Tissue sodium excess is not hypertonic and reflects extracellular volume expansion.
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ABSTRACT:
SUBMITTER: Rossitto G
PROVIDER: S-EPMC7445299 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The renal distal nephron plays an important role in the maintenance of sodium balance, extra cellular volume and blood pressure. The degree of water transport, via aquaporin2 water channels (AQP2), and sodium transport, via epithelial sodium channels (ENaC) in renal collecting duct principal cells are reflected by the level of urinary excretion of AQP2 (u-AQP2) and the ?-fraction of ENaC (u-ENaC?). The effects of an acute intravenous volume load with isotonic saline, hypertonic saline and glucose on u-AQP2, u-ENaC? and underlying mechanisms have never been studied in a randomized, placebo-controlled trial in healthy humans.We studied the effects of 0.9% saline (23 ml/kg), 3% saline (7 ml/kg) and 5% glucose (23 ml/kg) on u-AQP2 and u-ENaC?, fractional sodium excretion (FENa), free water clearance (CH2O), and plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (ANG II) and aldosterone (Aldo) in a randomized, crossover study of 23 healthy subjects, who consumed a standardized diet, regarding calories, sodium and fluid for 4 days before each examination day.After isotonic saline infusion, u-AQP2 increased (27%). CH2O and u-ENaC? were unchanged, whereas FENa increased (123%). After hypertonic saline infusion, there was an increase in u-AQP2 (25%), u-ENaC? (19%) and FENa (96%), whereas CH2O decreased (-153%). After isotonic glucose infusion, there was a decrease in u-AQP2 (-16%), ENaC? (-10%) and FENa (-44%) whereas CH2O increased (164%). AVP remained unchanged after isotonic saline and glucose, but increased after hypertonic saline (139%). PRC, AngII and p-Aldo decreased after isotonic and hypertonic saline infusion, but not after glucose infusion.Volume expansion with 3% and 0.9% saline increased u-AQP2, while isotonic glucose decreased u-AQP2. Infusion of hypertonic saline increased u-ENaC?, whereas u-ENaC? was not significantly changed after isotonic saline and tended to decrease after glucose. Thus, the transport of water and sodium is changed both via the aquaporin 2 water channels and the epithelial sodium channels during all three types of volume expansion to regulate and maintain water- and sodium homeostasis in the body.Clinical Trial no: NCT01414088.
| S-EPMC3849534 | biostudies-literature
Project description:BackgroundSodium chloride (NaCl) loading and volume expansion suppress the renin-angiotensin-aldosterone system to reduce renal tubular reabsorption of NaCl and water, but effects on the sodium-chloride cotransporter (NCC) and relevant renal transmembrane proteins that are responsible for this modulation in humans are less well investigated.MethodsWe used urinary extracellular vesicles (uEVs) as an indirect readout to assess renal transmembrane proteins involved in NaCl and water homeostasis in 44 patients with hypertension who had repeatedly raised aldosterone/renin ratios undergoing infusion of 2 L of 0.9% saline over 4 hours.ResultsWhen measured by mass spectrometry in 13 patients, significant decreases were observed in NCC (median fold change [FC]=0.70); pendrin (FC=0.84); AQP2 (FC=0.62); and uEV markers, including ALIX (FC=0.65) and TSG101 (FC=0.66). Immunoblotting reproduced the reduction in NCC (FC=0.54), AQP2 (FC=0.42), ALIX (FC=0.52), and TSG101 (FC=0.55) in the remaining 31 patients, and demonstrated a significant decrease in phosphorylated NCC (pNCC; FC=0.49). However, after correction for ALIX, the reductions in NCC (FC=0.90) and pNCC (FC=1.00) were no longer apparent, whereas the significant decrease in AQP2 persisted (FC=0.62).ConclusionWe conclude that (1) decreases in NCC and pNCC, induced by acute NaCl loading and volume expansion, may be due to diluted post-test urines; (2) the lack of change of NCC and pNCC when corrected for ALIX, despite a fall in plasma aldosterone, may be due to the lack of change in plasma K+; and (3) the decrease in AQP2 may be due to a decrease in vasopressin in response to volume expansion.
| S-EPMC9438418 | biostudies-literature
Project description:Multifrequency bioimpedance spectroscopy (BIS) is an established method for assessing fluid status in chronic kidney disease (CKD). However, the technique is lacking in predictive value and accuracy. BIS algorithms assume constant tissue resistivity, which may vary with changing tissue ionic sodium concentration (Na+). This may introduce significant inaccuracies to BIS outputs. To investigate this, we used 23Na magnetic resonance imaging (MRI) to measure Na+ in muscle and subcutaneous tissues of 10 healthy controls (HC) and 20 patients with CKD 5 (not on dialysis). The extracellular (Re) and intracellular (Ri) resistance, tissue capacitance, extracellular (ECW) and total body water (TBW) were measured using BIS. Tissue water content was assessed using proton density-weighted MRI with fat suppression. BIS-derived volume indices were comparable in the two groups (OH: HC - 0.4?±?0.9 L vs. CKD 0.5?±?1.9 L, p?=?0.13). However, CKD patients had higher Na+ (HC 21.2?±?3.0, CKD 25.3?±?7.4 mmol/L; p?=?0.04) and significantly lower Re (HC 693?±?93.6, CKD 609?±?74.3 Ohms; p?=?0.01); Ri and capacitance did not vary. Na+ showed a significant inverse linear relationship to Re (rs?=?- 0.598, p?<?0.01) but not Ri. This relationship of Re (y) and Na+ (x) is described through equation y?=?- 7.39x?+?814. A 20% increase in tissue ionic Na+ is likely to overestimate ECW by 1.2-2.4L. Tissue Na+ concentration has a significant inverse linear relationship to Re. BIS algorithms to account for this effect could improve prediction accuracy of bioimpedance derived fluid status in CKD.
