Potassium deficiency decreases the capacity for urea synthesis and markedly increases ammonia in rats.

Our study provides novel findings of experimental hypokalemia reducing urea cycle functionality and thereby severely increasing plasma ammonia. This is pathophysiologically interesting because plasma ammonia increases during hypokalemia by a hitherto unknown mechanism, which may be particular important in relation to the unexplained link between hypokalemia and hepatic encephalopathy. Potassium deficiency decreases gene expression, protein synthesis, and growth. The urea cycle maintains body nitrogen homeostasis including removal of toxic ammonia. Hyperammonemia is an obligatory trait of liver failure, increasing the risk for hepatic encephalopathy, and hypokalemia is reported to increase ammonia. We aimed to clarify the effects of experimental hypokalemia on the in vivo capacity of the urea cycle, on the genes of the enzymes involved, and on ammonia concentrations. Female Wistar rats were fed a potassium-free diet for 13 days. Half of the rats were then potassium repleted. Both groups were compared with pair- and free-fed controls. The following were measured: in vivo capacity of urea-nitrogen synthesis (CUNS); gene expression (mRNA) of urea cycle enzymes; plasma potassium, sodium, and ammonia; intracellular potassium, sodium, and magnesium in liver, kidney, and muscle tissues; and liver sodium/potassium pumps. Liver histology was assessed. The diet induced hypokalemia of 1.9 ± 0.4 mmol/L. Compared with pair-fed controls, the in vivo CUNS was reduced by 34% (P < 0.01), gene expression of argininosuccinate synthetase 1 (ASS1) was decreased by 33% (P < 0.05), and plasma ammonia concentrations were eightfold elevated (P < 0.001). Kidney and muscle tissue potassium contents were markedly decreased but unchanged in liver tissue. Protein expressions of liver sodium/potassium pumps were unchanged. Repletion of potassium reverted all the changes. Hypokalemia decreased the capacity for urea synthesis via gene effects. The intervention led to marked hyperammonemia, quantitatively explainable by the compromised urea cycle. Our findings motivate clinical studies of patients with liver disease.

Rise in Potassium Deficiency in the US Population Linked to Agriculture Practices and Dietary Potassium Deficits.

This paper, for the first time, provides evidence that current practices that lead to agricultural crop removal of potassium are unsustainable and likely contributed to the decline in dietary potassium intake and rise in hypokalemia prevalence in the US population. Potassium concentrations in beef, pork, turkey, fruit, vegetables, cereal crops, and so forth decreased between 1999 and 2015 based on the examination of potassium values of food items of USDA standard reference. Ratios of potassium input to removal by crops between 1987 and 2014, potassium in topsoil, and crop-available soil potassium in US farms all declined in recent years. Reported reductions in dietary potassium intake correspond to these decreases in the food supply and to increases in hypokalemia prevalence in the US population. Results of this paper provide new understanding on links between potassium management in agricultural practices and potassium intake deficits, which is needed for combating increasing hypokalemia prevalence in the US population.

Risk of respiratory failure among hospitalized patients with various admission serum potassium levels.

BACKGROUND: The objective of this study was to assess the relationship between admission serum potassium and the risk of respiratory failure requiring mechanical ventilation in all hospitalized patients. METHODS: All non-dialysis and non-mechanically ventilated patients who had serum potassium measurement at admission from 2011 to 2013 were studied. Serum potassium levels were stratified into five groups; ≤3.4, 3.5 to 3.9, 4.0 to 4.4, 4.5 to 4.9, 5.0 to 5.4, and ≥5.5 mEq/L. The outcome of interest was the respiratory failure requiring mechanical ventilation during hospitalization. Logistic regression analysis was performed to assess the independent risk of in-hospital respiratory failure requiring mechanical ventilation based on various admission serum potassium, using serum potassium of 4.0 to 4.4 mEq/L as the reference group. RESULTS: Of 67,034 eligible patients, with the mean admission serum potassium of 4.2 ± 0.5 mEq/L, 2,886 (4.3%) patients developed respiratory failure requiring mechanical ventilation during hospitalization. As demonstrated by U-shaped association, increased risk of in-hospital respiratory failure was significantly associated with low admission serum potassium ≤ 3.4 mEq/L (odds ratio 1.36, p-value <0.001) and high admission serum potassium ≥5.5 mEq/L (odds ratio 1.37, p-value = 0.01). CONCLUSION: Increased risk of in-hospital respiratory failure requiring mechanical ventilation was noted when serum potassium was below 3.5 mEq/L or above 5.4 mEq/L at the time of hospital admission. Patients with either hypokalemia or hyperkalemia are at risk of respiratory failure requiring mechanical ventilation.

