Assessment of Acute Kidney Injury in Neurologically Injured Patients Receiving Hypertonic Sodium Chloride: Does Chloride Load Matter?

Background: Increasing evidence suggests that large-volume infusions of 0.9% sodium chloride (NaCl) for resuscitation are associated with hyperchloremic metabolic acidosis, renal vasoconstriction, and increased risk of acute kidney injury (AKI). Patients with neurological injury may require hypertonic NaCl for therapeutic hypernatremia, treatment of cerebral salt wasting, hyponatremia, or elevated intracranial pressure. Consequently, this increased exposure to chloride may result in an increased risk for development of AKI. Objective: The primary aim of this study was to describe the risk for development of AKI in neurologically injured patients receiving large volumes of intravenous hypertonic NaCl. Methods: This single-center, retrospective study looked at neurologically injured patients who received hypertonic NaCl and sodium acetate. Data were collected to assess renal function, hyperchloremia, and acidemia. Receiver operating characteristic (ROC) curve analysis was used to determine the predictive association between the amount of daily and overall chloride exposure and development of AKI. Results: A total of 301 patients were screened, and of those, 142 were included. Of the 142 patients included, 13% developed AKI, and 38% developed hyperchloremia. Additionally, 32% of patients were switched from NaCl to sodium acetate after an average of 3.4 ± 1.5 days of NaCl therapy. The ROC curve demonstrated that if patients received greater than 2055 mEq of chloride over 7 days, they were more likely to develop AKI (sensitivity 72%, specificity 70%; P = 0.002; area under the curve = 0.7). Conclusion and Relevance: Neurologically injured patients receiving hypertonic sodium therapy with a high chloride load are at risk of developing hyperchloremia and AKI.

The Predictive Value of Salt Sensitivity and Osmotic Fragility in the Development of Cerebral Small Vessel Disease.

Increased salt intake in food probably affects the progression of cerebral small vessel disease (CSVD), which justifies the study of disturbances in sodium homeostasis associated with the development of CSVD. We aimed to clarify the role of salt sensitivity and osmotic fragility in the development of CSVD. Erythrocyte salt sensitivity was measured using the modified salt blood test, and osmotic fragility was measured using the classic osmotic fragility test in 73 patients with CSVD (48 women; 60.1 ± 6.5 years) and 19 healthy volunteers (14 women; 56.9 ± 6.4 years). Salt sensitivity and osmotic fragility exhibited a predictive value in relation to CSVD. These parameters were associated with an increase in white matter hyperintensities (P = 0.019 and 0.004, respectively). Their simultaneous use increased their predictive ability for CSVD (P < 0.000001; AUC (95% CI), 0.824 (0.724-0.923)). The possibility of predicting CSVD using erythrocyte salt sensitivity and osmotic fragility indicates the value of the individual glycocalyx buffer capacity in relation to sodium and the activity of sodium channels in the development of CSVD. Increased salt sensitivity and osmotic fragility seem to be risk factors for CSVD.

Hypopituitarism manifesting after invasive dental treatment in a patient with carcinoma of the tongue: a case report.

BACKGROUND: The symptoms of hypopituitarism are not usually discussed in the clinical setting of oral surgery. CASE PRESENTATION: We herein report a case of hypopituitarism that became evident after biopsy and extraction of several teeth in a 68-year-old man with tongue cancer. Three days after biopsy, the patient developed nausea and vomiting, and his serum sodium had fallen to 124 mEq/L. His serum cortisol concentration was low. Although the plasma concentration of adrenocorticotropic hormone (ACTH) was within the normal range, ACTH stimulation testing showed a lack of cortisol response. Given these findings, we suspected secondary adrenal insufficiency. To investigate the cause of secondary adrenal insufficiency, MRI of the head was performed, which revealed pituitary gland atrophy. The results of pituitary anterior lobe hormone-stimulation tests were compatible with hypopituitarism. Thirty days after biopsy, partial tongue resection was successfully performed under general anesthesia with perioperative hydrocortisone supplementation. CONCLUSIONS: We must be aware of various signs of hypopituitarism when we perform invasive dental treatment.

