Sodium Loading Research Articles

Genetic Variance in Heparan Sulfation Is Associated With Salt Sensitivity.

High heritability of salt sensitivity suggests an essential role for genetics in the relationship between sodium intake and blood pressure (BP). The role of glycosaminoglycan genes, which are crucial for salinity tolerance, remains to be elucidated. Interactions between 54 126 variants in 130 glycosaminoglycan genes and daily sodium excretion on BP were explored in 20 420 EPIC-Norfolk (European Prospective Investigation Into Cancer in Norfolk) subjects. The UK Biobank (n=414 132) and the multiethnic HELIUS study (Healthy Life in an Urban Setting; n=2239) were used for validation. Afterward, the urinary glycosaminoglycan composition was studied in HELIUS participants (n=57) stratified by genotype and upon dietary sodium loading in a time-controlled crossover intervention study (n=12). rs2892799 in NDST3 (heparan sulfate N-deacetylase/N-sulfotransferase 3) showed the strongest interaction with sodium on mean arterial pressure (false discovery rate 0.03), with higher mean arterial pressure for the C allele in high sodium conditions. Also, rs9654628 in HS3ST5 (heparan sulfate-glucosamine 3-sulfotransferase 5) showed an interaction with sodium on systolic BP (false discovery rate 0.03). These interactions were multiethnically validated. Stratifying for the rs2892799 genotype showed higher urinary expression of N-sulfated heparan sulfate epitope D0S0 for the T allele. Conversely, upon dietary sodium loading, urinary D0S0 expression was higher in participants with stable BP after sodium loading, and sodium-induced effects on this epitope were opposite in individuals with and without BP response to sodium. The C allele of rs2892799 in NDST3 exhibits higher BP in high sodium conditions when compared with low sodium conditions, whereas no differences were detected for the T allele. Concomitantly, both alleles demonstrate distinct expressions of D0S0, which, in turn, correlates with sodium-mediated BP elevation. These findings underscore the potential significance of genetic glycosaminoglycan variation in human BP regulation.

Abstract 72: Genetic variance in heparan sulfation is associated with salt-sensitivity: a gene-environment analysis in EPIC-Norfolk, UK biobank, and HELIUS

Background: High heritability of salt sensitivity suggests an essential role for genetics in the relationship between sodium intake and blood pressure (BP). The role of glycosaminoglycan (GAG) genes, which are crucial for salinity tolerance througout evolution, remains to be elucidated. Methods: Interactions between 54,126 variants in 130 GAG genes and daily sodium excretion on BP were explored in 20,420 EPIC-Norfolk subjects. UK Biobank (n=414,132) and the multi-ethnic HELIUS study (n=2,239, comprising a balanced representation of people from European, Subsaharan, South Asian, Turkish, and Moroccan descent) were used for validation. Afterwards, urinary GAG composition was studied in HELIUS participants (n=57) stratified by genotype, and upon dietary sodium loading in a time-controlled crossover intervention study (n=12). Results: rs2892799 (NDST3) showed the strongest interaction with sodium on mean arterial pressure (MAP) (FDR 0.03), with higher MAP for the C-allele in high sodium conditions. Also, rs9654628 (HS3ST5) showed an interaction with sodium on systolic BP (FDR 0.03). These interactions were multi-ethnically validated (figures A and B, respectively). Stratifying for rs2892799 genotype, showed higher urinary expression of N-sulfated heparan sulfate epitope D0S0 for the T-allele. Conversely, upon dietary sodium loading, urinary D0S0 expression was higher in participants with stable BP after sodium loading, and sodium-induced effects on this epitope were opposite in individuals with and without BP response to sodium. Conclusion: The C-allele of rs2892799 (NDST3) exhibits higher BP in high sodium conditions when compared to low sodium conditions, whereas no differences were detected for the T-allele. Concomitantly, both alleles demonstrate distinct expressions of D0S0, which, in turn, correlates with sodium-mediated BP elevation. These findings underscore the potential significance of genetic GAG variation in human BP regulation.

The influence of multi-step modification method on the adsorption effect of alkali metal adsorbent in high temperature corrosive environment

In order to mitigate the serious high-temperature corrosion problem caused by gaseous alkali metal salts on the heating surface of boilers, the adsorption effect of kaolinite for alkali metal vapor stood out among many silicon-aluminum-based adsorbents. To improve the adsorption capacity of kaolinite for alkali metal vapor, a novel multi-step modification method was proposed in this reported work. The multi-step modification method consisted of the following four steps, which were pre-intercalation, replacement intercalation, multiple intercalation, and exfoliation, and it was found that the multi-step modification method resulted in the increase of the particle size, the expansion of the interlayer spacing, and the expansion of the porosity structure of kaolinite. The physicochemical analyses showed that the multi-step modification method made it easier to dehydrate kaolinite to produce metakaolinite. In addition, it was found that the multi-step modification method led to the generation of a new crystalline phase of kaolinite, which was formed by the dehydration and condensation of methanol and AlOH groups. It also led to the pre-removal of some of the hydroxyl groups in kaolinite. The insoluble sodium loading capacity of the multi-step modified kaolinite was enhanced by 64.47% and the insoluble potassium loading capacity was enhanced by 29.68% under the adsorption condition of 850 °C for 45 min. Therefore, the multi-step modification method enhanced the alkali metal vapor adsorption capacity of raw kaolinite under high-temperature environment, which laid a certain foundation for subsequent research in this field.

