Automatic real-time analysis and interpretation of arterial blood gas sample for Point-of-care testing: Clinical validation.

BACKGROUND: Point-of-care arterial blood gas (ABG) is a blood measurement test and a useful diagnostic tool that assists with treatment and therefore improves clinical outcomes. However, numerically reported test results make rapid interpretation difficult or open to interpretation. The arterial blood gas algorithm (ABG-a) is a new digital diagnostics solution that can provide clinicians with real-time interpretation of preliminary data on safety features, oxygenation, acid-base disturbances and renal profile. The main aim of this study was to clinically validate the algorithm against senior experienced clinicians, for acid-base interpretation, in a clinical context. METHODS: We conducted a prospective international multicentre observational cross-sectional study. 346 sample sets and 64 inpatients eligible for ABG met strict sampling criteria. Agreement was evaluated using Cohen's kappa index, diagnostic accuracy was evaluated with sensitivity, specificity, efficiency or global accuracy and positive predictive values (PPV) and negative predictive values (NPV) for the prevalence in the study population. RESULTS: The concordance rates between the interpretations of the clinicians and the ABG-a for acid-base disorders were an observed global agreement of 84,3% with a Cohen's kappa coefficient 0.81; 95% CI 0.77 to 0.86; p < 0.001. For detecting accuracy normal acid-base status the algorithm has a sensitivity of 90.0% (95% CI 79.9 to 95.3), a specificity 97.2% (95% CI 94.5 to 98.6) and a global accuracy of 95.9% (95% CI 93.3 to 97.6). For the four simple acid-base disorders, respiratory alkalosis: sensitivity of 91.2 (77.0 to 97.0), a specificity 100.0 (98.8 to 100.0) and global accuracy of 99.1 (97.5 to 99.7); respiratory acidosis: sensitivity of 61.1 (38.6 to 79.7), a specificity of 100.0 (98.8 to 100.0) and global accuracy of 98.0 (95.9 to 99.0); metabolic acidosis: sensitivity of 75.8 (59.0 to 87.2), a specificity of 99.7 (98.2 to 99.9) and a global accuracy of 97.4 (95.1 to 98.6); metabolic alkalosis sensitivity of 72.2 (56.0 to 84.2), a specificity of 95.5 (92.5 to 97.3) and a global accuracy of 93.0 (88.8 to 95.3); the four complex acid-base disorders, respiratory and metabolic alkalosis, respiratory and metabolic acidosis, respiratory alkalosis and metabolic acidosis, respiratory acidosis and metabolic alkalosis, the sensitivity, specificity and global accuracy was also high. For normal acid-base status the algorithm has PPV 87.1 (95% CI 76.6 to 93.3) %, and NPV 97.9 (95% CI 95.4 to 99.0) for a prevalence of 17.4 (95% CI 13.8 to 21.8). For the four-simple acid-base disorders and the four complex acid-base disorders the PPV and NPV were also statistically significant. CONCLUSIONS: The ABG-a showed very high agreement and diagnostic accuracy with experienced senior clinicians in the acid-base disorders in a clinical context. The method also provides refinement and deep complex analysis at the point-of-care that a clinician could have at the bedside on a day-to-day basis. The ABG-a method could also have the potential to reduce human errors by checking for imminent life-threatening situations, analysing the internal consistency of the results, the oxygenation and renal status of the patient.

Metabolic Alkalosis in the Pediatric Patient: Treatment Options in the Pediatric ICU or Pediatric Cardiothoracic ICU Setting.

Metabolic alkalosis is characterized by the primary elevation of the serum bicarbonate concentration with a normal or elevated partial pressure of carbon dioxide. Although there may be several potential etiologies in the critically ill patient in the pediatric or cardiothoracic intensive care unit, metabolic alkalosis most commonly results from diuretic therapy with chloride loss. In most cases, the etiology can be determined by a review of the patient's history and medication record. Although generally innocuous with limited impact on physiologic function, metabolic alkalosis may impair central control of ventilation, especially when weaning from mechanical ventilation. The following manuscript presents the normal homeostatic mechanisms that control pH, reviews the etiology of metabolic alkalosis, and outlines the differential diagnosis. Options and alternatives for treatment including pharmacologic interventions are presented with a focus on these conditions as they pertain to the patient in the pediatric or cardiac intensive care unit.