Association of Preoperative Serum Chloride Levels With Mortality and Morbidity After Noncardiac Surgery: A Retrospective Cohort Study.

BACKGROUND: Postoperative hyperchloremia is known to be related to increases in mortality and morbidity after surgery. However, the relationship between preoperative hyperchloremia and hypochloremia and postoperative mortality and morbidity is not well established. Our aim was to evaluate the relationship between preoperative hyperchloremia or hypochloremia, as assessed using preoperative serum chloride tests, and 90-day mortality and morbidity after noncardiac surgery. METHODS: In this retrospective cohort study, we reviewed the medical records of patients >20 years of age who underwent noncardiac surgery between January 2010 and December 2016. Patients were categorized into one of the following groups on the basis of the results of serum chloride testing performed within 1 month before surgery: normochloremia, 97-110 mmol·L; hyperchloremia, >110 mmol·L; and hypochloremia, <97 mmol·L. The primary end point of this study was the difference in postoperative 90-day mortality among the preoperative serum chloride groups. The secondary end point was the difference in postoperative acute kidney injury incidence among the preoperative serum chloride groups. RESULTS: A total of 106,505 patients were included in the final analysis (2147 were allocated to the preoperative hypochloremia group and 617 to the hyperchloremia group). Multivariable Cox regression analysis revealed significantly increased 90-day mortality in the hypochloremia (hazard ratio, 1.46; 95% CI, 1.16-1.84; P = .001) and hyperchloremia (hazard ratio, 1.76; 95% CI, 1.13-2.73; P = .013) groups when compared with the normochloremia group. In addition, multivariable logistic regression analysis revealed a 1.83-fold increased odds of acute kidney injury in the preoperative hypochloremia group when compared with the normochloremia group (odds ratio, 1.83; 95% CI, 1.53-2.19; P < .001). CONCLUSIONS: Preoperative hypochloremia and hyperchloremia were related to increased 90-day mortality after noncardiac surgery. In addition, preoperative hypochloremia was related to an increased risk for postoperative acute kidney injury.

Association between serum Na-Cl level and renal function decline in chronic kidney disease: results from the chronic kidney disease Japan cohort (CKD-JAC) study.

BACKGROUND: Metabolic acidosis, which reduces serum bicarbonate levels, contributes to the progression of chronic kidney disease (CKD). The difference between sodium and chloride (Na-Cl) may theoretically predict serum bicarbonate levels. This study aimed to evaluate serum Na-Cl level as a risk factor for renal function decline among patients who participated in the chronic kidney disease Japan cohort (CKD-JAC) study. METHODS: The association between low Na-Cl concentration (< 34 mmol/L) and composite renal function decline events (any initiation of renal replacement therapy or 50% decline in estimated glomerular filtration rate) was evaluated among 2143 patients with CKD stage G3a-4. Using Cox regression analysis, hazard ratios (HRs) were estimated after adjusting for the following covariates: age, sex, diabetes mellitus, diabetic nephropathy, cardiovascular disease, anemia, angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, loop diuretics, cigarette smoking, body mass index, serum albumin, systolic blood pressure, urine albumin-to-creatinine ratio, and CKD stage. RESULTS: Composite renal function decline events were observed in 405 patients (18.9%) over the 4-year follow-up period. Low serum Na-Cl level (< 34 mmol/L) was independently associated with a greater risk for composite renal function decline events (HR 1.384; 95% confidence interval [CI], 1.116-1.717). Subgroup analyses identified that the association between low Na-Cl level and composite renal function decline events was stronger among patients with CKD stage G4 and those with anemia. CONCLUSIONS: Our investigation suggests that Na-Cl is an independent predictor of CKD progression, especially among patients with CKD stage G4 and those with anemia.

A Controlled Increase in Dietary Phosphate Elevates BP in Healthy Human Subjects.