Effects of potassium supplements on glucose metabolism in African Americans with prediabetes: a pilot trial.

Background: Low potassium has been identified both as a risk factor for type 2 diabetes and as a mediator of the racial disparity in diabetes risk. Low potassium could be a potentially modifiable risk factor, particularly for African Americans.Objective: We sought to determine the effects of potassium chloride (KCl) supplements, at a commonly prescribed dose, on measures of potassium and glucose metabolism.Design: Among African-American adults with prediabetes, we conducted a double-blinded pilot randomized controlled trial that compared the effects of 40 mEq K/d as KCl supplements with a matching placebo, taken for 3 mo, on measures of potassium and glucose metabolism, with measures collected from frequently sampled oral-glucose-tolerance tests (OGTTs).Results: Twenty-seven of 29 recruited participants completed the trial. Participants had high adherence to the study medication (92% by pill count). Participants in both groups gained weight, with an overall mean ± SD weight gain of 1.24 ± 2.03 kg. In comparison with participants who received placebo, urine potassium but not serum potassium increased significantly among participants randomly assigned to receive KCl (P = 0.005 and 0.258, respectively). At the end of the study, participants taking KCl had stable or improved fasting glucose, with a mean ± SD change in fasting glucose of -1.1 ± 8.4 mg/dL compared with an increase of 6.1 ± 7.6 mg/dL in those who received placebo (P = 0.03 for comparison between arms). There were no significant differences in glucose or insulin measures during the OGTT between the 2 groups, but there was a trend for improved insulin sensitivity in potassium-treated participants.Conclusions: In this pilot trial, KCl at a dose of 40 mEq/d did not increase serum potassium significantly. However, despite weight gain, KCl prevented worsening of fasting glucose. Further studies in larger sample sizes, as well as with interventions to increase serum potassium more than was achieved with our intervention, are indicated to definitively test this potentially safe and inexpensive approach to reducing diabetes risk. This trial was registered at clinicaltrials.gov as NCT02236598.

Does Potassium Deficiency Contribute to Hypertension in Children and Adolescents?

The increasing prevalence of cardiovascular risk factors in children and adolescents has been largely, but not entirely, related to the childhood obesity epidemic. Among the noted risk factors detectable in children is elevated blood pressure. Emerging findings indicate that in addition to overweight and obesity, sodium intake is associated with elevated blood pressure in youth. Moreover, dietary sodium intake is quite high and well above recommended levels throughout childhood. In adults, the relationship of sodium consumption with hypertension is well established, and there is evidence from both population and clinical studies that potassium intake is also associated with blood pressure. Higher potassium intake is associated with lower blood pressure; and potassium deficit leads to an increase in blood pressure. Findings on relationships of potassium intake with blood pressure in childhood are sparse. There are some reports that provide evidence that a dietary pattern that includes potassium-rich foods is associated with lower blood pressure and may also lower blood pressure in adolescents with elevated blood pressure. Considering the secular changes in dietary patterns throughout childhood, it is prudent to encourage a diet for children that is high in potassium-rich foods.

An infectious cause of acute kidney injury with low serum potassium.

A 67-year-old man was referred to our hospital because of acute kidney injury, thrombocytopenia and hyperbilirubinemia. Despite severe kidney failure, hypokalemia was present. One infectious cause explained the whole clinical picture.