Electrolyte and acid-base disorders in cancer patients and its impact on clinical outcomes: evidence from a real-world study in China.

Background: This study aims to delineate the incidence of electrolyte and acid-base disorders (EAD) in cancer patients, to figure out the risk factors of EAD, then to assess the impact of EAD on patients' in-hospital clinical outcomes.Methods: Patients with the diagnosis of malignancies hospitalized during 1 October 2014 and 30 September 2015 were recruited in Zhongshan Hospital, Fudan University in Shanghai of China. Demographic characteristics, comorbidities, and clinical data, including survival, length of stay and hospital cost, were extracted from the electronic medical record system. Electrolyte and acid-base data were acquired from the hospital laboratory database.Results: Of 25,881 cancer patients with electrolyte data, 15,000 (58.0%) cases had at least one electrolyte and acid-base abnormity. Hypocalcemia (27.8%) was the most common electrolyte disorder, followed by hypophosphatemia (26.7%), hypochloremia (24.5%) and hyponatremia (22.5%). The incidence of simple metabolic acidosis (MAC) and metabolic alkalosis (MAL) was 12.8% and 22.1% respectively. Patients with mixed metabolic acid-base disorders (MAC + MAL) accounted for 30.2%. Lower BMI score, preexisting hypertension and diabetes, renal dysfunction, receiving surgery/chemotherapy, anemia and hypoalbuminemia were screened out as the major risk factors of EAD. In-hospital mortality in patients with EAD was 2.1% as compared to those with normal electrolytes (0.3%). The risk of death significantly increased among patients with severe EAD. Similarly, the length of stay and hospital cost also tripled as the number and grade of EAD increased.Conclusion: EAD is commonly encountered in cancer patients and associated with an ominous prognosis. Patients with comorbidities, renal/liver dysfunction, and anti-tumor therapy have a higher risk of EAD. Regular monitoring of electrolytes, optimum regimen for intravenous infusion, timely correction of modifiable factors and appropriate management of EAD should not be neglected during anti-tumor treatment.

The arterial blood gas algorithm: Proposal of a systematic approach to analysis of acid-base disorders. / El algoritmo de la gasometría arterial: propuesta de un enfoque sistemático para el análisis de los trastornos del equilibrio ácido-base.

Abnormalities in the acid-base balance are common clinical problems and can have deleterious effects on cellular function and be a clue to various disorders. Therefore, it is important for the clinician to make a precise diagnosis of the acid-base disorder(s) present for a proper treatment. Three approaches have been proposed to evaluate acid-base disorders: a bicarbonate-centric approach; the Stewart approach, and the base excess approach. Although the latter two have many adherents, we will only discuss the bicarbonate-centric approach. This approach is simpler to utilize at the bedside, has a physiological evaluation of the acid-base disorder, presents an easily understandable approach to assess severity, and provides a more solid foundation for the development of effective therapies. Therefore, the following discussion will be limited to an examination of this approach. In this case-centric review, important new concepts will be introduced first; their benefits and limitations discussed; and then their utilization to analyze actual cases will be shown. A systematic approach algorithm that incorporates these new concepts has been generated and will be highlighted.

Water, electrolyte, acid-base, and trace elements alterations in cirrhotic patients.

Chronic hepatic patients, and particularly those suffering from cirrhosis, are predisposed to different sort of water, electrolyte, acid-base, and trace elements disorders due to their altered liver function, and also to their exposition to infectious, inflammatory, oncologic, and pharmacologic variables whose combination undermines their homeostatic capability. Hyponatremia, hypokalemia, hyperkalemia, hypocalcemia, metabolic acidosis, respiratory, and metabolic alkalosis are the main internal milieu alterations in this group.

Alkalosis and Dialytic Clearance of Phosphate Increases Phosphatase Activity: A Hidden Consequence of Hemodialysis.

