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Kidney360 Nov 2022Elevated abundance of sodium-chloride cotransporter (NCC) and phosphorylated NCC (pNCC) are potential markers of primary aldosteronism (PA), but these effects may be...
BACKGROUND
Elevated abundance of sodium-chloride cotransporter (NCC) and phosphorylated NCC (pNCC) are potential markers of primary aldosteronism (PA), but these effects may be driven by hypokalemia.
METHODS
We measured plasma potassium in patients with PA. If potassium was <4.0 mmol/L, patients were given sufficient oral potassium chloride (KCl) over 24 hours to achieve as close to 4.0 mmol/L as possible. Clinical chemistries were assessed, and urinary extracellular vesicles (uEVs) were examined to investigate effects on NCC.
RESULTS
Among 21 patients with PA who received a median total dose of 6.0 g (2.4-16.8 g) of KCl, increases were observed in plasma potassium (from 3.4 to 4.0 mmol/L; <0.001), aldosterone (from 305 to 558 pmol/L; 0.01), and renin (from 1.2 to 2.5 mIU/L; <0.001), whereas decreases were detected in uEV levels of NCC (median fold change [FC]=0.71 [0.09-1.99]; 0.02), pT60-NCC (FC=0.84 [0.06-1.66]; 0.05), and pT55/60-NCC (FC=0.67 [0.08-2.42]; 0.02). By contrast, in 10 patients with PA who did not receive KCl, there were no apparent changes in plasma potassium, NCC abundance, and phosphorylation status, but increases were observed in plasma aldosterone (from 178 to 418 pmol/L; 0.006) and renin (from 2.0 to 3.0 mU/L; 0.009). Plasma potassium correlated inversely with uEV levels of NCC ( =0.11; 0.01), pT60-NCC ( =0.11; =0.01), and pT55/60-NCC ( =0.11; =0.01).
CONCLUSIONS
Acute oral KCl loading replenished plasma potassium in patients with PA and suppressed NCC abundance and phosphorylation, despite a significant rise in plasma aldosterone. This supports the view that potassium supplementation in humans with PA overrides the aldosterone stimulatory effect on NCC. The increased plasma aldosterone in patients with PA without KCl supplementation may be due to aldosterone response to posture challenge.
Topics: Humans; Sodium Chloride Symporters; Aldosterone; Potassium Chloride; Renin; Phosphorylation; Potassium; Hyperaldosteronism; Dietary Supplements
PubMed: 36514401
DOI: 10.34067/KID.0003632022 -
International Journal of Molecular... Jan 2021Stroke is one of the major culprits responsible for morbidity and mortality worldwide, and the currently available pharmacological strategies to combat this global... (Review)
Review
Stroke is one of the major culprits responsible for morbidity and mortality worldwide, and the currently available pharmacological strategies to combat this global disease are scanty. Cation-chloride cotransporters (CCCs) are expressed in several tissues (including neurons) and extensively contribute to the maintenance of numerous physiological functions including chloride homeostasis. Previous studies have implicated two CCCs, the Na-K-Cl and K-Cl cotransporters (NKCCs and KCCs) in stroke episodes along with their upstream regulators, the with-no-lysine kinase (WNKs) family and STE20/SPS1-related proline/alanine rich kinase (SPAK) or oxidative stress response kinase (OSR1) via a signaling pathway. As the WNK-SPAK/OSR1 pathway reciprocally regulates NKCC and KCC, a growing body of evidence implicates over-activation and altered expression of NKCC1 in stroke pathology whilst stimulation of KCC3 during and even after a stroke event is neuroprotective. Both inhibition of NKCC1 and activation of KCC3 exert neuroprotection through reduction in intracellular chloride levels and thus could be a novel therapeutic strategy. Hence, this review summarizes the current understanding of functional regulations of the CCCs implicated in stroke with particular focus on NKCC1, KCC3, and WNK-SPAK/OSR1 signaling and discusses the current and potential pharmacological treatments for stroke.