| S-EPMC7007413 | biostudies-literature
Project description:Whether increasing exposure to dietary phosphorus can lead to adverse clinical outcomes in healthy people is not clear. In this open-label prospective cross-over study, we are to explore the impact of various dietary phosphorus intake on mineral, sodium metabolisms and blood pressure in young healthy adults. There were 3 separate study periods of 5 days, each with a 5 days washout period between different diets interventions. Six young healthy male volunteers with normal nutrition status were recruited in Phase I Clinical Research Center and sequentially exposed to the following diets: (a) normal-phosphorus diet (NPD): 1500 mg/d, (b) low-phosphorus diet (LPD): 500 mg/d, (c) high-phosphorus diet (HPD): 2300 mg/d. HPD induced a significant rise in daily average serum phosphate (1.47 ± 0.02 mmol/L [4.56 ± 0.06 mg/dl]) compared to NPD (1.34 ± 0.02 mmol/L [4.15 ± 0.06 mg/dL]) and LPD (1.17 ± 0.02 mmol/L [3.63 ± 0.06 mg/dL]) (p < .05). Daily average levels of serum parathyroid hormone and fibroblast growth factor 23 in HPD were significantly higher, and serum 1,25(OH)2 D3 was remarkably lower than those in LPD. HPD induced a significant decrease in daily average serum aldosterone and an increase in daily average atrial natriuretic peptide level compared to LPD. The 24-hour urine volume in HPD subjects was less than that in LPD subjects. HPD significantly increased daily average systolic blood pressure by 6.02 ± 1.24 mm Hg compared to NPD and by 8.58 ± 1.24mm Hg compared to LPD (p < .05). Our study provides the first evidence that 5-day high-phosphorus diet can induce elevation in SBP in young healthy adults, which may due to volume expansion.
| S-EPMC8678725 | biostudies-literature
Project description:Embryonic growth occurs predominately by an increase in cell number; little is known about growth mechanisms later in development when fibrous tissues account for the bulk of adult vertebrate mass. We present a model for fibrous tissue growth based on 3D-electron microscopy of mouse tendon. We show that the number of collagen fibrils increases during embryonic development and then remains constant during postnatal growth. Embryonic growth was explained predominately by increases in fibril number and length. Postnatal growth arose predominately from increases in fibril length and diameter. A helical crimp structure was established in embryogenesis, and persisted postnatally. The data support a model where the shape and size of tendon is determined by the number and position of embryonic fibroblasts. The collagen fibrils that these cells synthesise provide a template for postnatal growth by structure-based matrix expansion. The model has important implications for growth of other fibrous tissues and fibrosis.
| S-EPMC4438642 | biostudies-literature
Project description:The purpose of this work was to develop a novel method to disentangle the intra- and extracellular components of the total sodium concentration (TSC) in breast cancer from a combination of proton ([Formula: see text]H) and sodium ([Formula: see text]) magnetic resonance imaging (MRI) measurements. To do so, TSC is expressed as function of the intracellular sodium concentration ([Formula: see text]), extracellular volume fraction (ECV) and the water fraction (WF) based on a three-compartment model of the tissue. TSC is measured from [Formula: see text] MRI, ECV is calculated from baseline and post-contrast [Formula: see text]H [Formula: see text] maps, while WF is measured with a [Formula: see text]H chemical shift technique. [Formula: see text] is then extrapolated from the model. Proof-of-concept was demonstrated in three healthy subjects and two patients with triple negative breast cancer. In both patients, TSC was two to threefold higher in the tumor than in normal tissue. This alteration mainly resulted from increased [Formula: see text] ([Formula: see text] 30 mM), which was [Formula: see text] 130% greater than in healthy conditions (10-15 mM) while the ECV was within the expected range of physiological values (0.2-0.25). Multinuclear MRI shows promise for disentangling [Formula: see text] and ECV by taking advantage of complementary [Formula: see text]H and [Formula: see text] measurements.