Sodium surfeit and potassium deficit: keys to the pathogenesis of hypertension.

The pathogenic role of Na(+) in primary hypertension is widely recognized but that of K(+) remains unappreciated. Yet, extensive evidence indicates that together, the body's dominant cations constitute the chief environmental factor in the pathogenesis of hypertension and its cardiovascular sequelae. In this Review, we provide a synthesis of the determinants of Na(+) retention and K(+) loss developing in the body as the Na(+)-rich and K(+)-poor modern diet interacts with kidneys intrinsically poised to conserve Na(+) and excrete K(+); and the molecular pathways utilized by these disturbances in the central nervous system and the periphery to increase sympathetic tone and vascular resistance, and establish hypertension. These fresh insights point to new directions for targeted pharmacotherapy of hypertension. The interdependency of Na(+) and K(+) in the pathogenesis of hypertension indicates that Na(+) restriction and increased K(+) intake are important strategies for the primary prevention and treatment of hypertension and its cardiovascular consequences.

Excess dietary sodium and inadequate potassium intake in Italy: results of the MINISAL study.

OBJECTIVE: As excess sodium and inadequate potassium intake are causally related to hypertension and cardiovascular disease, the MINISAL-GIRCSI Program aimed to provide reliable estimates of dietary sodium and potassium intake in representative samples of the Italian population. DESIGN AND METHODS: Random samples of adult population were collected from 12 Italian regions, including 1168 men and 1112 women aged 35-79 yrs. Electrolyte intake was estimated from 24 hour urine collections and creatinine was measured to estimate the accuracy of the collection. Anthropometric indices were measured with standardised procedures. RESULTS: The average sodium excretion was 189 mmol (or 10.9 g of salt/day) among men and 147 mmol (or 8.5 g) among women (range 27-472 and 36-471 mmol, respectively). Ninety-seven % of men and 87% of women had a consumption higher than the WHO recommended target of 5g/day. The 24 h average potassium excretion was 63 and 55 mmol, respectively (range 17-171 and 20-126 mmol), 96% of men and 99% of women having an intake lower than 100 mmol/day (European and American guideline recommendation). The mean sodium/potassium ratio was 3.1 and 2.8 respectively, i.e. over threefold greater than the desirable level of 0.85. The highest sodium intake was observed in Southern regions. Sodium and potassium excretion were both progressively higher the higher the BMI (p < 0.0001). CONCLUSIONS: These MINISAL preliminary results indicate that in all the Italian regions thus far surveyed dietary sodium intake was largely higher and potassium intake lower than the recommended intakes. They also highlight the critical association between overweight and excess salt intake.

Protection against ß adrenoceptor agonist reduction of plasma potassium in severe but not in moderate hypokalemia.

K-depleted and control rats were anesthetized and infused with terbutalin. In controls, plasma K concentration (pK) decreased by 0.7 mm (P = 0.01). In moderate hypokalemia terbutalin-induced decrease in pK was reduced by 0.3 mm for each 1 mm decrease in pK (n = 8, R(2) = 0.82, P = 0.002) and by 0.2 mm for each 10 mmol/g wet wt. decrease in muscle K content (n = 8, R(2) = 0.66, P = 0.01). Hence, for baseline pK of 4, 3 and 2 mm, decrease in pK was 0.7, 0.4 and 0.1 mm, respectively. In severe hypokalemia (1.7 mm), terbutain induced no further reduction in pK. The combined infusion of insulin and terbutalin showed no additive effect. Normalization of pK by KCl infusion in severe hypokalemia immediately abolished protection against terbutalin induced further pK reduction. Hence, terbutalin clamped pK at around 4 mm, whereas it continued to increase to around 5 mm without terbutalin infusion. Major new findings are: Protection against terbutalin induced further reduction in pK in severe pre-existing hypokalemia (<2 mm) and blunted but nevertheless severe further reduction in pK in more moderate pre-existing hypokalemia; immediate abolishment of protection by normalization of pK; protection against additive reduction in pK by terbutalin and insulin in severe hypokalemia. It may be advisable to avoid hypokalemia when using ß adrenoceptor agonists and to maintain pK in the upper normal range if at the risk of arrhythmia.