BACKGROUND: Extracellular pyrophosphate is a potent endogenous inhibitor of vascular calcification, which is degraded by alkaline phosphatase (ALP) and generated by hydrolysis of ATP via ectonucleotide pyrophosphatase/phosphodiesterase 1 (eNPP1). ALP activity (as routinely measured in clinical practice) represents the maximal activity (in ideal conditions), but not the real activity (in normal or physiological conditions). For the first time, the present study investigated extracellular pyrophosphate metabolism during hemodialysis sessions (including its synthesis via eNPP1 and its degradation via ALP) in physiological conditions. METHODS AND FINDINGS: 45 patients in hemodialysis were studied. Physiological ALP activity represents only 4-6% of clinical activity. ALP activity increased post-hemodialysis by 2% under ideal conditions (87.4 ± 3.3 IU/L vs. 89.3 ± 3.6 IU/L) and 48% under physiological conditions (3.5 ± 0.2 IU/L vs. 5.2 ± 0.2 IU/L). Pyrophosphate synthesis by ATP hydrolysis remained unaltered post-hemodialysis. Post-hemodialysis plasma pH (7.45 ± 0.02) significantly increased compared with the pre-dialysis pH (7.26 ± 0.02). The slight variation in pH (~0.2 units) induced a significant increase in ALP activity (9%). Addition of phosphate in post-hemodialysis plasma significantly decreased ALP activity, although this effect was not observed with the addition of urea. Reduction in phosphate levels and increment in pH were significantly associated with an increase in physiological ALP activity post-hemodialysis. A decrease in plasma pyrophosphate levels (3.3 ± 0.3 µmol/L vs. 1.9 ± 0.1 µmol/L) and pyrophosphate/ATP ratio (1.9 ± 0.2 vs. 1.4 ± 0.1) post-hemodialysis was also observed. CONCLUSION: Extraction of uremic toxins, primarily phosphate and hydrogen ions, dramatically increases the ALP activity under physiological conditions. This hitherto unknown consequence of hemodialysis suggests a reinterpretation of the clinical value of this parameter.

Pseudohipoaldosteronismo y aparente exceso de mineralocorticoides: cara y ceca en dos pacientes pediátricos / Pseudohypoaldosteronism and apparent mineralocorticoid excess: two faces, two pediatric patients

Los síndromes endocrinológicos con hipofunción o hiperfunción con niveles paradójicos de dosajes hormonales han sido bien caracterizados en los últimos años del siglo XX, a partir del desarrollo de técnicas genéticas y moleculares. Presentamos dos pacientes con pseudohipoaldosteronismo y aparente exceso de mineralocorticoides como síndromes en espejo, con la intención de alertar al médico clínico respecto de su consideración como entidad diagnóstica en niños con alteraciones hidroelectrolíticas. (AU)

Endocrinological syndromes with underactive or overactive hormonal levels with paradoxical dosages have been well characterized over the years of the twentieth century, from the development of genetic and molecular techniques. We present two patients with pseudohypoaldosteronism and apparent mineralocorticoid excess as mirror syndromes, with the aim to alert the clinician regarding their consideration as a diagnostic entity in children with fluid and electrolyte disturbances. (AU)

Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition Study.

