Potassium Depletion Research Articles

Outdoor temperature and survival benefit of empiric potassium in users of furosemide in US Medicaid enrollees: a cohort study

ObjectiveHeat is associated with elevated all-cause mortality, and furosemide-induced potassium depletion might be worsened by heat-induced sweating. Because empiric potassium is associated with a marked survival benefit in users of...

Refeeding syndrome – Intensive care

Refeeding syndrome is a life-threatening condition resulting from over-rapid or unbalanced nutrition support given to malnourished patients. It usually occurs within 4 days of starting to feed. With starvation, levels of glucose begin to fall within 24–72 h. There is a resultant loss of body fat and protein and an accompanying depletion of potassium, phosphate, and magnesium.The reintroduction of nutrition to a starved or fasted individual results in a rapid decline in both gluconeogenesis and anaerobic metabolisms. The principle is to gradually step up the calories intake over a period of 3–5 days and at the same time keep a watch on electrolytes and continue with thiamine supplementation.

Metabolic Alkalosis

Metabolic alkalosis is a common clinical problem encountered by the nephrologist. An understanding of the pathogenesis of this electrolyte disorder, which includes a generative and a maintenance phase, is essential to elucidating the etiology and deciding on the appropriate treatment. Metabolic alkalosis is characterized by an increase in pH, a decrease in [H+], and an increase in [HCO3–]. The generative phase of metabolic alkalosis involves either loss of acid (e.g., gastrointestinal losses), gain of bicarbonate (e.g., antacids), or cellular shift (e.g., hypokalemia). The maintenance phase involves impairment of the renal handling of bicarbonate (decreased glomerular filtration, increased bicarbonate tubular reabsorption). We discuss the different etiologies, such as chloride depletion (e.g., vomiting), potassium depletion (e.g., primary hyperaldosteronism), and hypercalcemic states (e.g., milk-alkali syndrome). This review also discusses the symptoms, diagnosis, and prognosis of metabolic alkalosis. A diagnostic algorithm based on volume status and urine electrolytes will help differentiate the different etiologies. Treatment options are summarized based on chloride-sensitive or chloride-resistant metabolic alkalosis. This review contains 5 figures, 3 tables and 12 references Key words: chloride resistance, chloride sensitivity, generative phase, maintenance phase, metabolic alkalosis, syndromes with metabolic alkalosis

Adenosine Kinase couples sensing of cellular potassium depletion to purine metabolism

Adenosine Kinase (ADK) regulates the cellular levels of adenosine (ADO) by fine-tuning its metabolic clearance. The transfer of γ-phosphate from ATP to ADO by ADK involves regulation by the substrates and products, as well as by Mg2+ and inorganic phosphate. Here we present new crystal structures of mouse ADK (mADK) binary (mADK:ADO; 1.2 Å) and ternary (mADK:ADO:ADP; 1.8 Å) complexes. In accordance with the structural demonstration of ADO occupancy of the ATP binding site, kinetic studies confirmed a competitive model of auto-inhibition of ADK by ADO. In the ternary complex, a K+ ion is hexacoordinated between loops adjacent to the ATP binding site, where Asp310 connects the K+ coordination sphere to the ATP binding site through an anion hole structure. Nuclear Magnetic Resonance 2D 15N-1H HSQC experiments revealed that the binding of K+ perturbs Asp310 and residues of adjacent helices 14 and 15, engaging a transition to a catalytically productive structure. Consistent with the structural data, the mutants D310A and D310P are catalytically deficient and loose responsiveness to K+. Saturation Transfer Difference spectra of ATPγS provided evidence for an unfavorable interaction of the mADK D310P mutant for ATP. Reductions in K+ concentration diminish, whereas increases enhance the in vitro activity of mADK (maximum of 2.5-fold; apparent Kd = 10.4 mM). Mechanistically, K+ increases the catalytic turnover (Kcat) but does not affect the affinity of mADK for ADO or ATP. Depletion of intracellular K+ inhibited, while its restoration was accompanied by a full recovery of cellular ADK activity. Together, this novel dataset reveals the molecular basis of the allosteric activation of ADK by K+ and highlights the role of ADK in connecting depletion of intracellular K+ to the regulation of purine metabolism.