| S-EPMC7933187 | biostudies-literature
Project description:In this feasibility study we propose a method based on sodium magnetic resonance imaging (MRI) for estimating simultaneously the intracellular sodium concentration (C1, in mM) and the extracellular volume fraction (α) in grey and white matters (GM, WM) in brain in vivo. Mean C1 over five healthy volunteers was measured ~11 mM in both GM and WM, mean α was measured ~0.22 in GM and ~0.18 in WM, which are in close agreement with standard values for healthy brain tissue (C1 ~ 10-15 mM, α ~ 0.2). Simulation of 'fluid' and 'solid' inclusions were accurately detected on both the C1 and α 3D maps and in the C1 and α distributions over whole GM and WM. This non-invasive and quantitative method could provide new biochemical information for assessing ion homeostasis and cell integrity in brain and help the diagnosis of early signs of neuropathologies such as multiple sclerosis, Alzheimer's disease, brain tumors or stroke.
| S-EPMC4762219 | biostudies-literature
Project description:ObjectivesThis study tested whether myocardial extracellular volume (ECV) is increased in patients with hypertension and atrial fibrillation (AF) undergoing pulmonary vein isolation and whether there is an association between ECV and post-procedural recurrence of AF.BackgroundHypertension is associated with myocardial fibrosis, an increase in ECV, and AF. Data linking these findings are limited. T1 measurements pre-contrast and post-contrast in a cardiac magnetic resonance (CMR) study provide a method for quantification of ECV.MethodsConsecutive patients with hypertension and recurrent AF referred for pulmonary vein isolation underwent a contrast CMR study with measurement of ECV and were followed up prospectively for a median of 18 months. The endpoint of interest was late recurrence of AF.ResultsPatients had elevated left ventricular (LV) volumes, LV mass, left atrial volumes, and increased ECV (patients with AF, 0.34 ± 0.03; healthy control patients, 0.29 ± 0.03; p < 0.001). There were positive associations between ECV and left atrial volume (r = 0.46, p < 0.01) and LV mass and a negative association between ECV and diastolic function (early mitral annular relaxation [E'], r = -0.55, p < 0.001). In the best overall multivariable model, ECV was the strongest predictor of the primary outcome of recurrent AF (hazard ratio: 1.29; 95% confidence interval: 1.15 to 1.44; p < 0.0001) and the secondary composite outcome of recurrent AF, heart failure admission, and death (hazard ratio: 1.35; 95% confidence interval: 1.21 to 1.51; p < 0.0001). Each 10% increase in ECV was associated with a 29% increased risk of recurrent AF.ConclusionsIn patients with AF and hypertension, expansion of ECV is associated with diastolic function and left atrial remodeling and is a strong independent predictor of recurrent AF post-pulmonary vein isolation.
| S-EPMC3900879 | biostudies-literature
Project description:Regulation of cell volume is essential for tissue homeostasis and cell viability. In response to hypertonic stress, cells need rapid electrolyte influx to compensate water loss and to prevent cell death in a process known as regulatory volume increase (RVI). However, the molecular component able to trigger such process was unknown to date. Using a genome wide CRISPR/Cas9 screen, we identified LRRC8A, which encodes a chloride channel subunit, as the gene most associated with cell survival under hypertonic conditions. Hypertonicity activates the p38 stress-activated protein kinase pathway and its downstream MSK1 kinase, which phosphorylates and activates LRRC8A. LRRC8A-mediated Cl efflux facilitates activation of the with-no-lysine (WNK) kinase pathway, which in turn, promotes electrolyte influx via Na+ /K+ /2Cl cotransporter (NKCC) and RVI under hypertonic stress. LRRC8A-S217A mutation impairs channel activation by MSK1, resulting in reduced RVI and cell survival. In summary, LRRC8A is key to bidirectional osmotic stress responses and cell survival under hypertonic conditions.
2021-05-29 | GSE158316 | GEO
Project description:Intradialytic blood pressure (BP) profiles have been associated with all-cause mortality, but its pathophysiology remains unknown. We tested the hypothesis that intradialytic changes in BP reflect excess volume.The dry weight reduction in hypertensive haemodialysis patients (DRIP) trial probed dry weight in 100 prevalent haemodialysis patients; 50 patients who did not have their dry weight probed served as time controls. In this post hoc analysis, intradialytic BP was recorded at each of the 30 dialysis treatments during the trial. The slope of intradialytic BP over dialysis was calculated by the log of BP regressed over time. Using a linear mixed model, we compared these slopes between control and ultrafiltration groups at baseline and over time, tested the effect of dry weight reduction on these slopes and finally tested the ability of change in intradialytic slopes to predict change in interdialytic systolic BP.At baseline, intradialytic systolic and diastolic BP dropped at a rate of ~3%/h (P < 0.0001). Over the course of the trial, compared to the control group, the slopes steepened in the ultrafiltration group for systolic but not diastolic BP. Those who lost the most post-dialysis weight from baseline to 4 weeks and baseline to 8 weeks also experienced the greatest steepening of slopes. Each percent per hour steepening of the intradialytic systolic BP slope was associated with 0.71 mmHg [95% confidence interval (CI) 0.01-1.42, P = 0. 048] reduction in interdialytic ambulatory systolic pressure.Intradialytic BP changes appear to be associated with change in dry weight among haemodialysis patients. Among long-term haemodialysis patients, intradialytic hypertension may, thus, be a sign of volume overload.
| S-EPMC2948838 | biostudies-literature