in which bicarbonate and CO(2) are minor buffers, because loss of CO(2) would have little effect on its pH. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: One hundred consecutive random urine samples were collected under oil and analyzed for pH, pCO(2), and HCO(3)(-) immediately and after 5 minutes of vigorous shaking in uncovered flasks to allow CO(2) escape. RESULTS: The pH values in 97 unshaken samples ranged from 5.03 to 6.83. With shaking, urine pCO(2) decreased by 76%, whereas urine HCO(3)(-) decreased by 60%. Meanwhile, urine baseline median pH (interquartile range) of 5.84 (5.44-6.25) increased to 5.93 (5.50-6.54) after shaking (ΔpH=0.12 [0.07-0.29], P<0.001). ΔpH with pH≤6.0 was significantly lower than the ΔpH with pH>6.0 (0.08 [0.05-0.12] versus 0.36 [0.23-0.51], P<0.001). Overall, the lower the baseline pH, the smaller the ΔpH. CONCLUSIONS: The calculation of buffer reactions in a hypothetical acidic urine predicted a negligible effect on urine pH on loss of CO(2) by air exposure, which was empirically proven by the experimental study. Therefore, exposure of urine to air does not substantially alter the results of diagnostic tests for urine acidification, and urine collection under oil is not necessary.

Clinical approach to renal tubular acidosis in adult patients.

Renal tubular acidosis (RTA) is a group of disorders observed in patients with normal anion gap metabolic acidosis. There are three major forms of RTA: A proximal (type II) RTA and two types of distal RTAs (type I and type IV). Proximal (type II) RTA originates from the inability to reabsorb bicarbonate normally in the proximal tubule. Type I RTA is associated with inability to excrete the daily acid load and may present with hyperkalaemia or hypokalaemia. The most prominent abnormality in type IV RTA is hyperkalaemia caused by hypoaldosteronism. This article extensively reviews the mechanism of hydrogen ion generation from metabolism of normal diet and various forms of RTA leading to disruptions of normal acid-base handling by the kidneys.

Doubly labeled water analysis using cavity ring-down spectroscopy.

The doubly labeled water method provides an objective and accurate measure of total energy expenditure in free-living subjects and is considered the gold-standard method for this measurement. Its use, however, is limited by the need to employ isotope ratio mass spectrometry (IRMS) to obtain the high-precision isotopic abundance analyses needed to optimize the dose of expensive (18) O-labeled water. Recently, cavity-ring down spectroscopy (CRDS) instruments have become commercially available and may serve as a less expensive alternative to IRMS. We compared the precision and accuracy of CRDS with those of IRMS for the measurement of total energy expenditure from urine specimens in 14 human subjects. The relative accuracy and precision (SD) for total body water was 0.5 ± 1% and for total energy expenditure was 0.5 ± 6%. The CRDS instrument displayed a memory between successive specimens of 5% for (18) O and 9% for (2) H. The memory necessitated carefully ordering of specimens to reduce isotopic disparity, performance of several injections of each specimen to condition the analyzer, and use of a mathematical memory correction on subsequent injections. These limited the specimen throughput to about one urine specimen per hour. CRDS provided accuracy and precision for isotope abundance measurements of urine that were comparable with those of IRMS. The memory problems were easily recognized by our experienced laboratory staff, but future efforts should be aimed at reducing the memory of the CRDS so that it would be less likely to result in poor reproducibility in laboratories using doubly labeled water for the first time.

Quantification of carbonate by gas chromatography-mass spectrometry.