Background Despite epidemiologic evidence for increased cardiovascular morbidity and mortality associated with both high dietary and serum phosphate in humans with normal renal function, no controlled phosphate intervention studies of systemic hemodynamics have been reported. Higher serum 25(OH) vitamin D levels are associated with better cardiovascular outcomes, but vitamin D increases intestinal phosphate absorption.Methods We conducted a prospective outpatient study with blinded assessment in 20 young adults with normal renal function randomized to high phosphate (regular diet plus 1 mmol/kg body wt per day of Na as neutral sodium phosphate) or low phosphate (regular diet plus lanthanum, 750 mg thrice/day, plus 0.7 mmol/kg body wt per day of Na as NaCl) for 11 weeks. After 6 weeks, all subjects received vitamin D3 (600,000 U) by intramuscular injection. Outcome parameters were 24-hour ambulatory systolic and diastolic BP (SBP and DBP), pulse rate (PR), biomarkers, and measures of endothelial and arterial function.Results Compared with the low-phosphate diet group, the high-phosphate diet group had a significant increase in mean±SEM fasting plasma phosphate concentration (0.23±0.11 mmol/L); 24-hour SBP and DBP (+4.1; 95% confidence interval [95% CI], 2.1 to 6.1; and +3.2; 95% CI, 1.2 to 5.2 mm Hg, respectively); mean 24-hour PR (+4.0; 95% CI, 2.0 to 6.0 beats/min); and urinary metanephrine and normetanephrine excretion (54; 95% CI, 50 to 70; and 122; 95% CI, 85 to 159 µg/24 hr, respectively). Vitamin D had no effect on any of these parameters. Neither high- nor low-phosphate diet nor vitamin D affected endothelial function or arterial elasticity.Conclusions Increased phosphate intake (controlled for sodium) significantly increases SBP, DBP, and PR in humans with normal renal function, in part, by increasing sympathoadrenergic activity.

Microfluidic Microwave Sensor for Detecting Saline in Biological Range.

A device for measuring biological small volume liquid samples in real time is appealing. One way to achieve this is by using a microwave sensor based on reflection measurement. A prototype sensor was manufactured from low cost printed circuit board (PCB) combined with a microfluidic channel made of polymethylsiloxane (PDMS). Such a sensor was simulated, manufactured, and tested including a vacuum powered sample delivery system with robust fluidic ports. The sensor had a broad frequency band from 150 kHz to 6 GHz with three resonance frequencies applied in sensing. As a proof of concept, the sensor was able to detect a NaCl content of 125 to 155 mmol in water, which is the typical concentration in healthy human blood plasma.

Hyperchloremia and postoperative acute kidney injury: a retrospective analysis of data from the surgical intensive care unit.

BACKGROUND: Whether perioperative hyperchloremia can induce postoperative acute kidney injury (AKI) is controversial. We investigated the association between perioperative hyperchloremia and postoperative AKI in patients admitted to the intensive care unit (ICU) after surgery. METHODS: We performed a retrospective observational study of patients admitted to the surgical ICU at a single tertiary care hospital between January 2011 and June 2016. Our primary objective was to determine whether hyperchloremia or an increase in serum chloride levels was associated with postoperative AKI. Perioperative hyperchloremia was defined as serum chloride levels ≥ 110 mmol·L- 1 during postoperative days (PODs) 0-3. The increase in serum chloride levels was defined as the difference between preoperative and maximum postoperative serum chloride levels during the first 3 days after surgery. RESULTS: Of the 7991 patients included in the final analysis, 1876 (23.5%) developed hyperchloremia during PODs 0-3, and 1187 (14.9%) developed postoperative AKI. Exposure to hyperchloremia during the first 3 days after surgery was not associated with postoperative AKI (odds ratio, 1.09; 95% confidence interval, 0.80-1.49; P = 0.571). However, among patients with preoperative chronic kidney disease stage ≥ 3 (estimated glomerular filtration rate < 60 mL·min- 1·1.73·m- 2), the incidence of postoperative AKI was higher in patients with an increase > 6 mmol·L- 1 in serum chloride levels than in patients with an increase ≤ 1 mmol·L- 1 (odds ratio, 1.42; 95% confidence interval, 1.09-1.84; P = 0.009). In addition, the incidence of postoperative AKI stage ≥ 2 was not associated with exposure to hyperchloremia or with the increase in serum chloride levels during PODs 0-3, regardless of preoperative kidney function. CONCLUSIONS: Exposure to perioperative hyperchloremia is not associated with postoperative AKI in surgical ICU patients. However, in patients with moderate-to-severe chronic kidney disease (stage ≥ 3), a substantial perioperative increase in serum chloride levels may reflect a higher risk of AKI.