Streptococcus mutans activates the AIM2, NLRP3 and NLRC4 inflammasomes in human THP-1 macrophages

Streptococcus mutans (S. mutans), a major aetiologic agent of dental caries, is involved in systemic diseases, such as bacterial endocarditis, if it enters the bloodstream through temporary bacteraemia. Interleukin (IL)-1β, a proinflammatory cytokine, is related to the host defences against pathogens, and its synthesis, maturation, and secretion are tightly regulated by the activation of the inflammasome, an inflammatory signalling complex. This study examined the signalling mechanism of IL-1β secretion and the inflammasome pathway induced by S. mutans to explain the molecular mechanism through which systemic infection by oral streptococci can occur. After infection of THP-1 cells with S. mutans, the expression of inflammasome components was detected using various methods. S. mutans induced IL-1β secretion via caspase-1 activation, and S. mutans-induced IL-1β secretion required absent in melanoma (AIM2), NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing 4 (NLRC4) inflammasome activation. In particular, the S. mutans-induced NLRP3 inflammasome was mediated by adenosine triphosphate (ATP) release, potassium depletion and lysosomal damage. Our study provides novel insight into the innate immune response against S. mutans infection.

Environmental sustainability of corn (Zea mays L.) production on the basis of nitrogen fertilizer application: The case of Lahijan, Iran

A field experiment was conducted in Lahijan, Iran to determine the environmental impact of four corn (Zea mays L.) genotypes production under three nitrogen (N) fertilizer application rates using the life cycle assessment (LCA) methodology. Treatments consisted of three N levels (300, 400, and 500 kg ha−1 of urea) and four corn genotypes (KSC 647, KSC 700, KSC 704, and a local variety). Six impact categories, i.e., global warming, acidification, terrestrial eutrophication, depletion of fossil resources, depletion of potassium resources and depletion of phosphate resources, were determined. There was an increasing trend in grain yield with increasing N rate from 300 to 400 kg ha−1, but further increase in N rate (500 kg ha−1) was not beneficial for all genotypes. The highest grain yield (14.49 t ha−1) was observed for the hybrid KSC 647. The maximum values of environmental index (1.53) and resources depletion index (1.11) were determined in the production of one tonne of grain yield for the local corn variety treated with 500 kg ha−1 of urea. The production of one tonne of grain yield by the hybrid KSC 647 treated with 300 kg ha−1 of urea emitted the least amounts of NH3, N2O, NOX, CO2, CH4, and SO2 (2.158, 0.368, 0.449, 64.510, 0.090, and 0.115 kg per tonne of grain yield of corn, respectively). The selection of superior genotypes in terms of grain yield and low N consumption showed lower damage to the environment. The use of high-yielding genotypes increases productivity and alleviates the environmental impact of production.

Potassium Supplying Capacity of Diverse Soils and K-Use Efficiency of Maize in South Asia

Increased nutrient withdrawal by rapidly expanding intensive cropping systems, in combination with imbalanced fertilization, is leading to potassium (K) depletion from agricultural soils in Asia. There is an urgent need to better understand the soil K-supplying capacity and K-use efficiency of crops to address this issue. Maize is increasingly being grown in rice-based systems in South Asia, particularly in Bangladesh and North East India. The high nutrient extraction, especially K, however, causes concerns for the sustainability of maize production systems in the region. The present study was designed to estimate, through a plant-based method, the magnitude, and variation in K-supplying capacity of a range of soils from the maize-growing areas and the K-use efficiency of maize in Bangladesh. Eighteen diverse soils were collected from several upazillas (or sub-districts) under 11 agro-ecological zones to examine their K-supplying capacity from the soil reserves and from K fertilization (100 mg K kg−1 soil) for successive seven maize crops grown up to V10–V12 in pots inside a net house. A validation field experiment was conducted with five levels of K (0, 40, 80, 120 and 160 kg ha−1) and two fertilizer recommendations based on “Nutrient Expert for Maize-NEM” and “Maize Crop Manager-MCM” decision support tools (DSSs) in 12 farmers’ fields in Rangpur, Rajshahi and Comilla districts in Bangladesh. Grain yield and yield attributes of maize responded significantly (p < 0.001) to K fertilizer, with grain yield increase from 18 to 79% over control in all locations. Total K uptake by plants not receiving K fertilizer, considered as potential K-supplying capacity of the soil in the pot experiment, followed the order: Modhukhali > Mithapukur > Rangpur Sadar > Dinajpur Sadar > Jhinaidah Sadar > Gangachara > Binerpota > Tarash > Gopalpur > Daudkandi > Paba > Modhupur > Nawabganj Sadar > Shibganj > Birganj > Godagari > Barura > Durgapur. Likewise, in the validation field experiment, the K-supplying capacity of soils was 83.5, 60.5 and 57.2 kg ha−1 in Rangpur, Rajshahi, and Comilla, respectively. Further, the order of K-supplying capacity for three sites was similar to the results from pot study confirming the applicability of results to other soils and maize-growing areas in Bangladesh and similar soils and areas across South Asia. Based on the results from pot and field experiments, we conclude that the site-specific K management using the fertilizer DSSs can be the better and more efficient K management strategy for maize.