Decrease in dietary K intake stimulates the generation of superoxide anions in the kidney and inhibits K secretory channels in the CCD.

We previously demonstrated that K depletion inhibited ROMK-like small-conductance K channels (SK) in the cortical collecting duct (CCD) and that the effect was mediated by superoxide anions that stimulated Src family protein tyrosine kinase (PTK) and mitogen-activated protein kinase (MAPK) (51). However, because animals on a K-deficient diet had a severe hypokalemia, superoxide-dependent signaling may not regulate ROMK channels under physiological conditions with a normal plasma K concentration. In the present study, we used the patch-clamp technique and Western blot to examine the effect of a moderate K restriction on ROMK-like SK channels and the role of PTK and MAPK in regulating apical K channels in the CCD of animals on a low-K diet (LK; 0.1% K). Rats and mice fed a LK diet for 7 days had a normal plasma K concentration. However, a LK intake increased the expression of angiotensin II type 1 receptor in the kidney. Moreover, patch-clamp experiments demonstrated that LK intake decreased the probability finding SK channels and channel activity defined by NP(o) (a product of channel number and open probability) in the CCD of both rat and mouse kidneys. Also, LK intake significantly stimulated the production of superoxide anions in the renal cortex and outer medulla in both rats and mice and increased superoxide level in the rat CCD. Moreover, LK intake augments the phosphorylation of p38 and ERK MAPK, the expression of c-Src and tyrosine phosphorylation of ROMK channels. However, treatment of animals with tempol abolished the effect of LK intake on MAPK and c-Src and increased ROMK channel activity in comparing with those of nontreated rats on a LK diet. Inhibiting p38 and ERK with SB202190 and PD98059 significantly stimulated SK in the CCD in rats on a LK diet. In addition, inhibition of PTK with herbimycin A activated SK channels in the CCD from rats on a LK diet. We conclude that LK intake stimulates the generation of superoxide anion and related products and that MAPK and Src family PTK play a physiological role in inhibiting apical K channels in the principal cells in response to LK intake.

Diuretic-induced potassium depletion and glucose intolerance are not related to hyperactivity of the renin-angiotensin-aldosterone system in hypertensive patients with the metabolic syndrome.

The metabolic syndrome (MS) has been associated with hyperactivity of the renin-angiotensin-aldosterone system (RAAS). To assess the hypothesis that diuretic therapy in MS patients through further stimulation of RAAS would elicit greater potassium (K) depletion, two groups of hypertensive patients with (MS group [MSG]; n=20) and without (control group [CG]; n=19) MS were studied. Plasma renin activity (PRA), aldosterone (PA), and K levels were determined and an oral glucose tolerance test with plasma insulin determinations for calculation of homeostasis model assessment of insulin resistance (HOMA-IR), sensitivity (ISI), and secretion (HOMA-beta) was performed, both before and 12 weeks after hydrochlorothiazide (HCT; 25 mg/d) therapy. At baseline, higher HOMA IR and HOMA-beta and lower ISI and plasma K were found in the MSG than in the CG, with no differences in PA and PRA between groups. With therapy, PRA increased similarly in both groups while PA increased only in the MSG. However, greater reduction in plasma K occurred in the CG, and the 2 groups reached similar final K values. Impairment in glucose tolerance occurred in both groups, with no change in HOMA-beta in the CG and reduction in the MSG, suggesting that diuretic therapy increases insulin resistance and impairs insulin secretion independent of abdominal obesity. These alterations could not be attributed to hyperactivity of RAAS.

Calcium, magnesium, potassium and sodium intakes in Japanese children aged 3 to 5 years.