An examination of the associations between nutritional peaking strategies in physique sport and competitor characteristics.

Physique athletes are subjectively judged on their on-stage esthetic per their competition division criteria. To succeed, competitors look to acutely enhance their appearance by manipulating nutritional variables in the days leading up to competition, commonly referred to as peak week (PW). Despite their documented wide adoption, PW strategies lack experimental evidence. Further, the relationship between the specific strategies and the characteristics of the competitors who implement them are unknown. The aim of this research was to examine the effect of competitor characteristics on the specific nutritional peaking strategies implemented, the length of these strategies, and the range of daily carbohydrate (CHO) intakes during these strategies. A 58-item survey was developed to gather information on peak week nutrition and training practices of physique athletes. A total of 160 respondents above the age of 18 who had competed in the last 5 years completed the nutrition section. The topics analyzed for this paper included competitor demographics, peaking strategies utilized, and PW CHO intakes. Competitor demographics are presented with the use of descriptive statistics. Associations between competitor demographics and peaking strategies implemented, peaking strategy length, and daily CHO intake ranges were assessed using multiple logistic regression, multiple ordinal logistic regression, and linear mixed models, respectively. From the sampled population, ages 24-39 years (71.2%), male (68.8%), natural (65%), and amateur (90%) were the most common characteristics from their respective categories, while mean competition preparation length was 20.35 ± 8.03 weeks (Males: 19.77 ± 7.56 weeks, Females: 21.62 ± 8.93 weeks), competition preparation body mass loss was 11.5 ± 5.56 kg (M: 12.7 ± 5.76 kg, F: 7.16 ± 3.99 kg), and competition body mass was 72.09 ± 15.74 kg (M: 80.15 ± 11.33 kg, F: 54.34 ± 7.16 kg). For males, the highest and lowest daily CHO intake during PW were 489.63 ± 224.03 g (6.22 ± 2.93 g/kg body mass) and 148.64 ± 152.01 g (1.94 ± 2.17 g/kg), respectively, while for females these values were 266.73 ± 131.23 g (5.06 ± 2.67 g/kg) and 94.42 ± 80.72 g (1.81 ± 1.57 g/kg), respectively. CHO back loading (45%) and water loading (40.6%) were the most popular peaking strategies, while the most prevalent peaking strategy length was 7 days (27.2%). None of the competitor characteristics predicted the use of CHO-based peaking strategies nor peaking strategy length. For non-CHO-based strategies, drug-enhanced competitors were more likely to restrict water than non-drug enhanced, while males and professional competitors had greater odds of loading sodium than females and amateurs, respectively. Finally, when comparing the disparity in highest and lowest CHO intakes during peak week, sex was the only significant factor. The results of this survey provide further information on the nutritional peaking strategies implemented by competitors. Certain characteristics were identified as predictors of sodium loading and water restriction, and the range of daily PW CHO intake. Contrastingly, no associations were found for CHO-based peaking strategies or peaking strategy length. While our analyses may be underpowered, and thus results should be interpreted with caution, it appears the nutritional peaking strategies implemented by physique competitors are seemingly complex and highly individual.

Comparison of four confirmatory tests for the diagnosis of primary aldosteronism: Bayesian analysis in the absence of a gold standard.

Captopril challenge test (CCT), seated saline infusion test (SSIT), oral sodium loading test (OSLT) and fludrocortisone suppression test (FST) are widely used diagnostic tests for primary aldosteronism (PA). These tests differ in terms of safety and complexity. Whether the simpler tests (CCT and SSIT) are comparable in diagnostic performance to the more complex ones (FST and OSLT) is unclear. To compare the diagnostic accuracy of the four tests. This is a retrospective study of hypertensive patients who were screened for PA and completed at least one confirmatory test. The patients were divided into two cohorts: one including those who completed one to three tests was used for the estimation of sensitivity and specificity. The other including those who completed four tests was used for the comparison of accuracy. Bayesian method was used to obtain the sensitivity, specificity, and Youden index of each test. The study included 1011 hypertensive patients. Among them, 895 patients completed one to three tests (including 889 CCT, 605 FST, 611 SSIT and 69 OSLT), and 116 patients completed four tests. SSIT had the highest sensitivity of 0.82(95% CI 0.78-0.86) but the lowest specificity of 0.76(0.70-0.80). OSLT had the lowest sensitivity of 0.65(0.56-0.75) but the highest specificity of 0.91(0.82-0.96). The sensitivity and specificity were 0.78 (95% CI, 0.75-0.82), 0.82 (95% CI, 0.78-0.85), for CCT, and 0.77 (95% CI, 0.73-0.81), 0.87 (95% CI, 0.82-0.91) for FST, respectively. The Youden index was not significantly different among the four tests[0.60(0.55-0.65) for CCT; 0.58(0.51-0.64) for SSIT; (0.64(0.57-0.69) for FST; 0.56(0.43-0.67) for OSLT]. The accuracy of simpler tests is comparable to the more complex ones. Considering the safety and simplicity of CCT, it may be a reasonable first choice when confirming the diagnosis of PA.