BACKGROUND AND OBJECTIVES: Low serum bicarbonate associates with mortality in CKD. This study investigated the associations of bicarbonate and acid-base status with mortality in healthy older individuals. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed data from the Health, Aging, and Body Composition Study, a prospective study of well functioning black and white adults ages 70-79 years old from 1997. Participants with arterialized venous blood gas measurements (n=2287) were grouped into <23.0 mEq/L (low), 23.0-27.9 mEq/L (reference group), and ≥28.0 mEq/L (high) bicarbonate categories and according to acid-base status. Survival data were collected through February of 2014. Mortality hazard ratios (HRs; 95% confidence intervals [95% CIs]) in the low and high bicarbonate groups compared with the reference group were determined using Cox models adjusted for demographics, eGFR, albuminuria, chronic obstructive pulmonary disease, smoking, and systemic pH. Similarly adjusted Cox models were performed according to acid-base status. RESULTS: The mean age was 76 years, 51% were women, and 38% were black. Mean pH was 7.41, mean bicarbonate was 25.1 mEq/L, 11% had low bicarbonate, and 10% had high bicarbonate. Mean eGFR was 82.1 ml/min per 1.73 m(2), and 12% had CKD. Over a mean follow-up of 10.3 years, 1326 (58%) participants died. Compared with the reference group, the mortality HRs were 1.24 (95% CI, 1.02 to 1.49) in the low bicarbonate and 1.03 (95% CI, 0.84 to 1.26) in the high bicarbonate categories. Compared with the normal acid-base group, the mortality HRs were 1.17 (95% CI, 0.94 to 1.47) for metabolic acidosis, 1.21 (95% CI, 1.01 to 1.46) for respiratory alkalosis, and 1.35 (95% CI, 1.08 to 1.69) for metabolic alkalosis categories. Respiratory acidosis did not associate with mortality. CONCLUSIONS: In generally healthy older individuals, low serum bicarbonate associated with higher mortality independent of systemic pH and potential confounders. This association seemed to be present regardless of whether the cause of low bicarbonate was metabolic acidosis or respiratory alkalosis. Metabolic alkalosis also associated with higher mortality.

Physicochemical evaluation of acid-base disorders after liver transplantation and the contribution from administered fluids.

OBJECTIVES: To analyze the mechanism of acid-base disorders in liver transplant recipients and to examine the relationship between these disorders and the fluids administered during surgery. METHODS: This prospective study in a university-affiliated hospital intensive care unit (ICU) included 52 patients admitted to the ICU from December 2009 to January 2011. We examined the contributions of inorganic ion differences, lactate, unmeasured anions, phosphate, and albumin to metabolic acidosis. In addition to laboratory variables, we collected demographic and clinical data. RESULTS: Metabolic acidosis (standard base excess ≤ -2.0 mmol/L) was identified in 37 (71.2%) patients during the immediate postoperative period. The inorganic ion difference was the main determinant of acidosis, accounting for -6.17 mEq/L of acidifying effect. The acidemia was attenuated mainly by the alkalinizing effect of albumin reduction, which contributed +6.03 mEq/L. There was an inverse proportional relationship between the quantity of saline solution used during surgery and the inorganic ion difference during the immediate postoperative period. CONCLUSIONS: Hyperchloremia is the primary contributor to metabolic acidosis in liver transplant recipients. Possibly the use of chloride-rich solutions increases the incidence of this disorder.

Prospective correlation of arterial vs venous blood gas measurements in trauma patients.

OBJECTIVE: The objective of this study is to assess if venous blood gas (VBG) results (pH and base excess [BE]) are numerically similar to arterial blood gas (ABG) in acutely ill trauma patients. METHODS: We prospectively correlated paired ABG and VBG results (pH and BE) in adult trauma patients when ABG was clinically indicated. A priori consensus threshold of clinical equivalence was set at ± less than 0.05 pH units and ± less than 2 BE units. We hypothesized that ABG results could be predicted by VBG results using a regression equation, derived from 173 patients, and validated on 173 separate patients. RESULTS: We analyzed 346 patients and found mean arterial pH of 7.39 and mean venous pH of 7.35 in the derivation set. Seventy-two percent of the paired sample pH values fell within the predefined consensus equivalence threshold of ± less than 0.05 pH units, whereas the 95% limits of agreement (LOAs) were twice as wide, at -0.10 to 0.11 pH units. Mean arterial BE was -2.2 and venous BE was -1.9. Eighty percent of the paired BE values fell within the predefined ± less than 2 BE units, whereas the 95% LOA were again more than twice as wide, at -4.4 to 3.9 BE units. Correlations between ABG and VBG were strong, at r(2) = 0.70 for pH and 0.75 for BE. CONCLUSION: Although VBG results do correlate well with ABG results, only 72% to 80% of paired samples are clinically equivalent, and the 95% LOAs are unacceptably wide. Therefore, ABG samples should be obtained in acutely ill trauma patients if accurate acid-base status is required.

Association of smoking, sleep apnea, and plasma alkalosis with nocturnal ventricular arrhythmias in men with systolic heart failure.