Double trouble: managing diabetic emergencies in patients with heart failure

Double trouble: managing diabetic emergencies in patients with heart failure

Depletion of potassium and sodium in mantles of Mars, Moon and Vesta by core formation

The depletions of potassium (K) and sodium (Na) in samples from planetary interiors have long been considered as primary evidence for their volatile behavior during planetary formation processes. Here, we use high-pressure experiments combined with laser ablation analyses to measure the sulfide-silicate and metal-silicate partitioning of K and Na at high pressure (P) – temperature (T) and find that their partitioning into metal strongly increases with temperature. Results indicate that the observed Vestan and Martian mantle K and Na depletions can reflect sequestration into their sulfur-rich cores in addition to their volatility during formation of Mars and Vesta. This suggests that alkali depletions are not affected solely by incomplete condensation or partial volatilization during planetary formation and differentiation, but additionally or even primarily reflect the thermal and chemical conditions during core formation. Core sequestration is also significant for the Moon, but lunar mantle depletions of K and Na cannot be reconciled by core formation only. This supports the hypothesis that measured isotopic fractionations of K in lunar samples represent incomplete condensation or extensive volatile loss during the Moon-forming giant impact.

Metabolic stress directs WNK kinases to aggresomes for pooling and degradation in the distal convoluted tubule of the kidney

ObjectiveRenal salt retention due to excessive function of the renal NaCl cotransporter (NCC) along the distal convoluted tubule (DCT) plays a central role in the pathogenesis of hypertension. The Western type diet with high salt and low potassium content (HS/LK) has been shown to increase NCC activity by stimulating its phosphorylation via a kinase cascade comprising with‐no‐lysine kinases (WNKs) and a Ste20‐related kinase (SPAK). WNKs and SPAK have been shown to accumulate in perinuclear aggregates in response to potassium depletion, but the functional significance of these aggregates remained obscure. These structures may in part reflect a degradative pathway but may serve pooling functions as well.MethodsMice received HS/LK or control diets for 10 days. WNK1‐transfected DCT cells were exposed to vehicle, hyperosmotic stress, or potassium depletion. WNK1, WNK4, SPAK, phospho‐S383 SPAK, and various autophagy markers were studied by immunofluorescence and immunoblotting. Electron microscopy was applied for ultrastructural analysis.ResultsHS/LK diet induced accumulation of WNKs and SPAK in the form of perinuclear protein aggregates within DCT cells. These aggregates were rare in DCT of mice treated with control diet and virtually absent after administration of high potassium diet. The autophagy marker ATG5 was present in the aggregates and the 20S proteasome signal was intensified adjacently, whereas standard lysosomal markers showed no significant association with the punctate WNK/SPAK signal. Ultrastructural analysis of DCT in kidneys of mice treated with HS/LK revealed abundant aggresomes adjacent to rough endoplasmic reticulum and clathrin‐coated vesicles. Evaluation of cultured DCT cells transfected with WNK1 or KS‐WNK1 revealed formation of similar aggresomes in response to potassium depletion, whereas hyperosmotic stress induced formation of autophagosomes. Pretreatment of cells with proteasome inhibitor MG‐132 or autophagy/lysosome inhibitor bafilomycin A1 prior to potassium depletion substantially augmented the size of WNK1‐containing aggresomes.ConclusionChallenging of DCT epithelium induces the formation of perinuclear aggresomes which pool the components of the kinase cascade controlling NCC activity. From there, WNKs and SPAK may either be degraded via proteasomes or lysosomes, or reintroduced into the signal chain.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fulminant type 1 diabetes mellitus: a case report