Integrated renal and sympathetic mechanisms underlying the development of sex- and age-dependent hypertension and the salt sensitivity of blood pressure

Aging is a non-modifiable understudied risk factor for hypertension. We hypothesized that sympathetically mediated activation of renal sodium reabsorption drives age-dependent hypertension and the salt sensitivity of blood pressure (BP). Using 3-, 8-, and 16-month-old male and female Sprague–Dawley rats as a model of normal aging, we assessed BP, indices of sympathetic tone, and the physiological responses to acute and chronic sodium challenge including sodium chloride cotransporter (NCC) regulation. The effects of renal nerve ablation and NCC antagonism were assessed in hypertensive male rats. We observed sex-dependent impaired renal sodium handling (24 h sodium balance (meq), male 3-month 0.36 ± 0.1 vs. 16-month 0.84 ± 0.2; sodium load excreted during 5% bodyweight isotonic saline volume expansion (%) male 3-month 77 ± 5 vs. 16-month 22 ± 8), hypertension (MAP (mmHg) male 3-month 123 ± 4 vs. 16-month 148 ± 6), and the salt sensitivity of BP in aged male, but not female, rats. Attenuated sympathoinhibitory afferent renal nerve (ARN) responses contributed to increased sympathetic tone and hypertension in male rats. Increased sympathetic tone contributes to renal sodium retention, in part through increased NCC activity via a dysfunctional with-no-lysine kinase-(WNK) STE20/SPS1-related proline/alanine-rich kinase signaling pathway, to drive hypertension and the salt sensitivity of BP in aged male rats. NCC antagonism and renal nerve ablation, which reduced WNK dysfunction and decreased NCC activity, attenuated age-dependent hypertension in male Sprague–Dawley rats. The contribution of an impaired sympathoinhibitory ARN reflex to sex- and age-dependent hypertension in an NCC-dependent manner, via an impaired WNK1/WNK4 dynamic, suggests this pathway as a mechanism-based target for the treatment of age-dependent hypertension.

Actual electrolyte intake during the first week of life and morbidity in very-low-birthweight infants.

To describe sodium and potassium intake, their sources and plasma concentrations, and the association between intake and morbidity in very-low-birthweight (VLBW, <1500 g) infants during the first week of life. This retrospective cohort study comprised 951 VLBW infants born at <32 weeks. Infants were divided into three groups according to gestational age: 23-26 (n = 275), 27-29 (n = 433) and 30-31 (n = 243) weeks. Data on fluid management and laboratory findings were acquired from an electronic patient information system. The median sodium intake was highest in the 23-26 week group, peaking at 6.4 mmol/kg/day. A significant proportion of sodium derived from intravascular flushes; it reached 27% on day 1 in the 23-26 week group. High cumulative sodium intake in the first postnatal week was associated with weight gain from birth to day 8 in the 23-26 week group. High intake of sodium associated with an increased risk of surgically ligated patent ductus arteriosus (PDA), bronchopulmonary dysplasia and intraventricular haemorrhage, whereas low intake of potassium associated with an increased risk of PDA. Sodium intake in the most premature infants exceeded recommendations during the first postnatal week. Saline flushes accounted for a significant proportion of the sodium load.

A study on the early metabolic effects of salt and fructose consumption: the protective role of water