Carbon dioxide and carbonates are widely distributed in nature, are constituents of inorganic and organic matter, and are essential in vegetable and animal organisms. CO(2) is the principal greenhouse gas in the atmosphere. In human blood, CO(2)/HCO(3)(-) is an important buffering system. Quantification of bicarbonate and carbonate in inorganic and organic matter and in biological fluids such as blood or blood plasma by means of the GC-MS technology has been impossible so far, presumably because of the lack of suitable derivatization reactions to produce volatile and thermally stable derivatives. Here, a novel derivatization reaction is described for carbonate that allows for its quantification in aqueous alkaline solutions and alkalinized plasma and urine. Carbonate in acetonic solutions of these matrices (1:4 v/v) and added (13)C-labeled carbonate for use as the internal standard were heated in the presence of the derivatization agent pentafluorobenzyl (PFB) bromide for 60 min and 50 °C. Investigations with (12)CO(3)(2-), (13)CO(3)(2-), (CH(3))(2)CO, and (CD(3))(2)CO in alkaline solutions and GC-MS and GC-MS/MS analyses under negative-ion chemical ionization (NICI) or electron ionization (EI) conditions of toluene extracts of the reactants revealed formation of two minor [i.e., PFB-OCOOH and O=CO(2)-(PFB)(2)] and two major [i.e., CH(3)COCH(2)-C(OH)(OPFB)(2) and CH(3)COCH=C(OPFB)(2)] carbonate derivatives. The latter have different retention times (7.9 and 7.5 min, respectively) but virtually identical EI and NICI mass spectra. It is assumed that CH(3)COCH(2)-C(OH)(OPFB)(2) is formed from the reaction of the carbonate dianion with two molecules of PFB bromide to form the diPFB ester of carbonic acid, which further reacts with one molecule of acetone. Subsequent loss of water finally generates the major derivative CH(3)COCH=C(OPFB)(2). This derivatization reaction was utilized to quantify total CO(2)/HCO(3)(-)/CO(3)(2-) (tCO(2)) in human plasma and urine by GC-MS in the NICI mode by selected ion monitoring of the anions [M-H](-) of CH(3)COCH=C(OPFB)(2) at m/z 461 for the endogenous species and m/z 462 for the internal standard (13)CO(3)(2-). Oral intake of the carboanhydrase inhibitor drug acetazolamide by two healthy volunteers resulted in temporary increased excretion of tCO(2) in the urine. The method is specific for carbonate, accurate, sensitive and should be applicable to various matrices including human fluids and environmental samples.

Is the pattern of solid-phase gastric emptying different between genders?

BACKGROUND: In the 13C-octanoate breath test, the shape of the 13CO2 excretion curve in the ascending portion reflects a pattern of gastric emptying (GE). Recent scintigraphic studies have revealed an overall delay in solid GE in fertile women compared with men. However, it remains unknown whether women have a different GE pattern compared with men. As a symptomatic delay in solid GE is specific to the female gender, it could be hypothesized that the 13CO2 excretion curve is different in shape between genders. MATERIALS AND METHODS: Because the ascending gradient of the 13CO2 excretion curve is often biphasic, the dual function of y(t) = ( a1 . tb1 + a2 . tb2) e(-K.t) was applied to fit the breath data, where a1, b1, a2, b2, and K are constants. Assessed on the 4 h-based breath samples obtained after ingestion of a 320-kcal muffin containing 100 mg 13C-octanoate, the time versus 13CO2 excretion curve was created from 31 adult volunteers (15 men and 16 women). The curve shape was characterized by the dual function, and was compared between genders. RESULTS: In both genders, the ascending gradient exhibited the biphasic feature, characterized by an initial steep rise and the subsequent blunted increase, while the descending gradient followed the monotonous decay. The initial rise was steeper and the subsequent increase was more blunted in women than in men. CONCLUSION: Women exhibit a gender-specific pattern of the 13CO2 excretion profile. A possible explanation for this gender difference is that the post-gastric feedback regulation is more potent in women than in men.

Short-term emissions of ammonia and carbon dioxide from cattle urine contaminated tropical grassland microcosm.

