Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials.

Background Epidemiologic studies, including trials, suggest an association between potassium intake and blood pressure (BP). However, the strength and shape of this relationship is uncertain. Methods and Results We performed a meta-analysis to explore the dose-response relationship between potassium supplementation and BP in randomized-controlled trials with a duration ≥4 weeks using the recently developed 1-stage cubic spline regression model. This model allows use of trials with at least 2 exposure categories. We identified 32 eligible trials. Most were conducted in adults with hypertension using a crossover design and potassium supplementation doses that ranged from 30 to 140 mmol/d. We observed a U-shaped relationship between 24-hour active and control arm differences in potassium excretion and BP levels, with weakening of the BP reduction effect above differences of 30 mmol/d and a BP increase above differences ≈80 mmol/d. Achieved potassium excretion analysis also identified a U-shaped relationship. The BP-lowering effects of potassium supplementation were stronger in participants with hypertension and at higher levels of sodium intake. The BP increase with high potassium excretion was noted in participants with antihypertensive drug-treated hypertension but not in their untreated counterparts. Conclusions We identified a nonlinear relationship between potassium intake and both systolic and diastolic BP, although estimates for BP effects of high potassium intakes should be interpreted with caution because of limited availability of trials. Our findings indicate an adequate intake of potassium is desirable to achieve a lower BP level but suggest excessive potassium supplementation should be avoided, particularly in specific subgroups.

Zinc finger protein 5 (ZFP5) associates with ethylene signaling to regulate the phosphate and potassium deficiency-induced root hair development in Arabidopsis.

KEY MESSAGE: Zinc finger protein transcription factor ZFP5 positively regulates root hair elongation in response to Pi and potassium deficiency by mainly activating the expression of EIN2 in Arabidopsis. Phosphate (Pi) and potassium (K+) are major plant nutrients required for plant growth and development, and plants respond to low-nutrient conditions via metabolic and morphology changes. The C2H2 transcription factor ZFP5 is a key regulator of trichome and root hair development in Arabidopsis. However, its role in regulating root hair development under nutrient deprivations remains unknown. Here, we show that Pi and potassium deficiency could not restore the short root hair phenotype of zfp5 mutant and ZFP5 RNAi lines to wild type level. The deprivation of either of these nutrients also induced the expression of ZFP5 and the activity of an ethylene reporter, pEBS:GUS. The significant reduction of root hair length in ein2-1 and ein3-1 as compared to wild-type under Pi and potassium deficiency supports the involvement of ethylene in root hair elongation. Furthermore, the application of 1-aminocyclopropane-1-carboxylic acid (ACC) significantly enhanced the expression level of ZFP5 while the application of 2-aminoethoxyvinyl glycine (AVG) had the opposite effect when either Pi or potassium was deprived. Further experiments reveal that ZFP5 mainly regulates transcription of ETHYLENE INSENSITIVE 2 (EIN2) to control deficiency-mediated root hair development through ethylene signaling. Generally, these results suggest that ZFP5 regulates root hair elongation by interacting with ethylene signaling mainly through regulates the expression of EIN2 in response to Pi and potassium deficiency in Arabidopsis.

Nonadherence to potassium replacement protocol leads to prolonged management of diabetic ketoacidosis.