Type 1 diabetes mellitus is a metabolic disease caused by insulin deficiency that results from destruction of β-cells in the pancreas. Based on American Diabetes Association, there are two types of type 1 diabetes mellitus: type 1A (autoimmune) and 1B (idiopathic). In this case, we are presenting a new archetype of type 1 diabetes named fulminant type 1 diabetes mellitus. This disease results from quick destruction of β-cells byanautoimmune mechanism. The manifestation of this disease consists of unspecific flu-like symptoms, abdominal symptoms, to specific hyperglycemia symptoms such as fatigue, malaise, change in mental status that are attributable to high blood glucose and ketosis. Laboratory examination reveals high blood glucose, normal glycosylated hemoglobin, ketosis or ketoacidosis, potassium depletion and elevation of liver function tests. Treatment consists of intravenous infusion followed by insulin injection for blood glucose control, followed by treatment of metabolic derangements such as acid-base and electrolyte disorder.

Estimation of potasium reserves in zonal chernozemic soils of Ukraine's forest-steppe

In the soil cover of the forest-steppe zone, typical chernozems, which occupy almost 50% of the total area of arable lands that are insufficiently fertilized with organics and minerals, prevail. Our task was to investigate the potassium content in these soils in order to gain insight into its reserves and availability for agricultural plants. For this purpose, soils of this type of different granulometric texture were investigated. The content of the fine-dispersed fraction of typical chernozems, total potassium in this fraction and in the soil as a whole is determined. Indicators on the genetic horizons were researched there. The content of hydromicaceous minerals as the most available potassium reserves of plants nutrition is shown. The reserves of potassium (after Gorbunov) in one meter-deep layer of investigated soils are calculated. All investigated soils have the same specificity of the reserves distribution in the horizons due to the common genesis processes and the same parent materials. The illuvium horizon of podzolized chernozem entraps a certain part of silt and potassium that is explained by the specifics of the formation of this horizon. Near reserve of chernozem soils contains less than 50% of potassium from the general reserve that suggests the potassium depletion of chernozems.

Assessment of Soil Nutrients Limiting Sustainable Potato Production in the Highlands of South-Western Uganda

Soil fertility management is one of the major strategies for improving potato productivity in the highlands of south-western Uganda. Land belonging to potato farmers is highly fragmented hindering sustainable potato production under small-holder farming systems. Land fragmentation brings a major challenge to small-scale farmers in soil fertility management, increasing costs of production. However, identifying major soil nutrients limiting potato production in the highlands of south-western Uganda is an avenue of applying appropriate soil nutrients to improve potato productivity without degrading the soils. It also assists farmers in investing in the necessary soil nutrients and, hence reducing the costs of production while improving potato productivity. The study indicated that soil potassium was the most single significant soil nutrient limiting potato productivity especially in the fields located on hilltops and far from homesteads. Hence, it was imperative that farmers apply potassium containing fertilizers to minimize potassium depletion but also increase potato productivity. It was also important for farmers to always integrate disease management with soil nutrient management for improved potato productivity.

Metabolic Alkalosis

Metabolic alkalosis is a common clinical problem encountered by the nephrologist. An understanding of the pathogenesis of this electrolyte disorder, which includes a generative and a maintenance phase, is essential to elucidating the etiology and deciding on the appropriate treatment. Metabolic alkalosis is characterized by an increase in pH, a decrease in [H+], and an increase in [HCO3–]. The generative phase of metabolic alkalosis involves either loss of acid (e.g., gastrointestinal losses), gain of bicarbonate (e.g., antacids), or cellular shift (e.g., hypokalemia). The maintenance phase involves impairment of the renal handling of bicarbonate (decreased glomerular filtration, increased bicarbonate tubular reabsorption). We discuss the different etiologies, such as chloride depletion (e.g., vomiting), potassium depletion (e.g., primary hyperaldosteronism), and hypercalcemic states (e.g., milk-alkali syndrome). This review also discusses the symptoms, diagnosis, and prognosis of metabolic alkalosis. A diagnostic algorithm based on volume status and urine electrolytes will help differentiate the different etiologies. Treatment options are summarized based on chloride-sensitive or chloride-resistant metabolic alkalosis. This review contains 5 figures, 3 tables and 12 references Key words: chloride resistance, chloride sensitivity, generative phase, maintenance phase, metabolic alkalosis, syndromes with metabolic alkalosis