The study was designed to understand the emissions of ammonia (NH(3)) and carbon dioxide (CO(2)) from a single cattle urination event on a tropical grassland and underline the significance of the emissions in the context of huge animal population grazing on large pasture areas in some countries. Emissions of ammonia (NH(3)) and carbon dioxide (CO(2)) were monitored for three weeks from a tropical grassland (dominated by Cynodon dactylon Pers.) microcosm contaminated with cow and buffalo urine. The grassland microcosms were treated with urine (50 and 100 ml of each) only once and irrigated with water once every week. Ammonia was sampled by an automatic sampling system comprising of a vacuum pump, three-way stopcocks and rubber tubing and an impinger containing suitable absorbing solution (H(2)SO(4)), connected to the tubing suitably. The sampled gas, after sucked by the vacuum pump and absorbed in H(2)SO(4), was allowed to enter the closed microcosm again maintaining internal pressure of the microcosm. Carbon dioxide was sampled by absorption in an alkali (NaOH) trap inside the microcosm. Both NH(3) and CO(2) emissions were highly variable temporally and there was no continuous increasing or decreasing emission trend with time. Respectively, 45 and 46% of total NH(3)-N were emitted within first 48 h from 50 and 100 ml cow urine application while the corresponding values for buffalo urine were 34 and 32%. Total NH(3)-N emissions, integrated for sampling days (i.e. 1, 2, 3, 4, 6, 15, 18 and 21st) were 11 and 6% in cow and 8 and 5% in buffalo urine, of the total-N added through 50 and 100 ml urine samples. Carbon dioxide emissions were standardized at 25 degrees C by using a suitable formula which were lower than actual emissions at actual soil temperature (> 25 degrees C). Carbon dioxide emission rates were classified on the basis of soil repiratory classification and classes ranged from moderately low soil activity up to unusually high soil activity, the latter observed only on very few sampling days. Grasses in the microcosm had shown appreciable growth after urine application. Although variable and somewhat unpredictable, emissions were appreciable and that too only from a patch of single urination, indicating to the huge magnitude of total emissions under the scenario of thousands of cattle grazing on hundreds of acres of grasslands in a tropical country.

Food mineral composition and acid-base balance in rabbits.

BACKGROUND: Alkali-rich diets are often recommended in human medicine to prevent the pathological consequences of nutritional acid load in conditions of impaired renal function. AIM OF THE STUDY: This study was undertaken in rabbits as common laboratory animals for basic medical research to explore the impact of high versus low dietary alkali intake on systemic acid-base balance and renal control in a typical herbivore. METHODS: Male rabbits (2.3-4.8 kg) were kept in a metabolism cage. The 24h urine and arterial blood samples were analysed for acid-base data. The metabolic CO2 production was measured to calculate alveolar ventilation. Three randomized groups of animals were fed ad libitum with rabbit chow providing sufficient energy but variable alkali load, assessed by the ashes' cation-anion difference. RESULTS: The average daily nutritional alkali load (+/- SEM) was 67.1 +/- 2.2 mEq x kg(-1) (N = 58) in the group on high, 45.4 +/- 2.5 mEq x kg(-1) (N = 31) in the group on normal and 1.7 +/- 0.5 mEq x kg(-1) (N = 11) in the group on low alkali food. Respective mean arterial base excess values (BE) were 1.4 +/- 0.3 mM, 0.3 +/- 0.4 mM and 0.0 +/- 0.3 mM, being significantly higher on high alkali food (P < 0.05) than in the other groups. Arterial PCO2, alveolar ventilation and metabolic CO2 production were not significantly different between groups. On normal and high-alkali chow, an alkaline urine (pH(u) > 8.0) with 18-20 mmol x kg(-1) bicarbonate/carbonate was excreted daily, typically containing an insoluble precipitate of 35-60% carbonate. On low-alkali diet, the mean pH(u) decreased to 6.26 +/- 0.14, due to a strong reduction of daily excreted soluble bicarbonate and precipitated carbonate to 1.2 +/- 0.6 and 0.7 +/- 0.2 mmol x kg(-1), respectively. Thereby, nearly complete fractional base reabsorption of 97.8 +/- 0.7 % was reached. CONCLUSION: Herbivore nutritional alkali-load elicited large rates of renal base excretion including precipitates, to which the urinary tract of the rabbits appeared to be adapted. Dietary base variations were more accurately reflected in the urine than by the blood acid-base status. A strongly base-deficient diet exerted maximum impact on renal base saving mechanisms, implying a critical precondition for growing susceptibility to metabolic acidosis also in the rabbit.

The urine-blood PCO gradient as a diagnostic index of H(+)-ATPase defect distal renal tubular acidosis.