Topics: Homeostasis; Humans; Neurons; Phosphorylation; Protein Serine-Threonine Kinases; Signal Transduction; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Potassium-Chloride Symporters; Stroke; Symporters; WNK Lysine-Deficient Protein Kinase 1; K Cl- Cotransporters
PubMed: 33513812
DOI: 10.3390/ijms22031232 -
Hypertension (Dallas, Tex. : 1979) Mar 2024Excess dietary sodium intake and insufficient dietary potassium intake are both well-established risk factors for hypertension. Despite some successful initiatives,... (Review)
Review
Excess dietary sodium intake and insufficient dietary potassium intake are both well-established risk factors for hypertension. Despite some successful initiatives, efforts to control hypertension by improving dietary intake have largely failed because the changes required are mostly too hard to implement. Consistent recent data from randomized controlled trials show that potassium-enriched, sodium-reduced salt substitutes are an effective option for improving consumption levels and reducing blood pressure and the rates of cardiovascular events and deaths. Yet, salt substitutes are inconsistently recommended and rarely used. We sought to define the extent to which evidence about the likely benefits and harms of potassium-enriched salt substitutes has been incorporated into clinical management by systematically searching guidelines for the management of hypertension or chronic kidney disease. We found incomplete and inconsistent recommendations about the use of potassium-enriched salt substitutes in the 32 hypertension and 14 kidney guidelines that we reviewed. Discussion among the authors identified the possibility of updating clinical guidelines to provide consistent advice about the use of potassium-enriched salt for hypertension control. Draft wording was chosen to commence debate and progress consensus building: strong recommendation for patients with hypertension-potassium-enriched salt with a composition of 75% sodium chloride and 25% potassium chloride should be recommended to all patients with hypertension, unless they have advanced kidney disease, are using a potassium supplement, are using a potassium-sparing diuretic, or have another contraindication. We strongly encourage clinical guideline bodies to review their recommendations about the use of potassium-enriched salt substitutes at the earliest opportunity.
Topics: Humans; Potassium; Hypertension; Diet; Potassium Chloride; Renal Insufficiency, Chronic; Sodium Chloride, Dietary; Blood Pressure
PubMed: 38284271
DOI: 10.1161/HYPERTENSIONAHA.123.21343 -
The Journal of Nutrition Sep 2023Human milk is the preferred diet for very low birth weight (VLBW, <1500 g) infants. When mother's own milk is unable to meet the needs of VLBW infants, donor human milk...
BACKGROUND
Human milk is the preferred diet for very low birth weight (VLBW, <1500 g) infants. When mother's own milk is unable to meet the needs of VLBW infants, donor human milk (DHM) is the preferred alternative. Unfortunately, the composition of DHM remains elusive and no comparative studies between preterm human milk and DHM have been performed previously.
OBJECTIVES
We aimed to analyze the nutrient content of commercial pooled DHM and compare nutrient content in DHM with that of early and mature preterm human milk.
METHODS
We analyzed nutrient content in 15 DHM samples provided from 7 commercial milk banks including calories, carbohydrate, fat, protein, sodium, chloride, potassium, zinc, calcium, phosphorus, magnesium, and vitamin D and compared each nutrient to early (7 d of life) and mature (28 d of life) preterm human milk samples (n = 28-36 per nutrient, gestational age = 28 ± 3 wk). Protein-to-energy ratio and carbohydrate-to-nonprotein energy ratio were calculated for each sample and compared.
RESULTS
Mean values for all macro- and micronutrients in DHM are reported. In comparison to early or mature preterm human milk, DHM had significantly lower protein, sodium, chloride, potassium, and zinc content. Calorie, carbohydrate, calcium, phosphorus, magnesium, and vitamin D content did not differ statistically between DHM and early or mature preterm human milk. Fat content was modestly lower in early but not mature human milk when compared with DHM.