Introduction Diabetic ketoacidosis is a life-threatening condition that requires prompt management. Objectives We aimed to assess the impact of adherence to potassium replacement protocol according to the guidelines of Diabetes Poland on the duration of diabetic ketoacidosis (DKA) treatment. Patients and methods This retrospective analysis included 242 adults (median age, 27 years; range, 21-38 years). Nonadherence to potassium replacement protocol was assessed, along with the relationship between nonadherence and duration of DKA management. Nonadherence to the protocol was defined as too low or too high doses of potassium compared with the recommended potassium replacement protocol. Results The median duration of DKA treatment was longer in the nonadherent group than in the adherent group: 37 hours (interquartile range [IQR], 27-48) and 30 hours (IQR, 17-43), respectively (P = 0.005). Treatment duration correlated positively with nonadherence to potassium replacement protocol (r = 0.18; P = 0.005) and severity of DKA (r = 0.52; P <0.0001). Stepwise multivariate linear regression analysis indicated nonadherence to the protocol (ß = 0.14; P = 0.02) and severity of DKA (ß = 0.43; P <0.0001) as predictors of treatment duration, after adjustment for body mass index and age (R2 = 0.28; P <0.0001). Conclusions Nonadherence to potassium replacement protocol leads to prolongation of DKA management. Medical staff should be educated about the benefits of potassium replacement and precision in potassium administration and dosing in patients with DKA.

A case report of Gitelman syndrome resulting from two novel mutations in SLC12A3 gene / El caso del síndrome de Gitelman causado por dos nuevas mutaciones en el gen SLC12A3

Introduction: Hypokalaemia is a common clinical problem. A potential but commonly overlooked cause of hypokalaemia is Gitelman syndrome. Material and methods: A 26-year-old man was admitted to the hospital due to syncope with general and muscular weakness and muscle cramps. The patient's history revealed previous recurrent syncope events associated to hypokalaemia with the lowest serum potassium value being 2.6mmol/l. At admission, blood pressure was normal and no changes were found at physical examination. Laboratory tests showed mild hypokalaemia (3.0mmol/l), hypomagnesaemia (1.36mg/dl), hypocalciuria (< 40mg/24h), and metabolic alkalosis (HCO3− 29.7mmol/l, BE 5.3mmol/l). Results: Further laboratory tests (FeK, TTKG) confirmed inappropriate kaliuresis. Conn's disease was excluded by hormonal and imaging assessments. Genetic testing was performed and two novel heterozygous mutations: c.35_36insA and c.1095+5G>A were found in transcriptNM_000339.2 in SLC12A3 gene. Conclusion: The patient was diagnosed with Gitelman syndrome and was treated with supplements of potassium and magnesium (AU)

Introducción: La hipopotasemia es un problema clínico común. El síndrome de Gitelman es una posible causa de hipopotasemia a veces no reconocida. Material y métodos: Un hombre de 26 años de edad ingresa en un hospital por causa de un síncope, debilidad generalizada y calambres musculares. La historia clínica del paciente reveló la incidencia del síncope con hipopotasemia recurrente con el valor más bajo de potasio en 2,6mmol/l. En el ingreso, el paciente presentaba una presión arterial normal y la exploración física no reveló ninguna enfermedad. La evaluación del laboratorio demostró una hipopotasemia leve (K+ 3,0mmol/l), hipomagnesemia (Mg 1,36mg/dl), hipocalciuria (<40mg/24h) y alcalosis metabólica (HCO3- 29,7mmol/l, exceso de base 5,3mmol/l). Resultados: Otras pruebas de laboratorio (FeK, TTKG) confirman una caliuresis inadecuada. La enfermedad de Conn fue excluida tras la evaluación hormonal y radiológica. Se realizaron las pruebas genéticas y 2 mutaciones heterocigóticas: c.35_36insA y c.1095+5G>A fueron encontradas en la transcripción NM_000339.2 del gen SLC12A3. Conclusión: El paciente fue diagnosticado con el síndrome de Gitelman y fue tratado con suplementos de potasio y magnesio (AU)

Treatment of hypokalemic periodic paralysis with topiramate.

Hypokalemic periodic paralysis (hypoPP), the most common form of periodic paralysis, is a disorder characterized by attacks of transient muscle weakness associated with a drop in serum potassium level.The mainstay of treatment is potassium supplementation and drugs that inhibit the enzyme carbonic anhydrase. In this report we describe 11-year-old twins with hypoPP who were treated with topiramate, an anti-epileptic drug known to have carbonic anhydrase inhibitory properties. The patients experienced a decrease in the severity of their attacks upon initiation of treatment. Topiramate may warrant further investigation as a treatment option in hypoPP.