Role of Vasopressin in Rat Models of Salt-Dependent Hypertension.

PURPOSE OF REVIEW: Dietary salt intake increases both plasma sodium and osmolality and therefore increases vasopressin (VP) release from the neurohypophysis. Although this effect could increase blood pressure by inducing fluid reabsorption and vasoconstriction, acute activation of arterial baroreceptors inhibits VP neurons via GABAA receptors to oppose high blood pressure. Here we review recent findings demonstrating that this protective mechanism fails during chronic high salt intake in rats. RECENT FINDINGS: Two recent studies showed that chronic high sodium intake causes an increase in intracellular chloride concentration in VP neurons. This effect causes GABAA receptors to become excitatory and leads to the emergence of VP-dependent hypertension. One study showed that the increase in intracellular chloride was provoked by a decrease in the expression of the chloride exporter KCC2 mediated by local secretion of brain-derived neurotrophic factor and activation of TrkB receptors. Prolonged high dietary salt intake can cause pathological plasticity in a central homeostatic circuit that controls VP secretion and thereby contribute to peripheral vasoconstriction and hypertension.

Evaluation of Amount of Blood in Dry Blood Spots: Ring-Disk Electrode Conductometry.

A fixed area punch in dried blood spot (DBS) analysis is assumed to contain a fixed amount of blood, but the amount actually depends on a number of factors. The presently preferred approach is to normalize the measurement with respect to the sodium level, measured by atomic spectrometry. Instead of sodium levels, we propose electrical conductivity of the extract as an equivalent nondestructive measure. A dip-type small diameter ring-disk electrode (RDE) is ideal for very small volumes. However, the conductance (G) measured by an RDE depends on the depth (D) of the liquid below the probe. There is no established way of computing the specific conductance (σ) of the solution from G. Using a COMSOL Multiphysics model, we were able to obtain excellent agreement between the measured and the model predicted conductance as a function of D. Using simulations over a large range of dimensions, we provide a spreadsheet-based calculator where the RDE dimensions are the input parameters and the procedure determines the 99% of the infinite depth conductance (G99) and the depth D99 at which this is reached. For typical small diameter probes (outer electrode diameter ∼ <2 mm), D99 is small enough for dip-type measurements in extract volumes of ∼100 µL. We demonstrate the use of such probes with DBS extracts. In a small group of 12 volunteers (age 20-66), the specific conductance of 100 µL aqueous extracts of 2 µL of spotted blood showed a variance of 17.9%. For a given subject, methanol extracts of DBS spots nominally containing 8 and 4 µL of blood differed by a factor of 1.8-1.9 in the chromatographically determined values of sulfate and chloride (a minor and major constituent, respectively). The values normalized with respect to the conductance of the extracts differed by ∼1%. For serum associated analytes, normalization of the analyte value by the extract conductance can thus greatly reduce errors from variations in the spotted blood volume/unit area.

Hyperchloremia and moderate increase in serum chloride are associated with acute kidney injury in severe sepsis and septic shock patients.