BACKGROUND: Urine pH during acidemia and urine PCO2 upon alkalization both may be useful to indicate H+ secretion from collecting ducts. The urine anion gap has been used to detect urinary NH4+ for differential diagnosis of hyperchloremic metabolic acidosis. We have previously demonstrated that the lack of normal H(+)-ATPase may underlie secretory defect distal renal tubular acidosis (dRTA). In this study we evaluated the diagnostic value of the urine-blood (U-B) PCO2 in H(+)-ATPase defect dRTA, and compared it with that of urine pH and urine anion gap during acidemia. METHODS: In H(+)-ATPase defect dRTA, the diagnostic values of three urinary parameters were evaluated: (1) urine pH measured after acid (NH4Cl) loading; (2) urine-to-blood carbon dioxide tension gradient (U-B PCO2) during alkali (NaHCO3) loading; and (3) urine anion gap during acidemia. Seventeen patients were diagnosed as having H(+)-ATPase defect dRTA based on reduced urinary NH4+ and an absolute decrease in H(+)-ATPase immunostaining in intercalated cells on renal biopsy. Eight patients with non-dRTA renal disease served as control patients. RESULTS: Upon NaHCO3 loading, U-B PCO2 was < or =30 mm Hg in all 17 dRTA patients and >30 mm Hg in all 8 control patients. With NH4Cl loading, urine pH was >5.4 in 15 of 17 dRTA patients and < or =5.4 in 7 of 8 control patients, and the urine anion gap was >5 mmol/L in 13 of 17 dRTA patients and< or =5 mmol/L in 6 of 8 control patients. Therefore, the sensitivity and specificity of U-B PCO2 < or =30 mm Hg during NaHCO3 loading were both 100%, whereas those of urine pH >5.4 or urine anion gap >5 mmol/L during NH4Cl loading were below 90%. In control patients, the U-B PCO2 was found to be well correlated with the urinary NH4+ (r= 0.79, P < 0.05). CONCLUSION: The U-B PCO2 during NaHCO3 loading is an excellent diagnostic index of H(+)-ATPase defect dRTA.

13C urea breath test (UBT) in the diagnosis of Helicobacter pylori: why does it work better with acid test meals?

BACKGROUND: Acid test meals may improve the accuracy of the (13)C urea breath test (UBT). This has been attributed to changes in gastric emptying rather than to the effects of gastric pH on Helicobacter pylori urease. AIMS: To determine whether enhancement of (13)CO(2) excretion in the UBT in H pylori infected volunteers by acidification of a test meal is due to a delay in gastric emptying. METHODS: Urease activity in vitro was measured in intact bacteria and in bacterial homogenates. Urease activity in vivo was assessed by means of the UBT. Eleven H pylori infected subjects underwent UBTs with neutral Ensure (pH 7.0), acidified Ensure (pH 3.0), and apple juice (pH 3.0). Gastric emptying was assessed by (13)C sodium acetate breath test. RESULTS: From pH 7 to pH 3, the in vitro urease activity of intact bacteria increased sixfold. In contrast, urease activity of bacterial homogenates was inactivated by low pH. In vivo, urease activity, as measured by the UBT 20 minutes after meal ingestion, was higher with apple juice (delta (13)CO(2)=21.1; p=0.03) and acidified Ensure (delta (13)CO(2)=25.5; p=0.01) than with neutral Ensure (delta (13)CO(2)=12.5). Gastric emptying was faster with apple juice (T(max)=36.7 (8) minutes) but not with acidified Ensure (T(max)=63.3 (5) minutes; p=0.06) than with neutral Ensure (T(max)=65.0 (3) minutes; p=0.04). CONCLUSIONS: The higher UBT found with acidified compared with neutral test meals was independent of the emptying rates of the test meals but may have been due to medium acidity dependent activation of intra-bacterial urease in intact H pylori.

Comparison of recoveries in breath carbon dioxide of H13CO-3 and H14CO-3 administered simultaneously by single 6 h constant unprimed intravenous infusion.