[Potassium magnesium homeostasis: physiology, pathophysiology, clinical consequences of deficiency and pharmacological correction].

The metabolism of K and Mg is closely linked. Mg deficiency may arise together with and contribute to the persistence of K deficiency. Isolated disturbances of K balance do not produce secondary abnormalities in Mg homeostasis. In contrast, primary disturbances in Mg balance, particularly Mg depletion, produce secondary K depletion. This appears to result from an inability of the cell to maintain the normally high intracellular concentration of K, perhaps as a result of an increase in membrane permeability to K and / or inhibition of Na+-K+-ATPase. Cases of Mg deficiency accompanying with Mg-dependent or -independent K deficiency are not uncommon among the general population. K and Mg deficiencies are found in patients with chronic alcoholism, cardiac diseases, diabetes mellitus (type II), genetic forms of renal potassium and magnesium wasting (Gitelman's and Bartter's syndromes), severe diarrhea and vomiting, malnutrition, during therapy with some kind of drugs. Various K-Mg salts allowing simultaneously eliminating deficiency of Mg and K are described in the literature. K-Mg aspartate is most distributed among K-Mg salts. It can be used as adjuvant therapy in ischaemic heart disease (in angina pectoris and conditions after myocardial infarction), prophylaxis and adjuvant therapy of cardiac arrhythmia (e.g. prevention of toxic symptoms during therapy with digoxin). Differences in metabolism and utilisation of D- and L-amino acids probably may effect on pharmacological properties of K-Mg L- and D-aspartates, and what is more pharmacological doses of Mg and K salts may induce toxicity which differs according to the nature of the anions. In our research it was established, that L-aspartate salts are better delivery forms for cations such as Mg and K than D-aspartate salts. K-Mg L-aspartate can be more beneficial in the treatment of several forms of primary Mg and K deficiency than K-Mg DL-aspartate and K-Mg D-aspartate.

Cesium chloride protects cerebellar granule neurons from apoptosis induced by low potassium.

Neuronal apoptosis plays a critical role in the pathogenesis of neurodegenerative disorders, and neuroprotective agents targeting apoptotic signaling could have therapeutic use. Here we report that cesium chloride, an alternative medicine in treating radiological poison and cancer, has neuroprotective actions. Serum and potassium deprivation induced cerebellar granule neurons to undergo apoptosis, which correlated with the activation of caspase-3. Cesium prevented both the activation of caspase-3 and neuronal apoptosis in a dose-dependent manner. Cesium at 8 mM increased the survival of neurons from 45 +/- 3% to 91 +/- 5% of control. Cesium's neuroprotection was not mediated by PI3/Akt or MAPK signaling pathways, since it was unable to activate either Akt or MAPK by phosphorylation. In addition, specific inhibitors of PI3 kinase and MAP kinase did not block cesium's neuroprotective effects. On the other hand, cesium inactivated GSK3beta by phosphorylation of serine-9 and GSK3beta-specific inhibitor SB415286 prevented neuronal apoptosis. These data indicate that cesium's neuroprotection is likely via inactivating GSK3beta. Furthermore, cesium also prevented H(2)O(2)-induced neuronal death (increased the survival of neurons from 72 +/- 4% to 89 +/- 3% of control). Given its relative safety and good penetration of the brain blood barrier, our findings support the potential therapeutic use of cesium in neurodegenerative diseases.

Potassium and magnesium depletions in congestive heart failure--pathophysiology, consequences and replenishment.