BACKGROUND: Acute kidney injury and hyperchloremia are commonly present in critically ill septic patients. Our study goal was to evaluate the association of hyperchloremia and acute kidney injury in severe sepsis and septic shock patients. METHODS: In this retrospective cohort study in a provincial tertiary care hospital, adult patients with severe sepsis or septic shock and serum chloride measurements were included. Serum chloride was measured on a daily basis for 48 hours. Primary outcome was development of acute kidney injury (AKI) and association of AKI and serum chloride parameters was analyzed. RESULTS: A total of 240 patients were included in the study, 98 patients (40.8 %) had hyperchloremia. The incidence of acute kidney injury (AKI) was significantly higher in the hyperchloremia group (85.7 % vs 47.9 %; p < 0.001). Maximal chloride concentration in the first 48 hours ([Cl-]max) was significantly associated with AKI. In multivariate analysis, [Cl-]max was independently associated with AKI [adjusted odds ratio (OR) for AKI = 1.28 (1.02-1.62); p = 0.037]. The increase in serum chloride (Δ[Cl-] = [Cl-]max - initial chloride concentration) demonstrated a dose-dependent relationship with severity of AKI. The mean Δ[Cl-] in patients without AKI was 2.1 mmol/L while in the patients with AKI stage 1, 2 and 3 the mean Δ[Cl-] was 5.1, 5.9 and 6.7 mmol/L, respectively. A moderate increase in serum chloride (Δ[Cl-] ≥ 5 mmol/L) was associated with AKI [OR = 5.70 (3.00-10.82); p < 0.001], even in patients without hyperchloremia [OR = 8.25 (3.44-19.78); p < 0.001]. CONCLUSIONS: Hyperchloremia is common in severe sepsis and septic shock and independently associated with AKI. A moderate increase in serum chloride (Δ[Cl-] ≥5 mmol/L) is associated with AKI even in patients without hyperchloremia.

Thermoregulatory consequences of salt loading in the lizard Pogona vitticeps.

Previous research has demonstrated that dehydration increases the threshold temperature for panting and decreases the thermal preference of lizards. Conversely, it is unknown whether thermoregulatory responses such as shuttling and gaping are similarly influenced. Shuttling, as an active behavioural response, is considered one of the most effective thermoregulatory behaviours, whereas gaping has been proposed to be involved in preventing brain over-heating in lizards. In this study we examined the effect of salt loading, a proxy for increased plasma osmolality, on shuttling and gaping in Pogona vitticeps. Then, we determined the upper and lower escape ambient temperatures (UETa and LETa), the percentage of time spent gaping, the metabolic rate (V̇O2 ), the evaporative water loss (EWL) during gaping and non-gaping intervals and the evaporative effectiveness (EWL/V̇O2 ) of gaping. All experiments were performed under isotonic (154 mmol l(-1)) and hypertonic saline injections (625, 1250 or 2500 mmol l(-1)). Only the highest concentration of hypertonic saline altered the UETa and LETa, but this effect appeared to be the result of diminishing the animal's propensity to move, instead of any direct reduction in thermoregulatory set-points. Nevertheless, the percentage of time spent gaping was proportionally reduced according to the saline concentration; V̇O2 was also decreased after salt loading. Thermographic images revealed lower head than body surface temperatures during gaping; however this difference was inhibited after salt loading. Our data suggest that EWL/V̇O2 is raised during gaping, possibly contributing to an increase in heat transfer away from the lizard, and playing a role in head or brain cooling.

[STUDY OF THE EFFICACY OF REGULATION OF THE BLOOD SERUM PHYSICOCHEMICAL PARAMETERS IN CHILDREN WITH DYSFUNCTION OF PHYSIOLOGICAL SYSTEMS].

The physicochemical parameters of blood serum (osmolality, concentration of several ions, total protein, glucose) were studied in 200 children of different age with various forms of pathology. The variability of each parameter was calculated. A high level of stability of the parameters studies was revealed in healthy children and in children with dysfunction of various systems (disease of the respiratory system, gastrointestinal tract, renal and urinary tract, nervous and endocrine systems). However, estimation of their coefficients of variation showed significant individual deviations of these parameters from the average value of the examined patients. This fact reflects the extent of efficacy of activity of different organs and regulatory systems under pathological processes. Combination of clinical and ontogenetic methods of evolutionary physiology in this study opens new possibilities for understanding the nature of regulation of water-salt balance in humans and points out to the expedience of using these approaches in the practical medicine.