EXOGENOUS C16 CERAMIDE ALTERS TRANSFERRIN ENDOCYTOSIS AND RECYCLING KINETICS IN HUMAN T-LYMPHOMA JURKAT CELL LINE

In the present study, we investigated the role of exogenous long chain ceramide (C16 cer) in transferrin (Tf) internalization and recycling pathways in jurkat human T lymphoma cell line. We traced fluorescently labeled Tf cellular entry, Tf nucleation (Tfn) and recycling and determined the time frame for each step. Clathrin dependent pathway inhibition was carried out by two different means; potassium depletion and chlorpromazine (CPZ) to investigate the entry pathway after treatment with C16 cer. The level of transferrin receptor (TfR), clathrin and cleaved caspase 3 were carried out by Western blot. There were obvious differences between control and C16 cer treated cells in the kinetics of Tf up taking and recycling. Formation of Tfn in C16 cer treated cells was different in time, size and shape compared with control cells. Also, results indicated that C16 cer changed the Tf internalization pathway to become clathrin independent pathway. This mis-internalization of Tf leads to loss of cell viability and finally apoptotic cell death. The current obtained data may be applicable for clathrin dependent machinery used by different receptors and agents.

Impact of cropping intensity on soil properties and plant available nutrients in hot arid environment of North-Western India

ABSTRACTIn order to maintain crop productivity in arid western plain of India, there is a need for understanding the nutrient supplying capacity of soil, which poses many challenges for crop production. We studied four different levels of crop intensification, namely barren land, low, medium and high crop intensity and assessed their impact on soil properties and available nutrients. High intensity showed higher accumulation of available-nitrogen (N) and phosphorus (P) in the 0–15 cm depth and then decreased with increasing depths. Higher depletion of available potassium (K) in the surface layer was observed in medium and high cropping intensities. Data indicated that the crop intensification led to an increase in availability of micronutrients. Changes in soil pH and calcium carbonate (CaCO3) had strong influence on the distribution of micronutrients. A highly significant correlation coefficient between available nutrients and organic carbon showed that soil organic matter is the main governing factor for sustainable crop production in arid environment.

English

English

Electrolyte and Acid-Base Disturbances in End-Stage Liver Disease: A Physiopathological Approach.

Electrolyte and acid-base disturbances are frequent in patients with end-stage liver disease; the underlying physiopathological mechanisms are often complex and represent a diagnostic and therapeutic challenge to the physician. Usually, these disorders do not develop in compensated cirrhotic patients, but with the onset of the classic complications of cirrhosis such as ascites, renal failure, spontaneous bacterial peritonitis and variceal bleeding, multiple electrolyte, and acid-base disturbances emerge. Hyponatremia parallels ascites formation and is a well-known trigger of hepatic encephalopathy; its management in this particular population poses a risky challenge due to the high susceptibility of cirrhotic patients to osmotic demyelination. Hypokalemia is common in the setting of cirrhosis: multiple potassium wasting mechanisms both inherent to the disease and resulting from its management make these patients particularly susceptible to potassium depletion even in the setting of normokalemia. Acid-base disturbances range from classical respiratory alkalosis to high anion gap metabolic acidosis, almost comprising the full acid-base spectrum. Because most electrolyte and acid-base disturbances are managed in terms of their underlying trigger factors, a systematic physiopathological approach to their diagnosis and treatment is required.

Adaptation to potassium depletion in human : role of progesterone ?