CONCLUSIONS
We provide mean values for several macro- and micronutrients for DHM and identify key differences between DHM and preterm human milk, which may be considered when designing human milk-based feeding plans. This study was registered at clinicaltrials.gov as NCT05742815.
Topics: Infant, Newborn; Infant; Humans; Adult; Milk, Human; Infant, Premature; Calcium; Magnesium; Potassium Chloride; Nutrients; Sodium; Phosphorus; Potassium; Carbohydrates; Micronutrients; Zinc
PubMed: 37517552
DOI: 10.1016/j.tjnut.2023.07.012 -
Journal of the American Society of... Sep 2022Observational studies suggest that adequate dietary potassium intake (90-120 mmol/day) may be renoprotective, but the effects of increasing dietary potassium and the...
BACKGROUND
Observational studies suggest that adequate dietary potassium intake (90-120 mmol/day) may be renoprotective, but the effects of increasing dietary potassium and the risk of hyperkalemia are unknown.
METHODS
This is a prespecified analysis of the run-in phase of a clinical trial in which 191 patients (age 68±11 years, 74% males, 86% European ancestry, eGFR 31±9 ml/min per 1.73 m, 83% renin-angiotensin system inhibitors, 38% diabetes) were treated with 40 mmol potassium chloride (KCl) per day for 2 weeks.
RESULTS
KCl supplementation significantly increased urinary potassium excretion (72±24 to 107±29 mmol/day), plasma potassium (4.3±0.5 to 4.7±0.6 mmol/L), and plasma aldosterone (281 [198-431] to 351 [241-494] ng/L), but had no significant effect on urinary sodium excretion, plasma renin, BP, eGFR, or albuminuria. Furthermore, KCl supplementation increased plasma chloride (104±3 to 105±4 mmol/L) and reduced plasma bicarbonate (24.5±3.4 to 23.7±3.5 mmol/L) and urine pH (all <0.001), but did not change urinary ammonium excretion. In total, 21 participants (11%) developed hyperkalemia (plasma potassium 5.9±0.4 mmol/L). They were older and had higher baseline plasma potassium.
CONCLUSIONS
In patients with CKD stage G3b-4, increasing dietary potassium intake to recommended levels with potassium chloride supplementation raises plasma potassium by 0.4 mmol/L. This may result in hyperkalemia in older patients or those with higher baseline plasma potassium. Longer-term studies should address whether cardiorenal protection outweighs the risk of hyperkalemia. NCT03253172.
Topics: Male; Humans; Aged; Middle Aged; Female; Potassium Chloride; Hyperkalemia; Potassium, Dietary; Potassium; Renal Insufficiency, Chronic; Dietary Supplements
PubMed: 35609996
DOI: 10.1681/ASN.2022020147 -
Molecules (Basel, Switzerland) Dec 2023The flotation agent is an important collector in the production of potassium chloride and is brought into the crystallization stage with the reflux of the mother liquor....
The flotation agent is an important collector in the production of potassium chloride and is brought into the crystallization stage with the reflux of the mother liquor. Octadecylamine Hydrochloride (ODA), 1-Dodecylamine Hydrochloride (DAH) and Sodium 1-dodecanesulfonate (SDS) were selected to study their effect on the nucleation of potassium chloride. Focused Beam Reflectance Measurement was used to collect the nucleation-induced periods of KCl in the presence of flotation agents at different supersaturations. Then, empirical equations, classical nucleation theory and growth mechanism equations were employed for data analysis. It was found that the presence of flotation agents increased the nucleation sequence , and (ODA) > (SDS) > (DAH) > (HO). In addition, the interfacial energy data obtained using classical nucleation theory suggest that the flotation agents used in our paper promoted the homogeneous nucleation of KCl (reduced from 5.3934 mJ·m to 5.1434 mJ·m) and inhibited the heterogeneous nucleation of KCl (increased from 2.8054 mJ·m to 3.6004 mJ·m). This investigation also revealed that the growth of potassium chloride was consistent with the 2D nucleation-mediated growth mechanism, and the addition of flotation agent did not change the growth mechanism of potassium chloride. Finally, the particle size distribution results were exactly consistent with the order of nucleation order . The study of nucleation kinetics and growth mechanisms of different flotation agents on potassium chloride can provide guidance for optimizing the production process of potassium chloride and developing new flotation agents.
