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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 -
Environmental Toxicology and Chemistry May 2024The ASTM International standard test method for freshwater mussels (E2455-13) recommends 4-week toxicity testing with juveniles to evaluate chronic effects on survival...
The ASTM International standard test method for freshwater mussels (E2455-13) recommends 4-week toxicity testing with juveniles to evaluate chronic effects on survival and growth. However, concerns remain that the method may not adequately address the sensitivity of mussels to longer term exposures (>4 weeks), particularly in relation to potential reproductive impairments. No standard method directly evaluates toxicant effects on mussel reproduction. The objectives of the present study were to (1) evaluate toxicity endpoints related to reproduction in fatmucket (Lampsilis siliquoidea) using two common reference toxicants, potassium chloride (KCl) and nickel (Ni); (2) evaluate the survival and growth of juvenile fatmucket in standard 4-week and longer term (12-week) KCl and Ni tests following a method refined from the standard method; and (3) compare the sensitivity of the reproductive endpoints with the endpoints obtained from the juvenile mussel tests. Reproductive toxicity tests were conducted by first exposing female fatmucket brooding mature larvae (glochidia) to five test concentrations of KCl and Ni for 6 weeks. Subsamples of the glochidia were then removed from the adults to determine three reproductive endpoints: (1) the viability of brooded glochidia; (2) the viability of free glochidia in a 24-h exposure to the same toxicant concentrations as their mother; and (3) the success of glochidia parasitism on host fish. Mean viability of brooded glochidia was significantly reduced in the high KCl concentration (26 mg K/L) relative to the control, with a 20% effect concentration (EC20) of 14 mg K/L, but there were no significant differences between the control and any Ni treatment (EC20 > 95 µg Ni/L). The EC20s for viability of free glochidia after the additional 24-h exposure and parasitism success were similar to the EC20s of brooded glochidia. The EC20s based on the most sensitive biomass endpoint in the 4-week juvenile tests were 15 mg K/L and 91 µg Ni/L, similar to or greater than the EC20s from the reproductive KCl and Ni tests, respectively. When exposure duration in the juvenile tests was extended from 4 to 12 weeks, the EC20s decreased by more than 50% in the KCl test but by only 8% in the Ni test. Overall, these results indicate that a standard 4-week test with juvenile mussels can prove effective for estimating effects in chronic exposures with different life stages although a longer term 12-week exposure with juvenile mussels may reveal higher sensitivity of mussels to some toxicants, such as KCl. Environ Toxicol Chem 2024;43:1097-1111. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Topics: Animals; Nickel; Reproduction; Water Pollutants, Chemical; Potassium Chloride; Female; Bivalvia; Unionidae
PubMed: 38488680
DOI: 10.1002/etc.5843 -
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 -
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 -
Regional Anesthesia and Pain Medicine Oct 2021Administration of the wrong drug via the epidural or intrathecal route can cause devastating consequences. Because of the commonality of potassium replacement therapy... (Review)
Review
BACKGROUND
Administration of the wrong drug via the epidural or intrathecal route can cause devastating consequences. Because of the commonality of potassium replacement therapy coupled to its potential neurotoxic profile, we suspected that injuries related to this drug error would be present in the literature.
OBJECTIVES
We aimed to identify clinical characteristics associated with the inadvertent administration of potassium chloride (KCl) during neuraxial anesthesia. Our secondary objective was to identify human factors that may have been associated.
EVIDENCE REVIEW
Published reports of neuraxial administration of KCl in humans were searched using Medline and Google Scholar. Error reports in any language were included.
FINDINGS
25 case reports/series reported administration of KCl via epidural (25 patients) or intrathecal routes (three patients). There were six cases during interventional pain procedures, five cases in operating rooms and 17 in wards or intensive care units. Neuraxial KCl caused paraplegia in 22 patients. Mechanical ventilation was instituted in 11 of 28 patients. Three patients died. Epidural (eight patients) and spinal (two patients) lavage were performed to minimize consequences. A correctly prepared KCl infusion was connected to the epidural catheter for nine patients on wards (32%; 95% upper confidence limit: 48%) due to epidural-intravenous line confusion. Among the other 19 errors, KCl was confused with normal saline for 13 patients or local anesthetic in three patients. A wide range of concentrations and doses of KCl were administered. Variable use of intravenous steroid (13 patients) and epidural saline (eight patients) was found among patients who received epidural KCl. Human factors identified included incorrect visual perception, inadequate monitoring of infusions and substandard practice related to neuraxial anesthesia or analgesia.