0.9% saline induced hyperchloremic acidosis.

In the acute care setting, the type and amount of fluid administered has a significant impact on patient outcomes. In particular, 0.9% saline infusions are known to cause or exacerbate hyperchloremia. The studies presented evaluate possible complications from 0.9% saline infusions. These studies compared administration of 0.9% saline with lactated ringer or plasmalyte in the acute care setting. In each trial, the patients who were randomized to receive 0.9% saline infusions had a more severe acidosis from increased serum chloride levels. From the available data, chloride-restrictive intravenous fluid such as plasmalyte appears to reduce acid-base disturbances and improve patient outcomes.

A novel balanced isotonic sodium solution vs normal saline during major surgery in children up to 36 months: a multicenter RCT.

BACKGROUND: The use of isotonic electrolytic solutions for the intraoperative fluid management in children is largely recognized, but the exact composition still needs to be defined. OBJECTIVES: The primary objective of this randomized controlled open trial was to compare the changes in chloride plasma concentration using two intraoperative isotonic fluid regimens (Sterofundin vs. normal saline, both added with 1% of glucose) in children undergoing major surgery. Secondary objectives were to compare changes in other electrolytes, renal function, and the occurrence of hypoglycemia. METHODS: Children aged between 1 and 36 months, scheduled for major surgery, were randomized to receive Sterofundin or saline during the intraoperative time. Children with preoperative electrolyte abnormalities, hemodynamic instability, and severe renal or hepatic dysfunction were excluded. The primary outcome was the Δ of Cl(-) (Δ = change in plasma concentration between post- and pre-infusion), and secondary outcomes included Δ of other electrolytes and intraoperative hypoglycemia. RESULTS: A total of 240 patients were included in the two study sites and randomized to receive Sterofundin plus 1% glucose or normal saline plus 1% glucose, in a open fashion (229 were finally analyzed). Δ of Cl- and Mg++ was statistically less relevant in patients who received intraoperative Sterofundin, and Δ of the other electrolytes was comparable between the two study groups. Relative risk of hyperchloremia was significantly higher when large volumes were infused (over than 46.7 ml·kg(-1) ), regardless of type of crystalloid infused. Hypoglycemia occurred in two of 229 patients. CONCLUSIONS: Sterofundin is safer than normal saline in protecting young children undergoing major surgery against the risk of increasing plasma chlorides and the subsequent metabolic acidosis.

[Clinical significance of serum and urinary biomarkers for water-salt metabolism in patients with proteinuric forms of chronic glomerulonephritis].

AIM: To determine the nature and magnitude of changes in the detectable serum and urinary biomarkers of water-salt metabolism in patients with proteinuric forms of chronic glomerulonephritis (CGN), their importance for assessing the activity and prognosis of the disease. SUBJECTS AND METHODS: Forty-seven patients with CGN were examined. Group 1 included 10 patients with nephrotic syndrome (NS) and decreased renal function; Group 2 comprised 16 patients with persistent NS and normal renal function; Group 3 consisted of 10 patients with partial remission of NS; Group 4 included 11 patients with active hematuric CGN. A control group consisted of 9 healthy individuals matched for gender and age with the patients with CGN. The serum level of copeptin and the urinary excretion of aquaporine-2 (AQP-2) and kidney injury molecule-1 (KIM-1) were determined by indirect enzyme-linked immunosorbent assay (ELISA). RESULTS: In the NS patients with and without renal dysfunction, the serum copeptin concentration was significantly higher than that in those with partial remission of NS or hematuric CGN and in the controls. In the patients with hematuric CGN, this indicator was virtually different from that in the control group. Urinary AQP-2 excretion was significantly similar in 3 NS groups. In the patients with hematuric CGN, the urinary AQP-2 concentration was higher than that in those with NS, but it was significantly lower than in the control group. The highest urinary excretion of KIM-1 was found in the patients with NS and diminished renal function while its excretion was significantly lower in the patients with NS and stable renal function, as in those with partial remission of NS. The lowest values were seen in the patients with hematuric CGN and in the control group; the differences between these groups were statistically insignificant. Correlation analysis showed that there was an inverse correlation between serum copeptin and urinary AQP-2 levels and between urinary AQP- 2 and KIM-1 levels. CONCLUSION: Serum copeptin levels and urinary AQP-2 secretion may be used to assess the activity of CGN and NS and to evaluate therapeutic effectiveness. The determination of urinary KIM-1 excretion may be of the same practical value in patients with NS. It has been shown that the concentrations of copeptin, APQ-2, and KIM-1 may be used as a differential diagnostic criterion for hematuric CGN.