PubMed: 38067652
DOI: 10.3390/molecules28237923 -
Journal of the American Chemical Society Aug 2022Chalcogen bonding (ChB) is rapidly rising to prominence in supramolecular chemistry as a powerful sigma (σ)-hole-based noncovalent interaction, especially for...
Chalcogen bonding (ChB) is rapidly rising to prominence in supramolecular chemistry as a powerful sigma (σ)-hole-based noncovalent interaction, especially for applications in the field of molecular recognition. Recent studies have demonstrated ChB donor strength and potency to be remarkably sensitive to local electronic environments, including redox-switchable on/off anion binding and sensing capability. Influencing the unique electronic and geometric environment sensitivity of ChB interactions through simultaneous cobound metal cation recognition, herein, we present the first potassium chloride-selective heteroditopic ion-pair receptor. The direct conjugation of benzo-15-crown-5 ether (B15C5) appendages to Te centers in a bis-tellurotriazole framework facilitates alkali metal halide (MX) ion-pair binding through the formation of a cofacial intramolecular bis-B15C5 M (M = K, Rb, Cs) sandwich complex and bidentate ChB···X formation. Extensive quantitative H NMR ion-pair affinity titration experiments, solid-liquid and liquid-liquid extraction, and U-tube transport studies all demonstrate unprecedented KCl selectivity over all other group 1 metal chlorides. It is demonstrated that the origin of the receptor's ion-pair binding cooperativity and KCl selectivity arises from an electronic polarization of the ChB donors induced by the cobound alkali metal cation. Importantly, the magnitude of this switch on Te-centered electrophilicity, and therefore anion-binding affinity, is shown to correlate with the inherent Lewis acidity of the alkali metal cation. Extensive computational DFT investigations corroborated the experimental alkali metal cation-anion ion-pair binding observations for halides and oxoanions.
Topics: Anions; Cations; Chalcogens; Chlorides; Metals, Alkali; Potassium Chloride
PubMed: 35930460
DOI: 10.1021/jacs.2c05333 -
ASN Neuro 2020Elevated extracellular potassium chloride is widely used to achieve membrane depolarization of cultured neurons. This technique has illuminated mechanisms of calcium... (Review)
Review
Elevated extracellular potassium chloride is widely used to achieve membrane depolarization of cultured neurons. This technique has illuminated mechanisms of calcium influx through L-type voltage sensitive calcium channels, activity-regulated signaling, downstream transcriptional events, and many other intracellular responses to depolarization. However, there is enormous variability in these treatments, including durations from seconds to days and concentrations from 3mM to 150 mM KCl. Differential effects of these variable protocols on neuronal activity and transcriptional programs are underexplored. Furthermore, potassium chloride treatments are criticized for being poor representatives of phenomena and are questioned for their effects on cell viability. In this review, we discuss the intracellular consequences of elevated extracellular potassium chloride treatment , the variability of such treatments in the literature, the strengths and limitations of this tool, and relevance of these studies to brain functions and dysfunctions.