The present study aimed to evaluate in preschool children the intakes of Ca, Mg that possibly affect health and tooth formation and the intakes of K and Na that may affect lifestyle-related diseases. Information on dietary intake was collected from 90 preschool children (15 boys and 15 girls each in the 3-, 4- and 5-year old groups) on 3 separate days in the school fiscal year 1999 (April 1999 to March 2000) by the duplicate-diet technique. The Ca, Mg, K, and Na concentrations were determined by atomic absorption spectrometry using wet-ashed samples. The medians of mean daily intakes of Ca, Mg, K and Na in 3- to 5-year-old children were 432 mg, 110 mg, 1.18 g and 1.60 g, respectively, and no significant differences with regard to gender were observed. Seasonal varia-tion of intake was seen for each mineral. Calcium intake in most preschool children did not meet adequate intake (AI), probably due to low intakes of milk and dairy products in Japan. Magnesium intake was below the estimated average requirement (EAR) in 13.3% of the subjects, while the K intake met the AI. Sodium intake in a quarter of preschool children exceeded the tentative dietary goal. We concluded that in Japanese children aged 3-5 years; Ca intake is low, Na intake is high, and K intake is adequate, but some children could be at risk for Mg deficiency.

Effects of hydration with salt repletion on renal toxicity of conventional amphotericin B empirical therapy: a prospective study in patients with hematological malignancies.

OBJECTIVE: Several studies have suggested that hydration and sodium load might reduce nephrotoxicity related to amphotericin B-deoxycholate (AmB-d). However, a schedule of these nephroprotective measures has not been standardized until now. A protocol of hydration and electrolyte supplementation was used prospectively in patients with hematological malignancies receiving empirical AmB-d treatment to evaluate its effect on AmB-d-related renal toxicity. PATIENTS AND METHODS: A total of 77 consecutive patients received AmB-d (1 mg/kg per day) in association with an initial intravenous hydration of at least 1 l/m2 body surface, containing at least 1 l of 0.9% saline daily. Hydration was increased when serum creatinine levels showed a 20% increase from baseline. Serum electrolytes were replaced when indicated. RESULTS: The median duration of AmB-d therapy was 14 days. The mean intravenous hydration and the mean diuresis were 1530 and 1970 ml/m2 of body surface per day, respectively. Overall, 55 patients (71.4%) received a mean of 18.5 days of therapy without dose-limiting adverse events. Despite significant increases in mean creatinine serum levels and decreases in mean creatinine clearance observed early in the whole population, in only six patients (7.8%) was therapy discontinued due to renal failure, which always recovered after treatment discontinuation. In eight patients (10.4%) therapy was stopped due to infusion-related side effects. Seven patients died while under antifungal therapy without relevant signs of AmB-d-associated toxicity. CONCLUSIONS: Our prospective experience confirms that adequate hydration (about 1500 ml/m2 of body surface) and careful electrolyte supplementation are simple measures able to contain nephrotoxicity and to permit adequate antifungal therapy at least in the empirical setting.

Plasticity of mouse renal collecting duct in response to potassium depletion.

Plasticity of mouse renal collecting duct in response to potassium depletion.--Renal collecting ducts are the main sites for regulation of whole body potassium balance. Changes in dietary intake of potassium induce pleiotropic adaptations of collecting duct cells, which include alterations of ion and water transport properties along with an hypertrophic response. To study the pleiotropic adaptation of the outer medullary collecting duct (OMCD) to dietary potassium depletion, we combined functional studies of renal function (ion, water, and acid/base handling), analysis of OMCD hypertrophy (electron microscopy) and hyperplasia (PCNA labeling), and large scale analysis of gene expression (transcriptome analysis). The transcriptome of OMCD was compared in mice fed either a normal or a potassium-depleted diet for 3 days using serial analysis of gene expression (SAGE) adapted for downsized extracts. SAGE is based on the generation of transcript-specific tag libraries. Approximately 20,000 tags corresponding to 10,000 different molecular species were sequenced in each library. Among the 186 tags differentially expressed (P < 0.05) between the two libraries, 120 were overexpressed and 66 were downregulated. The SAGE expression profile obtained in the control library was representative of different functional classes of proteins and of the two cell types (principal and alpha-intercalated cells) constituting the OMCD. Combined with gene expression analysis, results of functional and morphological studies allowed us to identify candidate genes for distinct physiological processes modified by potassium depletion: sodium, potassium, and water handling, hyperplasia and hypertrophy. Finally, comparison of mouse and human OMCD transcriptomes allowed us to address the question of the relevance of the mouse as a model for human physiology and pathophysiology.