Increasing serum osmolality has recently been linked with acute stress responses, which over time can lead to increased risk for obesity, hypertension, and other chronic diseases. Salt and fructose are two major stimuli that can induce acute changes in serum osmolality. Here we investigate the early metabolic effects of sodium and fructose consumption and determine whether the effects of sodium or fructose loading can be mitigated by blocking the change in osmolality with hydration. Forty-four healthy subjects without disease and medication were recruited into four groups. After overnight fasting, subjects in Group 1 drank 500 mL of salty soup, while those in Group 2 drank 500 mL of soup without salt for 15 min. Subjects in Group 3 drank 500 mL of 100% apple juice in 5 min, while subjects in Group 4 drank 500 mL of 100% apple juice and 500 mL of water in 5 min. Blood pressure (BP), plasma sodium, and glucose levels were measured every 15 min in the first 2 h. Serum and urine osmolarity, serum uric acid, cortisol, fibroblast growth factor 21 (FGF21), aldosterone, adrenocorticotropic hormone (ACTH) level, and plasma renin activity (PRA) were measured at the baseline and 2 h. Both acute intake of salt or fructose increased serum osmolality (maximum ∼4 mOsm/L peaking at 75 min) associated with a rise in systolic and diastolic BP, PRA, aldosterone, ACTH, cortisol, plasma glucose, uric acid, and FGF21. Salt tended to cause greater activation of the renin-angiotensin-system (RAS), while fructose caused a greater rise in glucose and FGF21. In both cases, hydration could prevent the osmolality and largely block the acute stress response. Acute changes in serum osmolality can induce remarkable activation of the ACTH-cortisol, RAS, glucose metabolism, and uric acid axis that is responsive to hydration. In addition to classic dehydration, salt, and fructose-containing sugars can activate these responses. Staying well hydrated may provide benefits despite exposure to sugar and salt. More studies are needed to investigate whether hydration can block the chronic effects of sugar and salt on disease.

Sodium Loading Does Not Induce Oxidative Stress-Mediated Reductions in Vascular Function in Young Adults

Short-term, high sodium diets decrease dilation responses in conduit arteries and the microvasculature when compared to low sodium diets (e.g., 7000 vs. 500 mg/day). Supraphysiological antioxidant treatment mitigates these effects supporting a role for oxidative stress in sodium-induced vascular impairments. It is unclear whether these effects are present when high sodium conditions are compared to the sodium level of a typical American diet (~3400 mg/day). Therefore, we tested the hypotheses that sodium added to the habitual diet of young adults would reduce flow mediated dilation (FMD) and post-ischemic reactive hyperemia (RH) and that an acute infusion of the antioxidant ascorbic acid (AA) would attenuate the vascular consequences of excess sodium. Methods: Young adults (6M / 8F; age: 26 ± 4 y; BMI: 23.6 ± 2.5 kg/m2) were studied following 10 days of sodium loading (SL) via table salt-filled capsules (3900 mg sodium/day) and 10 days of placebo capsules in addition to their normal diet, in random order. Total sodium intake was estimated via 24-hour urinary sodium content on day 10. On day 11, brachial artery diameter and blood velocity were continuously measured via duplex ultrasound at baseline and after 5 min of forearm ischemia. FMD, the post-ischemic change in brachial artery diameter relative to baseline diameter, provided an index of conduit artery endothelial function. The total RH in the 2 min following ischemia was measured for an index of microvascular function. Within each condition, testing was performed before (pre-AA) and after (post-AA) a 20 min intravenous infusion of 0.06 g of AA/kg lean body mass. Results: Urinary sodium content was increased by SL compared to the placebo (285 ± 94 vs. 160 ± 75 mmol/24 h, p&lt;0.001) indicating approximate sodium intakes of 6600 and 3700 mg/day, respectively. Mean arterial pressure did not differ across conditions pre-AA (SL: 77 ± 7; placebo: 75 ± 5 mmHg, P=0.40) or post-AA (SL: 79 ± 8; placebo: 76 ± 5 mmHg, P=0.17). Brachial artery FMD was not different across time or condition (SL pre-AA: 8.7 ± 3.6, post-AA: 8.8 ± 4.2% vs. placebo pre-AA: 8.8 ± 3.2, post-AA: 8.1 ± 3.5%, time x condition interaction P=0.48). RH was similar following SL and placebo (condition effect: P=0.38) but was reduced in both conditions post AA (SL: Δ-45 ± 44 ml, P=0.01; placebo: Δ-72 ± 59ml, p&lt;0.001). Conclusion: Contrary to our hypothesis, 10 days of sodium loading did not decrease FMD or post- ischemic RH in young adults compared to their habitual diet. Likewise, acute antioxidant treatment did not augment FMD in either condition and paradoxically decreased total RH independent of sodium intake. These data suggest that a short-term increase in dietary sodium intake in healthy young adults does not elicit oxidative stress-induced reductions in vascular function. NIH 5R01HL104106 and 5P20GM113125; AHA 20POST35080171. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