Effects of atorvastatin on systemic and renal nitric oxide in healthy man.

Statin treatment improves endothelial function but the effects of statins on renal nitric oxide have not been clarified. In this crossover study, 26 healthy subjects received atorvastatin 80 mg per day or placebo for 5 days. After 5 days of treatment, L-N(G)-monomethyl arginine caused a similar increase in blood pressure and decrease in urine output and glomerular filtration rate. The decrease in fractional excretion of sodium to L-N(G)-monomethyl arginine was more pronounced after atorvastatin treatment. Atorvastatin did not change the response to several vasoactive hormones. The results indicate that atorvastatin increase renal nitric oxide, which may explain a part of the pleiotropic effects of statins.

[Some clinical aspects of sodium homeostasis disorders]. / A nátriumháztartás zavarainak néhány klinikai vonatkozása.

In this review three major issues of sodium homeostasis are addressed. Specifically, volume-dependent (salt-sensitive) hypertension, sodium chloride content of maintenance fluid and clinical evaluation of hyponatremia are discussed. Regarding volume-dependent hypertension the endocrine/paracrine systems mediating renal sodium retention, the relationship between salt intake, plasma sodium levels and blood pressure, as well as data on the dissociation of sodium and volume regulation are presented. The concept of perinatal programming of salt-preference is also mentioned. Some theoretical and practical aspects of fluid therapy are summarized with particular reference to using hypotonic sodium chloride solution for maintenance fluid as opposed to the currently proposed isotonic sodium chloride solution. Furthermore, the incidence, the aetiological classification and central nervous system complications of hyponatremia are presented, too. In addition, clinical and pathophysical features of hyponatremic encephalophathy and osmotic demyelinisation are given. The adaptive reactions of the brain to hypotonic stress are also described with particular emphasis on the role of brain-specific water channel proteins (aquaporin-4) and the benzamil-inhibitable sodium channels. In view of the outmost clinical significance of hyponatremia, the principles of efficient and safe therapeutic approaches are outlined.

A physiological concept unmasking vascular salt sensitivity in man.

About one third of the population worldwide is supposed to be salt sensitive which is a major cause for arterial hypertension later in life. For preventive actions it is thus desirable to identify salt-sensitive individuals before the appearance of clinical symptoms. Recent observations suggest that the vascular endothelium consists of two salt-sensitive barriers in series, the glycocalyx that buffers sodium and the endothelial cell membrane that contains sodium channels. Glycocalyx sodium buffer capacity and sodium channel activity are conversely related to each other. For proof of concept, a so-called salt provocation test (SPT) was developed that should unmask vascular salt sensitivity in humans at virtually any age. Nineteen healthy subjects, ranging from 25 to 63 years of age, underwent two series of 1-h blood pressure measurements after acute ingestion of a salt cocktail with or without addition of a sodium channel blocker effective in vascular endothelium. Differential analysis of the changes in diastolic blood pressure (net ∆DP) identified 12 individuals (63%) as being salt resistant (net ∆DP = -0.05 ± 0.62 mmHg) and seven individuals (37%) as being salt sensitive (net ∆DP = +6.98 ± 0.75 mmHg). Vascular salt sensitivity was not related to the age of the study participants. It is concluded that the SPT could be useful for identifying vascular salt sensitivity in humans already early in life.