CONCLUSIONS
KCl administration via epidural or intrathecal route has been reported to cause catastrophic consequences.
Topics: Analgesia; Anesthesia, Epidural; Anesthetics, Local; Humans; Injections, Spinal; Potassium Chloride
PubMed: 34380745
DOI: 10.1136/rapm-2021-102933 -
FP Essentials Aug 2017Oral electrolyte solutions are used widely for rehydration in diarrheal illness and to maintain hydration during vigorous exercise. In diarrheal illness, an oral... (Review)
Review
Oral electrolyte solutions are used widely for rehydration in diarrheal illness and to maintain hydration during vigorous exercise. In diarrheal illness, an oral rehydration solution (ORS) typically is preferred over intravenous fluids except for patients with severe dehydration. The preferred ORS is one similar to the glucose-containing reduced osmolarity World Health Organization ORS. There also are polymer-based solutions that use rice or wheat as the source of carbohydrates but these are not widely recommended. Use of other liquids, such as sport drinks, juice, soft drinks, and chicken broth is not recommended, though these can be considered for patients with no or mild dehydration. For maintaining hydration during exercise, particularly vigorous high-intensity exercise, recommendations are to consume fluids (ie, 5 to 7 mL/kg) and a sodium-containing snack at least 4 hours before. During exercise, individuals require 200 to 800 mL/hour of liquid that should contain 20 to 30 mEq/L of sodium. Carbohydrate intake is recommended during high-intensity exercise. Intake of excessive sodium-free fluids should be avoided to prevent exercise-induced hyponatremia. Additional fluids (ie, 1.5 L/kg of weight lost) can be consumed after exercise to restore hydration. Vitamin and mineral supplements are not recommended routinely for athletes unless known deficiencies exist.
Topics: Bicarbonates; Dehydration; Diarrhea; Exercise; Fluid Therapy; Glucose; Humans; Potassium Chloride; Rehydration Solutions; Sodium Chloride; Water-Electrolyte Imbalance
PubMed: 28806049
DOI: No ID Found -
Journal of the Mechanical Behavior of... Apr 2023Smooth muscle cells contribute to the mechanical function of various soft tissues, however, their contribution to the viscoelastic response when subjected to multiaxial...
Smooth muscle cells contribute to the mechanical function of various soft tissues, however, their contribution to the viscoelastic response when subjected to multiaxial loading remains unknown. The vagina is a fibromuscular viscoelastic organ that is exposed to prolonged and increased pressures with daily activities and physiologic processes such as vaginal birth. The vagina changes in geometry over time under prolonged pressure, known as creep. Vaginal smooth muscle cells may contribute to creep. This may be critical for the function of vaginal and other soft tissues that experience fluctuations in their biomechanical environment. Therefore, the objective of this study was to develop methods to evaluate the contribution of smooth muscle to vaginal creep under multiaxial loading using extension - inflation tests. The vaginas from wildtype mice (C57BL/6 × 129SvEv; 3-6 months; n = 10) were stimulated with various concentrations of potassium chloride then subjected to the measured in vivo pressure (7 mmHg) for 100 s. In a different cohort of mice (n = 5), the vagina was stimulated with a single concentration of potassium chloride then subjected to 5 and 15 mmHg. A laser micrometer measured vaginal outer diameter in real-time. Immunofluorescence evaluated the expression of alpha-smooth muscle actin and myosin heavy chain in the vaginal muscularis (n = 6). When smooth muscle contraction was activated, vaginal creep behavior increased compared to the relaxed state. However, increased pressure decreased the active creep response. This study demonstrated that extension - inflation protocols can be used to evaluate smooth muscle contribution to the viscoelastic response of tubular soft tissues.
Topics: Female; Mice; Animals; Potassium Chloride; Mice, Inbred C57BL; Muscle, Smooth; Muscle Contraction; Vagina
PubMed: 36764168
DOI: 10.1016/j.jmbbm.2023.105702