BACKGROUND: Excess sudden death due to ventricular tachyarrhythmias remains a major mode of mortality in patients with systolic heart failure. The aim of this study was to determine the association of nocturnal ventricular arrhythmias in patients with low ejection fraction heart failure. We incorporated a large number of known pathophysiologic triggers to identify potential targets for therapy to reduce the persistently high incidence of sudden death in this population despite contemporary treatment. METHODS: Eighty-six ambulatory male patients with stable low (≤ 45%) ejection fraction heart failure underwent full-night attendant polysomnography and simultaneous Holter recordings. Patients were divided into groups according to the presence or absence of couplets (paired premature ventricular excitations) and ventricular tachycardia (VT) (at least three consecutive premature ventricular excitations) during sleep. RESULTS: In multiple regression analysis, four variables (current smoking status, increased number of arousals, plasma alkalinity, and old age) were associated with VT and two variables (apnea-hypopnea index and low right ventricular ejection fraction) were associated with couplets during sleep. CONCLUSIONS: We speculate that cessation of smoking, effective treatment of sleep apnea, and plasma alkalosis could collectively decrease the incidence of nocturnal ventricular tachyarrhythmias and the consequent risk of sudden death, which remains high despite the use of ß blockades.

Perioperative metabolic alkalemia is more frequent than metabolic acidemia in major elective abdominal surgery.

OBJECTIVE: To investigate the incidence, type and etiology of perioperative metabolic disturbances associated with major abdominal surgery. We hypothesized that metabolic alkalemia is more frequent than metabolic acidemia. METHODS: This was a prospective, observational study, performed in a university-affiliated hospital. 98 consecutive patients undergoing major abdominal surgery were included in the study. Patients were observed by serial vital signs and laboratory measurements during the preoperative, intraoperative, PACU and the first three postoperative day periods. Central venous pressure, systolic pressure variation, fluid input, urine output, temper- ature, electrolytes, and acid-base variables were recorded. The primary endpoint of the study was the incidence of metabolic alkalemia or acidemia. Metabolic alkalemia was defined as pH >7.45 and BE >+3. Metabolic acidemia was defined as pH <7.35 and BE <-3. Continuous variables were described as mean ± standard deviation. Distributions of continuous variables was assessed for normalty using the Kolmogorov-Smirnov test (cut off at P = 0.01). The frequency of metabolic acidemia or alkalemia was compared across time points using Cochran's Q test and between time points using the binomial distribution. RESULTS: Metabolic acidemia occurred only intraoperatively and in the PACU. Subjects with metabolic acidemia were older, (74 ± 9 yr. vs. 66 ± 12, P = 0.01). Intraoperative body temperature was inversely associated with PACU lactate (P = 0.035). Blood loss >500 mL was more frequent in acidemic patients (42% vs. 19%, P = 0.033). More patients with hyperphosphatemia had acidemia than subjects without hyperphosphatemia (39% vs. 17%, P = 0.019). Metabolic alkalemia occurred more frequently than metabolic acidemia (49% vs. 23%, P < 0.0001) and was correlated with hypochloremia. The incidence of metabolic alkalemia decreased from baseline to intraoperative and PACU periods (13% vs. 3%, P = 0.003) and increased from the PACU to the three postoperative days (3% vs. 45%, P = 0.007). CONCLUSIONS: Metabolic alkalemia occurred more frequently than metabolic acidemia and occurred mainly preoperatively and postoperatively, while acidemia occurred mainly during surgery and in the PACU.

A mathematical model of tumour and blood pHe regulation: The HCO3-/CO2 buffering system.