ACUTE EFFECTS OF SODIUM CHLORIDE OR ITS SUBSTITUTE POTASSIUM CHLORIDE ON VASCULAR FUNCTION IN HEALTHY VOLUNTEERS

Objective: High blood pressure, one of the most important risk factors for cardiovascular mortality, leads to vascular dysfunction and subsequently to arteriosclerosis, stroke, kidney and heart failure. High salt intake and low potassium intake are associated with high blood pressure and an increased risk of cardiovascular disease and mortality. Partial replacement of sodium with potassium led to a lower risk of cardiovascular events and death in a long-term follow-up study. However, the exact mechanism remains unclear. Our aim was to investigate the acute effects of sodium or potassium intake on vascular health to unravel the underlying mechanisms leading to vascular adaptations. Design and method: Six male and nine female healthy individuals (mean age 31 years) were randomized to either 9g of sodium chloride (high salt group), 6g of sodium chloride (regular salt group) or 6 g of sodium chloride plus 3g of potassium chloride group (substitution group). Individuals received a salty soup with the corresponding sodium or potassium load. Blood analyses, blood pressure, body composition and macro- as well as microvascular measurements were performed before as well as four (t4) and 24 hours (t24) after soup intake. To investigate macrovascular health, carotid-to-femoral pulse wave velocity was analyzed. Microvascular health was measured by investigating retinal vessel diameters. Results: The high (139±2mmol/l vs. 143±2mmol/l p=0,003) and regular salt group (140±2mmol/l vs. 141±0,6 mmol/l p=0,029) showed both higher serum sodium concentrations at t4 compared to baseline. These higher values were normalized at t24. The serum sodium concentration of the substitution group showed no statistically significant difference between timepoints. The substitution group showed improved microvascular health, quantified by higher arteriolar-to-venular diameter ratio from baseline to t4 (0,86±0,09 vs. 0,89±0,08 p=0,005). These improvements were regressive at t24 (0,88±0,09). No statistically significant changes were found on pulse wave velocity. The high and regular salt group showed no statistically significant differences at any timepoint on micro- or macrovascular health parameters. Conclusions: Replacement of sodium by potassium seems to improve microvascular function directly after potassium intake. These results might explain the long-term beneficial effects of potassium on cardiovascular outcomes.

The effect of different dialysate sodium concentrations on ambulatory blood pressure in hemodialysis patients: a prospective interventional study.

Hypertension is associated with increased morbidity and mortality in hemodialysis patients. Existing recommendations suggest reduction of sodium load, but the effect of dialysate sodium on blood pressure (BP) is not fully elucidated. The aim of the present study is to investigate the effect of different dialysate sodium concentrations on 72-h ambulatory BP in hemodialysis patients. This prospective study included patients on standard thrice-weekly hemodialysis. All patients initially underwent six sessions with dialysate sodium concentration of 137meq/L, followed consecutively by another six sessions with dialysate sodium of 139meq/L and, finally, six sessions with dialysate sodium of 141meq/L. At the start of the sixth hemodialysis session on each sodium concentration, 72-h ABPM was performed over the long interdialytic interval to evaluate ambulatory systolic and diastolic BP (SBP and DBP) during the overall 72-h, different 24-h, daytime and night-time periods. Twenty-five patients were included in the final analysis. A significant increase in the mean 72-h SBP was observed with higher dialysate sodium concentrations (124.8±16.6mmHg with 137meq/L vs 126.3±17.5mmHg with 139meq/L vs 132.3±19.31mmHg with 141meq/L, P=0.002). Similar differences were noted for DBP; 72-h DBP was significantly higher with increasing dialysate sodium concentrations (75.1±11.3mmHg with 137meq/L vs 76.3±13.7mmHg with 139meq/L vs 79.5±13.9mmHg with 141meq/L dialysate sodium, P=0.01). Ambulatory BP during the different 24-h intervals, daytime and night-time periods was also progressively increasing with increasing dialysate sodium concentration. This pilot study showed a progressive increase in ambulatory BP with higher dialysate sodium concentrations. These findings support that lower dialysate sodium concentration may help towards better BP control in hemodialysis patients.

NaHCO3 loading causes increased arterial pressure and kidney damage in rats with chronic kidney disease.

Sodium bicarbonate (NaHCO3) is commonly utilized as a therapeutic to treat metabolic acidosis in people with chronic kidney disease (CKD). While increased dietary sodium chloride (NaCl) is known to promote volume retention and increase blood pressure, the effects of NaHCO3 loading on blood pressure and volume retention in CKD remain unclear. In the present study, we compared the effects of NaCl and NaHCO3 loading on volume retention, blood pressure, and kidney injury in both 2/3 and 5/6 nephrectomy remnant kidney rats, a well-established rodent model of CKD. We tested the hypothesis that NaCl loading promotes greater volume retention and increases in blood pressure than equimolar NaHCO3. Blood pressure was measured 24 h daily using radio telemetry. NaCl and NaHCO3 were administered in drinking water ad libitum or infused via indwelling catheters. Rats were housed in metabolic cages to determine volume retention. Our data indicate that both NaHCO3 and NaCl promote hypertension and volume retention in remnant kidney rats, with salt-sensitivity increasing with greater renal mass reduction. Importantly, while NaHCO3 intake was less pro-hypertensive than equimolar NaCl intake, NaHCO3 was not benign. NaHCO3 loading significantly elevated blood pressure and promoted volume retention in rats with CKD when compared with control rats receiving tap water. Our findings provide important insight into the effects of sodium loading with NaHCO3 in CKD and indicate that NaHCO3 loading in patients with CKD is unlikely to be benign.

Why should we use a low sodium dialysis solution for peritoneal dialysis?