The aim of this study was to assess the bioequivalence of H13CO-3 and H14CO-3, by administering both labels simultaneously by single infusion and comparing their recovery in breath CO2 and urinary urea. Six healthy male subjects (age range 24-41 years; weight 76.7 (sd, 18.6) kg; height 1.79 (sd 0.05) m) were infused with unprimed solutions of HCO3- (110.0 mmol/kg) labelled with 13C (0.76 mmol 13C/h) and 14C (48 Bq/h) at a constant rate for 6 h, in a whole-body calorimeter (1400 litres) for measurement of CO2 production. Samples of breath were collected hourly in a Douglas bag and all urine was collected into two batches (0-4 h and 4-6 h) for estimating recovery of infused label by measurement of enrichment or specific activity. Recovery in breath CO2 of both labels increased from about 25 % for the first hour to 88 % and above for hours 3-4 onwards. Mean recovery of 13C in breath CO2 was slightly higher than that of 14C for all periods (mean difference always less than 1 % of infused label) but was significant only for the first 3 h (P < 0.05). Recovery of 14C in urea was significantly higher (P < 0.01) than 13C, but was confounded by substantial variability and uncertainties concerning 13CO2 background enrichments. These results suggest that there is no compelling need to alter factors currently used for recovery of 14C in breath when using 13C instead, and vice versa.

Hypercalciuria and recurrent urinary tract infection in Venezuelan children.

Recurrent urinary tract infection (UTI) has not been widely recognized as a clinical manifestation of hypercalciuria in children. We studied 59 children with two or more episodes of UTI, a normal urinary tract, and with hypercalciuria. Clinical manifestations were fever, dysuria, straining with micturition, hematuria, polyuria, abdominal pain, and failure to thrive. Urinary calcium/creatinine ratio was 0.36+/-0.15 mg/mg. Renal function studies included serum bicarbonate (21+/-3 mmol/l), urinary/blood PCO2 difference (11+/-11 mmHg), urinary net acid excretion (63+/-3 micromol/min per 1.73 m2), uric acid fractional excretion (13%+/-12%), and maximal urinary osmolality (920+/-236 mosmol/kg). Treatment included promotion of fluid intake, avoiding excessive salt and protein, and keeping dietary calcium between 900 and 1,200 mg/day. Potassium citrate or hydrochlorothiazide were indicated if hypercalciuria persisted. With this treatment, in 95% of the children, no further episodes of UTI occurred once normocalciuria was achieved. It is possible that hypercalciuria may play a predisposing role for recurrent UTI in children by promoting the formation of microcrystals which damage the uroepithelium. We advocate the investigation of urinary calcium excretion in children with recurrent UTI and a normal urinary tract.

Distal renal tubular acidosis and high urine carbon dioxide tension in a patient with southeast Asian ovalocytosis.

Southeast Asian ovalocytosis (SAO) is the best-documented disease in which mutation in the anion exchanger-1 (AE1) causes decreased anion (chloride [Cl-]/bicarbonate [HCO3-]) transport. Because AE1 is also found in the basolateral membrane of type A intercalated cells of the kidney, distal renal tubular acidosis (dRTA) might develop if the function of AE1 is critical for the net excretion of acid. Studies were performed in a 33-year-old woman with SAO who presented with proximal muscle weakness, hypokalemia (potassium, 2.7 mmol/L), a normal anion gap type of metabolic acidosis (venous plasma pH, 7. 32; bicarbonate, 17 mmol/L; anion gap, 11 mEq/L), and a low rate of ammonium (NH4+) excretion in the face of metabolic acidosis (26 micromol/min). However, the capacity to produce NH4+ did not appear to be low because during a furosemide-induced diuresis, NH4+ excretion increased almost threefold to a near-normal value (75 micromol/L/min). Nevertheless, her minimum urine pH (6.3) did not decrease appreciably with this diuresis. The basis of the renal acidification defect was most likely a low distal H+ secretion rate, the result of an alkalinized type A intercalated cell in the distal nephron. Unexpectedly, when her urine pH increased to 7.7 after sodium bicarbonate administration, her urine minus blood carbon dioxide tension difference (U-B Pco2) was 27 mm Hg. We speculate that the increase in U-B Pco2 might arise from a misdirection of AE1 to the apical membrane of type A intercalated cells.