Malignant tumours are characterised by a low, acidic extracellular pH (pHe) which facilitates invasion and metastasis. Previous research has proposed the potential benefits of manipulating systemic pHe, and recent experiments have highlighted the potential for buffer therapy to raise tumour pHe, prevent metastases, and prolong survival in laboratory mice. To examine the physiological regulation of tumour buffering and investigate how perturbations of the buffering system (via metabolic/respiratory disorders or changes in parameters) can alter tumour and blood pHe, we develop a simple compartmentalised ordinary differential equation model of pHe regulation by the HCO3-/CO2 buffering system. An approximate analytical solution is constructed and used to carry out a sensitivity analysis, where we identify key parameters that regulate tumour pHe in both humans and mice. From this analysis, we suggest promising alternative and combination therapies, and identify specific patient groups which may show an enhanced response to buffer therapy. In addition, numerical simulations are performed, validating the model against well-known metabolic/respiratory disorders and predicting how these disorders could change tumour pHe.

Negative exploration for pyloric stenosis--is it preventable?

BACKGROUND: The diagnosis of infantile hypertrophic pyloric stenosis (IHPS), although traditionally clinical, is now increasingly dependent on radiological corroboration. The rate of negative exploration in IHPS has been reported as 4%. The purpose of our study was to look at elements of supportive clinical evidence leading to positive diagnosis, and to review these with respect to misdiagnosed cases undergoing negative exploration. METHODS: All infants undergoing surgical exploration for IHPS between January 2000 and December 2004 were retrospectively analysed with regard to clinical symptoms, examination findings, investigations and operative findings. RESULTS: During the study period, 343 explorations were performed with a presumptive diagnosis of IHPS. Of these, 205 infants (60%) had a positive test feed, 269 (78%) had a positive ultrasound scan and 175 (55%) were alkalotic (pH >or=7.45 and/or base excess >or=2.5). The positive predictive value for an ultrasound (US) diagnosis was 99.1% for canal length >or=14 mm, and 98.7% for muscle thickness >or=4 mm. Four infants (1.1%) underwent a negative surgical exploration; Ultrasound was positive in 3, and negative in 1(who underwent surgery on the basis of a positive upper GI contrast). One US reported as positive had a muscle thickness <4 mm. Two false positive US were performed at peripheral hospitals. One infant had a false positive test feed following a positive ultrasound diagnosis. Two infants had negative test feeds. CONCLUSION: A 1% rate of negative exploration in IHPS compares favourably with other studies. However potential causes of error were identified in all 4 cases. Confident diagnosis comprises a combination of positive test feed and an 'in house US' in an alkalotic infant. UGI contrast study should not be used in isolation to diagnose IHPS. If the test feed is negative, strict diagnostic measurements should be observed on US and the pyloric 'tumour' palpated on table under anaesthetic before exploration.

Arterial blood gas analysis. 2: compensatory mechanisms.

This is the second of a two-part unit discussing arterial blood gas (ABG) analysis. Part 1 outlined background information on ABG reports and focused on a systematic approach to ABG analysis. This part examines the physiology of the various lines of defence in the body and explores the concept of compensation. A step-by-step guide to interpretation and examples of uncomplicated ABGs are available in the Portfolio Pages for this unit at nursingtimes.net, as well as further practice examples relevant to this part of the unit.

Making sense of blood gas results.

Recent technologic advances have allowed the production and marketing of cage-side blood gas analyzers to private practitioners. The widespread use of cage-side portable blood gas analyzers in veterinary practices has increased the need to develop the basic skills of blood gas analysis as part of a tool kit for practicing veterinarians. Rapid expansion of emergency and critical care medicine as a specialty and increased numbers of veterinary emergency and veterinary specialty practices have occurred concurrently with the availability of blood gas analyzers that are affordable for private practitioners. As a result, evaluation of blood gas results is no longer an activity confined to academic institutions and has become a daily part of many practicing veterinarians' activities.

[Arterial blood gas abnormalities during attacks of dizziness]. / Bas dönmesi ataklari sirasinda arteryel kan gazi anormallikleri.