Overhydration is highly prevalent in patients on peritoneal dialysis (PD), with inappropriately high sodium load supposedly playing a central role in the pathophysiology of the conditions. Recent studies have revealed the novel role of the interstitium as a buffer system for sodium ions, and it has been reported that patients on dialysis, including PD, present increased levels of sodium in the interstitium, such as in subcutaneous tissue and muscle. Hence, therapy for correction of overhydration should target the excess extracellular volume and the excess sodium storage in the interstitium. The ultrafiltrate obtained using the currently available PD solutions is hypo- to isonatric as compared to serum, which is disadvantageous for prompt and efficient sodium removal from the body in patients with overhydration. In contrast, use of low sodium PD solutions is characterised by iso- to hypernatric ultrafiltrate, which may beneficial for reducing sodium storage in the interstitium. Trials of low sodium PD solutions have reported possible clinical merits, for example, decreased blood pressure, reduced dryness of mouth and decreased body water content as assessed using bioimpedance methods. Given these observations and the high prevalence of overhydration in current PD populations, it makes medical sense that low sodium solutions be positioned as the new standard solution in the future. However, for medical safety, that is, to avoid hyponatremia and excessive decreases in blood pressure, further studies are needed to establish the appropriate compositions and applications of low sodium solutions.

Sodium loading in ambulatory patients with heart failure with reduced ejection fraction: Mechanistic insights into sodium handling.

Sodium restriction was not associated with improved outcomes in heart failure patients in recent trials. The skin might act as a sodium buffer, potentially explaining tolerance to fluctuations in sodium intake without volume overload, but this is insufficiently understood. Therefore, we studied the handling of an increased sodium load in patients with heart failure with reduced ejection fraction (HFrEF). Twenty-one ambulatory, stable HFrEF patients and 10 healthy controls underwent a 2-week run-in phase, followed by a 4-week period of daily 1.2 g (51 mmol) sodium intake increment. Clinical, echocardiographic, 24-h urine collection, and bioelectrical impedance data were collected every 2 weeks. Blood volume, skin sodium content, and skin glycosaminoglycan content were assessed before and after sodium loading. Sodium loading did not significantly affect weight, blood pressure, congestion score, N-terminal pro-brain natriuretic peptide, echocardiographic indices of congestion, or total body water in HFrEF (all p > 0.09). There was no change in total blood volume (4748 ml vs. 4885 ml; p = 0.327). Natriuresis increased from 150 mmol/24 h to 173 mmol/24 h (p = 0.024), while plasma renin decreased from 286 to 88 μU/L (p = 0.002). There were no significant changes in skin sodium content, total glycosaminoglycan content, or sulfated glycosaminoglycan content (all p > 0.265). Healthy controls had no change in volume status, but a higher increase in natriuresis without any change in renin. Selected HFrEF patients can tolerate sodium loading, with increased renal sodium excretion and decreased neurohormonal activation.

Postoperative fluid therapy in enhanced recovery after surgery for pancreaticoduodenectomy.

Optimal intravenous fluid management during the perioperative period for patients undergoing pancreaticoduodenectomy (PD) within the framework of enhanced recovery after surgery (ERAS) is unclear. Studies have indicated that excessive total body salt and water can contribute to the development of oedema, leading to increased morbidity and extended hospital stays. This study aimed to assess the effects of an intravenous therapy regimen during postoperative day (POD) 0 to 2 in PD patients within ERAS. A retrospective interventional cohort study was conducted, and it involved all PD patients before and after implementation of ERAS (2009-2017). In the ERAS group, a targeted maintenance fluid regimen of 20 mL/kg/day with a sodium requirement of 0.5 mmoL/kg/day was administered. Outcome measures included the mmol of sodium and chloride administered, length of stay, and morbidity (postoperative pancreatic fistula, POPF; acute kidney injury, AKI; ileus). The study included 169 patients, with a mean age of 64 ± 11.3 years. Following implementation of the intravenous fluid therapy protocol, there was a significant reduction in chloride and sodium loading. However, in the multivariable analysis, chloride administered (mmoL/kg) did not independently influence the length of stay; or rates of POPF, ileus, or AKI (p > 0.05). The findings suggested that a postoperative intravenous fluid therapy regimen did not significantly impact morbidity. Notably, there was a trend towards reduced length of stay within an increasingly comorbid patient cohort. This targeted fluid regimen appears to be safe for PD patients within the ERAS program. Further prospective research is needed to explore this area.