Topics: Action Potentials; Animals; Calcium Channels, L-Type; Humans; Membrane Potentials; Neuromuscular Depolarizing Agents; Neurons; Potassium Chloride
PubMed: 33256465
DOI: 10.1177/1759091420974807 -
Hypertension (Dallas, Tex. : 1979) Feb 2020Use of salt substitutes containing potassium chloride is a potential strategy to reduce sodium intake, increase potassium intake, and thereby lower blood pressure and... (Review)
Review
Use of salt substitutes containing potassium chloride is a potential strategy to reduce sodium intake, increase potassium intake, and thereby lower blood pressure and prevent the adverse consequences of high blood pressure. In this review, we describe the rationale for using potassium-enriched salt substitutes, summarize current evidence on the benefits and risks of potassium-enriched salt substitutes and discuss the implications of using potassium-enriched salt substitutes as a strategy to lower blood pressure. A benefit of salt substitutes that contain potassium chloride is the expected reduction in dietary sodium intake at the population level because of reformulation of manufactured foods or replacement of sodium chloride added to food during home cooking or at the dining table. There is empirical evidence that replacement of sodium chloride with potassium-enriched salt substitutes lowers systolic and diastolic blood pressure (average net Δ [95% CI] in mm Hg: -5.58 [-7.08 to -4.09] and -2.88 [-3.93 to -1.83], respectively). The risks of potassium-enriched salt substitutes include a possible increased risk of hyperkalemia and its principal adverse consequences: arrhythmias and sudden cardiac death, especially in people with conditions that impair potassium excretion such as chronic kidney disease. There is insufficient evidence regarding the effects of potassium-enriched salt substitutes on the occurrence of hyperkalemia. There is a need for additional empirical research on the effect of increasing dietary potassium and potassium-enriched salt substitutes on serum potassium levels and the risk of hyperkalemia, as well as for robust estimation of the population-wide impact of replacing sodium chloride with potassium-enriched salt substitutes.
Topics: Blood Pressure; Diet, Sodium-Restricted; Humans; Hypertension; Potassium Chloride; Risk Assessment; Sodium Chloride, Dietary; Water-Electrolyte Balance
PubMed: 31838902
DOI: 10.1161/HYPERTENSIONAHA.119.13241 -
Hypertension (Dallas, Tex. : 1979) Feb 2021The thiazide-sensitive sodium-chloride cotransporter (NCC;SLC12A3) is central to sodium and blood pressure regulation. Metabolic syndrome induces NCC upregulation...
The thiazide-sensitive sodium-chloride cotransporter (NCC;SLC12A3) is central to sodium and blood pressure regulation. Metabolic syndrome induces NCC upregulation generating sodium-sensitive hypertension in experimental animal models. We tested the role of NCC in sodium sensitivity in hypertensive humans with metabolic syndrome. Conversely, oral potassium induces NCC downregulation producing potassium-induced natriuresis. We determined the time course and magnitude of potassium-induced natriuresis compared with the natriuresis following hydrochlorothiazide (HCTZ) as a reference standard. We studied 19 obese hypertensive humans with metabolic syndrome during 13-day inpatient confinement. We determined sodium sensitivity by change in 24-hour mean systolic pressure by automated monitor from days 5 (low sodium) to 10 (high sodium). We determined NCC activity by standard 50 mg HCTZ sensitivity test (day 11). We determined potassium-induced natriuresis following 35 mmol KCl (day 13). We determined (1) whether NCC activity was greater in sodium-sensitive versus sodium-resistant participants and correlated with sodium sensitivity and (2) time course and magnitude of potassium-induced natriuresis following 35 mmol KCl directly compared with 50 mg HCTZ. NCC activity was not greater in sodium-sensitive versus sodium-resistant humans and did not correlate with sodium sensitivity. Thirty-five-millimoles KCl produced a rapid natriuresis approximately half that of 50 mg HCTZ with a greater kaliuresis. Our investigation tested a key hypothesis regarding NCC activity in human hypertension and characterized potassium-induced natriuresis following 35 mmol KCl compared with 50 mg HCTZ. In obese hypertensive adults with metabolic syndrome ingesting a high-sodium diet, 35 mmol KCl had a net natriuretic effect approximately half that of 50 mg HCTZ.
Topics: Adult; Aged; Blood Pressure; Female; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged; Natriuresis; Potassium Chloride; Sodium; Sodium Chloride Symporters; Sodium, Dietary
PubMed: 33390050
DOI: 10.1161/HYPERTENSIONAHA.120.15933