OBJECTIVES: We investigated arterial blood gas abnormalities in patients presenting with dizziness. PATIENTS AND METHODS: The study included 58 patients (39 females, 19 males; mean age 46 years; range 22 to 74 years) who presented during attacks of dizziness. The duration of vertigo complaints ranged from one day to 30 years. Arterial gas measurements were performed at presentation and one month after treatment. The patients were examined in five groups according to the diagnoses: Meniere's disease (n=14), benign paroxysmal positional vertigo (n=13), vertebrobasilar insufficiency (n=12), vestibular neuritis (n=4), and craniocervical myofascial syndromes (n=15). RESULTS: At presentation, pH was low (acidosis) in two patients (3.5%), and high (alkalosis) in 15 patients (25.9%). After treatment, all abnormal pH values returned to normal. Twenty-four patients had high or low HCO3- values. High HCO3- values persisted in three patients together with dizziness. Patients with vestibular neuritis had significantly higher PO2 values compared to those with craniocervical myofascial syndrome and vertebrobasilar insufficiency (p<0.05). However, one month after treatment, there were no significant differences between five groups with respect to PO2 levels (p>0.05). Consecutive blood gas measurements did not differ significantly within each diagnosis group (p>0.05). CONCLUSION: Our results suggest that arterial blood gas abnormalities may be related to vertigo attacks.

Vacuolar H+-ATPase expression is increased in acid-secreting intercalated cells in kidneys of rats with hypercalcaemia-induced alkalosis.

AIMS: Hypercalcaemia is known to be associated with systemic metabolic alkalosis, although the underlying mechanism is uncertain. Therefore, we aimed to examine whether hypercalcaemia was associated with changes in the expression of acid-base transporters in the kidney. METHODS: Rats were infused with human parathyroid hormone (PTH, 15 microg kg(-1) day(-1)), or vehicle for 48 h using osmotic minipumps. RESULTS: The rats treated with PTH developed hypercalcaemia and exhibited metabolic alkalosis (arterial HCO: 31.1 +/- 0.8 vs. 28.1 +/- 0.8 mmol L(-1) in controls, P < 0.05, n = 6), whereas the urine pH of 6.85 +/- 0.1 was significantly decreased compared with the pH of 7.38 +/- 0.1 in controls (P < 0.05, n = 12). The observed alkalosis was associated with a significantly increased expression of the B1-subunit of the H(+)-ATPase in kidney inner medulla (IM, 233 +/- 45% of the control level). In contrast, electroneutral Na(+)-HCO cotransporter NBCn1 and Cl(-)/HCO anion exchanger AE2 expression was markedly reduced in the inner stripe of the outer medulla (to 26 +/- 9% and 65 +/- 6%, respectively). These findings were verified by immunohistochemistry. CONCLUSIONS: (1) hypercalcaemia-induced metabolic alkalosis was associated with increased urinary excretion of H(+); (2) the increased H(+)-ATPase expression in IM may partly explain the enhanced urinary acidification, which is speculated to prevent stone formation because of hypercalciuria and (3) the decreased expression of outer medullary AE2 suggests a compensatory reduction of the transepithelial bicarbonate transport.

Effect of high bicarbonate hemodialysis on ionized calcium and risk of metastatic calcification.

BACKGROUND: Disturbances in calcium and phosphate metabolism among chronic hemodialysis patients result in renal osteodystrophy and vascular calcification. Even though it is the ionized fraction of calcium that is metabolically active, this measurement is generally not available and decisions are made on the basis of total calcium. Formulae to predict ionized calcium concentrations are available. METHODS: The OPTI Critical Care Analyzer with E-Ca cuvettes was used on-site to measure acid-base parameters, electrolytes, and ionized calcium. Additional assays included total calcium, phosphate, and albumin. RESULTS: Using a dialysate with 1.25 or 1.5 mmol/l calcium and 40 mmol/l bicarbonate, we observed a statistically significant increase in pH and total CO2 concentrations in post-dialysis blood. Total and ionized calcium increased significantly only in the patients with central venous catheters but not in those with fistulas or grafts. All patients experienced a decrease in phosphate concentrations. CONCLUSIONS: The metabolic alkalosis induced by high bicarbonate dialysate was not associated with a decrease in ionized calcium or a change in the calculated concentration product ratio for hydroxyapatite formation in the immediate post-dialysis period. However, if a 40% phosphate rebound were to occur 2 h after termination of dialysis, the calculated risk of metastatic calcification would increase 2.8-fold compared to pre-dialysis conditions. Formulae to calculate ionized calcium are not useful in this population.