Captopril challenge test: an underutilized test in the diagnosis of primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension and is often underdiagnosed. This condition is associated with increased cardiovascular morbidity and mortality in comparison to age and blood pressure matched individuals with essential hypertension (EH). The diagnostic pathway for PA consists of three phases: screening, confirmatory testing, and subtyping. The lack of specificity in the screening step, which relies on the aldosterone to renin ratio, necessitates confirmatory testing. The Endocrine Society's clinical practice guideline suggests four confirmatory tests, including the fludrocortisone suppression test (FST), saline suppression test (SST), captopril challenge test (CCT), and oral sodium loading test (SLT). There is no universally accepted choice of confirmatory test, with practices varying among centers. The SST and FST are commonly used, but they can be resource-intensive, carry risks such as volume overload or hypokalemia, and are contraindicated in severe/uncontrolled HTN as well as in cardiac and renal impairment. In contrast, CCT is a safe and inexpensive alternative that can be performed in an outpatient setting and can be applied when other tests are contraindicated. Despite its simplicity and convenience, the variability in captopril dose, testing posture, and diagnostic threshold limit its widespread use. This narrative review evaluates the diagnostic accuracy of the CCT across different populations, addresses controversies in its usage, and proposes recommendations for its use in the diagnosis of PA. Furthermore, suggestions for future research aimed at promoting the wider utilization of the CCT as a simpler, safer, and more cost-effective diagnostic test are discussed.

Problems in the diagnosis of secondary arterial hypertension of adrenal origin

Primary hyperaldosteronism is the leading cause of secondary arterial hypertension of adrenal origin. Its prevalence is underestimated. This leads to late diagnosis, although a timely diagnosis can achieve a complete cure for the patient, ensure control of blood pressure and avoid the development of complications. The article discusses the prevalence of primary hyperaldosteronism, its etiology and pathogenesis, the mechanisms of formation of autonomous secretion of aldosterone, including with the combined production of cortisol. The main clinical effects of aldosterone hypersecretion, its role in the formation of complications in the cardiovascular system and metabolic control are discussed. The assessment of the main clinical effects of aldosterone hypersecretion and its role in the formation of complications from the cardiovascular system and metabolic control is given. The authors remind about risk groups in which screening should be carried out, about the stages of a diagnostic search for suspected primary hyperaldosteronism. For the primary test, a preliminary assessment of the level of plasma potassium is necessary, and if hypokalemia is detected, its correction. If the result of the primary test is false negative, retesting will be carried out with the transfer of patients to antihypertensive drugs with minimal effect on the renin-angiotensinaldosterone system. It is important to remember that confirmatory sodium loading tests are contraindicated in some patients. Computed tomography with contrast in combination with selective venous blood sampling in patients are the most significant methods for the topical diagnosis of primary hyperaldosteronism. The choice of treatment method and its effectiveness depend on their results.

FRI130 Usefulness Of The Upright Posture Test In The Diagnosis Of Primary Aldosteronism

Abstract Disclosure: N. Younes: None. M. St-Jean: None. M. Desrochers: None. I. Bourdeau: None. A. Lacroix: None. Objectives: Renin-independent aldosterone excess characterizes primary aldosteronism (PA). We have previously shown that PA is frequently regulated by aberrant stimuli, including the upright posture stimulation test (UPT), in which plasma aldosterone concentrations (PAC) increase in a renin-independent manner. In this study, we further examined the usefulness of UPT in diagnosing PA. Methods: We conducted a retrospective analysis of the medical records of 187 adult patients who underwent an UPT as part of their evaluation for possible PA and 25 control subjects, in 2 referral university centers between January 2011 and December 2021. UPT was conducted in an ambulatory setting, mostly in patients with potential false negative or borderline results of oral/IV saline confirmation tests. UPT was performed in a fasting state, early morning, 72 hours off beta-blockers, ACE, or ARBS. Patients were in a supine posture for 1 hour, followed by ambulation for 2 hours. Blood samples were collected for PAC, renin, and cortisol, at baseline and at 30 minutes intervals during ambulation. An abnormal response was defined as a ≥50% rise in PAC with a suppressed renin (≤10.1 ng/L or ≤1 ng/mL/h) and a cortisol increase ≤50%. Results: Median age of patients was 55.0 [IQR (46.0; 63.0)], 52.4% were female. 93.6% were taking at least one antihypertensive medication and 32% had hypokalemia. 43.5% did not have adrenal nodules at imaging. 76.5% (n=143) were diagnosed with PA, based on either IV/oral sodium load or UPT. When compared to controls, PA patients had higher basal PAC and lower basal renin levels (p&amp;lt;.0001) and achieved a higher maximal PAC and lower maximal renin (renin max) in response to posture [median PAC (IQR): 802.0 pmol/L (569.0, 1244.0) in PA v/s 624.0 pmol/L (500.0, 736.0) in controls, p=0.0081 and median renin 5.0 ng/L [IQR (3.0, 8.0)] in PA v/s 27.5 ng/L in controls (19.0, 46.0); p&amp;lt;.0001]. Renin max ≤10.1 had the best sensitivity and specificity for predicting PA (90% and 92%, respectively). 95.3% of PA patients increased PAC by at least 50% on UPT (median increase 363%), while renin remained suppressed. All 42 PA patients with a false negative (PAC ≤162 pmol/L) on IV saline test had a renin max ≤10.1 during UPT and 97.6% increased aldosterone by at least 50%. 84% of PA patients with a borderline response (162-240 pmol/L) on IV saline test, had a renin max ≤10.1 and all patients increased aldosterone by at least 50%. 42 patients underwent adrenal vein sampling: 50% had lateralized PA (potassium was lower than in bilateral PA, p=0.003). However, the aldosterone and renin response to UPT did not significantly differ between the two subtypes of PA. Conclusion: A renin-independent aldosterone increase during UPT can be used to confirm PA diagnosis, which was particularly useful in patients with false negative saline loading tests. Renin-independent PAC response to UPT occurred equally in lateralized and bilateral PA. Presentation: Friday, June 16, 2023