In this study, we examined whether reduction in the intake of K+ induce lasting changes in the plasma concentration of circulating steroids. We have previously shown that plasma progesterone (PG) levels specifically increases in response to chronic and sustained K+ depletion in male and female mice. In this physiological context, progesterone regulates renal K+ handling by stimulating the expression of H,K‐ATPase type 2 (HKA2) through a RU486 (PG receptor antagonist)‐sensitive pathway. The human adrenal steroidogenesis strongly differs from rodents because of the presence of a CYP17 activity that metabolizes PG into 17‐OH PG and may prevent its accumulation and release in the plasma. To address the role of PG in renal adaptation to K depletion in human, we designed a cross‐over protocol in which healthy subjects were submitted to a 7‐days K+ depleted diet in the absence (placebo period) or presence of a PG antagonist (RU486 period). We studied their renal adaptation to K+ depletion and the induced changes in plasma adrenal steroids concentrations before and 1h after stimulation by ACTH (SYNACTHENE®). Since this adaptation could be relevant in the case of severe and chronic renal hypokalemia, plasma adrenal steroids were measured in patients with chronic severe renal hypokalemia related to a congenital salt losing tubulopathy, the Gitelman syndrome.During the two periods, a week of reduction of dietary K+ intake induced both daily urinary excretion of K+ and fractional excretion of K+ decreased by a factor 2, without affecting daily urinary excretion or fractional excretion of Na+. Under placebo condition, plasma K+ concentration decreased by 0.3 ± 0.1 mmol/l (p= 0.0180) and subjects became slightly hypokalemic, without change in plasma concentrations of sodium, chloride, bicarbonate or creatinine. As expected, plasma aldosterone decreased by 55% and more surprisingly, DHEA decreased by 20% but the other steroids concentration (Cortisol, PG, 17‐OH PG, deoxycorticosterone, delat4‐androstenedione) are not modified neither under basal or after SYNACTHENE® treatment. Under RU486 treatment, the decrease of the plasma K+ level is much faster than under placebo and the plasma aldosterone concentration is decreased even more than under the placebo period indicating that RU486 interferes with the regulation of the K+ balance. The basal level of steroids is similar in Gitelman patients compared to healthy volunteers. However, the stimulation of adrenal steroidogenesis by SYNACTHENE® induces a stronger rise of PG, 17‐OH PG and delta4‐androstenedione indicating that in Gitelman patients the 3bHSD activity is stimulated but not activated.Altogether, these results indicate that, in men, a moderate reduction of the K+ intake does not result in a visible rise of plasma PG but the effect of RU486 and the putative stimulation of the adrenal 3bHSD‐dependent steps in Gitelman patients may indicate that this hormonal system may be relevant in the regulation of K+ balance.Support or Funding InformationThe DRIVING trial was supported by research grants from the French Ministry of Health (CRC 2012 grant # CRC12122)

Renal Tubular Ubiquitin-Protein Ligase NEDD4-2 Is Required for Renal Adaptation during Long-Term Potassium Depletion.

Adaptation of the organism to potassium (K+) deficiency requires precise coordination among organs involved in K+ homeostasis, including muscle, liver, and kidney. How the latter performs functional and molecular changes to ensure K+ retention is not well understood. Here, we investigated the role of ubiquitin-protein ligase NEDD4-2, which negatively regulates the epithelial sodium channel (ENaC), Na+/Cl- cotransporter (NCC), and with no-lysine-kinase 1 (WNK1). After dietary K+ restriction for 2 weeks, compared with control littermates, inducible renal tubular NEDD4-2 knockout (Nedd4LPax8/LC1 ) mice exhibited severe hypokalemia and urinary K+ wasting. Notably, expression of the ROMK K+ channel did not change in the distal convoluted tubule and decreased slightly in the cortical/medullary collecting duct, whereas BK channel abundance increased in principal cells of the connecting tubule/collecting ducts. However, K+ restriction also enhanced ENaC expression in Nedd4LPax8/LC1 mice, and treatment with the ENaC inhibitor, benzamil, reversed excessive K+ wasting. Moreover, K+ restriction increased WNK1 and WNK4 expression and enhanced SPAK-mediated NCC phosphorylation in Nedd4LPax8/LC1 mice, with no change in total NCC. We propose a mechanism in which NEDD4-2 deficiency exacerbates hypokalemia during dietary K+ restriction primarily through direct upregulation of ENaC, whereas increased BK channel expression has a less significant role. These changes outweigh the compensatory antikaliuretic effects of diminished ROMK expression, increased NCC phosphorylation, and enhanced WNK pathway activity in the distal convoluted tubule. Thus, NEDD4-2 has a crucial role in K+ conservation through direct and indirect effects on ENaC, distal nephron K+ channels, and WNK signaling.