Effects of potassium deficiency on potassium, polyamines and amino acids in mouse tissues.

Sexual dimorphism in potassium content was found in plasma, kidney, heart and skeletal muscle of CD1 mice. We observed that feeding mice with a K(+)-deficient diet had an uneven and gender-dependent effect on organ weight and tissue potassium concentrations. Treatment produced a marked decrease in plasma, pancreas and skeletal muscle K(+) levels in both sexes, and a reduction in kidney, liver and heart potassium concentrations in females. Moreover, K(+) deficiency produced a 2-3-fold increase in the concentrations of cationic amino acids, such as arginine and lysine in both heart and skeletal muscle of the two sexes, a slight increase ( approximately 37%) in renal arginine in the male mice. The concentrations of these amino acids in plasma and other tissues in both sexes remained unaltered. Polyamine levels in heart, liver, skeletal muscle and pancreas from male and female mice were not affected by K(+) deficiency. However, in the male kidney potassium deficiency was accompanied by an increase of putrescine and spermidine concentration, and a reduction of putrescine excretion into the urine, even though renal K(+) concentration was not significantly affected and ornithine decarboxylase activity was dramatically decreased. The general lack of correlation between tissue potassium decrease and the increase in organic cations suggests that it is unlikely that the changes observed could be related with an attempt of the tissues to compensate for the reduction in cellular positive charge produced by the fall in K(+) content. The mechanisms by which these changes are produced are discussed, but their physiological implications remain to be determined.

[Therapy of cardiac arrhythmias. Clinical significance of potassium- and magnesium aspartate in arrhythmias]. / Therapie von Herzrhythmusstörungen. Die klinische Bedeutung von Kalium- und Magnesiumaspartat bei Arrhythmien.

UNLABELLED: Potassium and magnesium deficiencies usually coexist and represent a risk factor for cardiac arrhythmias. Serum levels--in particular of magnesium--are inconclusive for establishing a possible electrolyte deficiency. Basic treatment of arrhythmia should therefore include the administration of potassium and magnesium, since the benefit is great, and the possible side effects is negligible. A placebo-controlled study involving patients with cardiac arrhythmias revealed that appreciably fewer ventricular asystoles occurred after three weeks of treatment with potassium and magnesium aspartate, even when serum levels were within the normal range prior to initiating treatment. Patients older than 50, and those with previous coronary heart disease and/or myocardial infarction derived particular benefit from this form of treatment. CONCLUSION: These results underscore the key role played by potassium and magnesium in the treatment of cardiac arrhythmias.

Variaçöes dos níveis séricos de sódio, potássio e glicose de cäes em choque séptico / Sodium, potassium and glucose serum levels changes in dogs with endotoxic shock

Foram avaliados os níveis séricos de sódio, potássio e glicose em trinta e cinco cäes, machos e fêmeas, que se apresentaram em estado de choque séptico decorrente da gastrenterite hemorrágica, antes e após terapia sintomática (Ringer com lactato de sódio e glicose), com a finalidade de se derterminar a melhora clínica obtida. Observou-se que 74,2 por cento dos animais apresentavam hipocalemia, 57,1 por cento hipoglicemia e 60 por cento discreta hiponatremia, quando da primeira colheita. Após 2 horas da instituiçäo da terapia sintomática, observou-se que a hipopotassemia ainda persistia, porém a hipoglicemia fora suficientemente corrigida (apenas 5,8 por cento mantiveram-se hipoglicêmicos). Conclui-se que a terapia sintomática é efetiva para a correçäo dos valores glicêmicos, porém näo é capaz de repor a deficiência de potássio apresentada por estes animais, devendo ser entäo acrescida deste íon.