Salt-sensitive trait of normotensive individuals is associated with altered autonomous cardiac regulation: a randomized controlled intervention study.

Blood pressure (BP) responses to sodium intake show great variation, discriminating salt-sensitive (SS) from salt-resistant (SR) individuals. The pathophysiology behind salt sensitivity is still not fully elucidated. We aimed to investigate salt-induced effects on body fluid, vascular tone, and autonomic cardiac response with regard to BP change in healthy normotensive individuals. We performed a randomized crossover study in 51 normotensive individuals with normal body mass index and estimated glomerular filtration rate. Subjects followed both a low-Na+ diet (LSD, <50 mmol/day) and a high-Na+ diet (HSD, >200 mmol/day). Cardiac output, systemic vascular resistance (SVR), and cardiac autonomous activity, through heart rate variability and cross-correlation baroreflex sensitivity (xBRS), were assessed with noninvasive continuous finger BP measurements. In a subset, extracellular volume (ECV) was assessed by iohexol measurements. Subjects were characterized as SS if mean arterial pressure (MAP) increased ≥3 mmHg after HSD. After HSD, SS subjects (25%) showed a 6.1-mmHg (SD 1.9) increase in MAP. No differences between SS and SR in body weight, cardiac output, or ECV were found. SVR was positively correlated with Delta BP (r = 0.31, P = 0.03). xBRS and heart rate variability were significantly higher in SS participants compared to SR participants after both HSD and LSD. Sodium loading did not alter heart rate variability within groups. Salt sensitivity in normotensive individuals is associated with an inability to decrease SVR upon high salt intake that is accompanied by alterations in autonomous cardiac regulation, as reflected by decreased xBRS and heart rate variability. No discriminatory changes upon high salt were observed among salt-sensitive individuals in body weight and ECV.NEW & NOTEWORTHY Extracellular fluid expansion in normotensive individuals after salt loading is present in both salt-sensitive and salt-resistant individuals and is not discriminatory to the blood pressure response to sodium loading in a steady-state measurement. In normotensive subjects, the ability to sufficiently vasodilate seems to play a pivotal role in salt sensitivity. In a normotensive cohort, differences in sympathovagal balance are also present in low-salt conditions rather than being affected by salt loading. Whereas treatment and prevention of salt-sensitive blood pressure increase are mostly focused on renal sodium handling and extracellular volume regulation, our study suggests that an inability to adequately vasodilate and altered autonomous cardiac functioning are additional key players in the pathophysiology of salt-sensitive blood pressure increase.

Exploring the Drug-Loading and Release Ability of FucoPol Hydrogel Membranes.

The polysaccharide FucoPol has recently been shown to yield hydrogel membranes (HMs) characterized by good mechanical properties, biocompatibility, and anti-inflammatory activity that render them promising biomaterials for use in the biomedical field. Subsequently to such findings, envisaging their development into novel delivery systems for topical applications, in this study, FucoPol HMs prepared by crosslinking the biopolymer with iron cations were loaded with caffeine or diclofenac sodium as model drugs. Two loading methods, namely diffusion and mixing, were applied to evaluate the FucoPol's HM drug-loading capacity and entrapment efficiency. The diffusion method led to a higher caffeine loading (101.9 ± 19.1 mg/g) in the HM1_DCAF membranes, while the mixing method resulted in a higher diclofenac sodium loading (82.3 ± 5.1 mg/g) in the HM1_DDS membranes. The HM1_DCAF membranes were characterized by increased mechanical and rheological parameters, such as their hardness (130.0 ± 5.3 kPa) and storage modulus (1014.9 ± 109.7 Pa), compared to the HM1_DDS membranes that exhibited lower values (7.3 ± 1.2 kPa and 19.8 ± 3.8 Pa, respectively), probably due to leaching occurring during the drug-loading process. The release profiles revealed a fast release of both APIs from the membranes loaded by diffusion, while a prolonged and sustained release was obtained from the membranes loaded by mixing. Moreover, for all API-loaded membranes, the release mechanism followed Fickian diffusion, with the release rate being essentially governed by the diffusion process. These findings, together with their previously shown biological properties, support the suitability of the developed FucoPol HMs to be used as platforms for the topical delivery of drugs.