Congestive heart failure (CHF) is becoming more frequent worldwide. Both potassium (K) and magnesium (Mg) deficiencies are common and can be associated with risk factors and complications of heart failure (HF). The major causes of K and Mg depletions are the effects of compensatory neuroendocrine mechanisms (activation of the renin-angiotensin-aldosterone and sympathoadrenergic systems), digoxin therapy, and administration of thiazide or loop diuretic therapy in CHF. Particular attention should be paid to K and Mg restoration in CHF, because of the consequences of both deficiencies (increased arrhythmic risk, vasoconstriction), and the co-supplementation of both ions is necessary in order to achieve K repletion. Mg and K should be employed as first-line therapy in digitalis intoxication and drug-related arrhythmias, and should be considered an important adjuvant therapy in diuretic treated patients with CHF. Another possibility to restore normal K and Mg status is usage of a K, Mg sparing diuretics.

A primary Sjögren's syndrome patient with distal renal tubular acidosis, who presented with symptoms of hypokalemic periodic paralysis: Report of a case study and review of the literature.

Although renal tubular acidosis (RTA), secondary to autoimmune interstitial nephritis, develops in a large proportion of patients with Sjögren's syndrome (SS), most of the subjects are asymptomatic. Here, we shall present a 39-year-old female patient who came to us with hypokalemic periodic paralysis (HPP), and who was later diagnosed with distal RTA. The patient, who had xerostomia and xerophthalmia for a long period of time, was diagnosed with primary SS from serologic and histologic findings. The patient recovered by being prescribed potassium replacement therapy. Although renal biopsy was not performed, corticosteroids were administered because HPP indicated severe interstitial nephritis. HPP did not reoccur during a 2-year follow-up period. We also review cases with SS-related distal RTA and HPP.

In vivo 31P-MRS assessment of muscle-pH, cytolsolic-[Mg2+] and phosphorylation potential after supplementing hypokaliuric renal stone patients with potassium and magnesium salts.

Renal stone patients in rural northeast Thailand have a low potassium and magnesium status and low urinary excretion of citrate. We measured the changes of urinary citrate excretion and assessed in vivo skeletal muscle metabolism for intracellular-pH, cytosolic-[Mg(2+)] and phosphorylation potential (using the phosphorus magnetic resonance spectroscopy (31)P-MRS) after oral supplementation to hypokaliuric renal stone patients with oral potassium and magnesium salts. The patients comprised four groups: Group 1 (n = 10) control, Group 2 (n = 3), Group 3 (n = 5) and Group 4 (n = 6) supplemented for a month with potassium citrate, potassium citrate plus amino acid chelated magnesium, and potassium-magnesium citrate, respectively. Though urinary citrate excretion was increased in all three supplemented groups, the increases in intracellular-pH, cytosolic-[Mg(2+)] and phosphocreatine (PCr)/beta-ATP were prominent only in Group 3. The increase in PCr/beta-ATP was also observed in Group 4.

Thyrotoxic periodic paralysis: an unusual presentation of weakness.

Thyrotoxic periodic paralysis is a rare endocrine disorder seen predominantly in men of Asian origin. The case is reported of a patient who presented to the accident and emergency department with sudden onset of weakness of his lower limbs. Hypokalaemia was identified and treated with resolution of symptoms. Additional tests identified the patient as being thyrotoxic. He was treated with oral antithyroid drugs. It is important to consider the diagnosis of thyrotoxic periodic paralysis in patients presenting with acute onset of weakness. The report discusses the epidemiology, presentation, treatment, and complications of this condition.

[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.

The effects of potassium depletion and supplementation on blood pressure: a clinical review.

Nonpharmacologic treatment currently is recognized as an important part in the treatment of hypertension, and the role of dietary potassium intake in blood pressure (BP) control is becoming quite evident. Clinical studies have examined the mechanism by which hypokalemia can increase BP and the benefit of a large potassium intake on BP control. Epidemiologic data suggest that potassium intake and BP are correlated inversely. In normotensive subjects, those who are salt sensitive or who have a family history of hypertension appear to benefit most from the hypotensive effects of potassium supplementation. The greatest hypotensive effect of potassium supplementation occurs in patients with severe hypertension. This effect is pronounced with prolonged potassium supplementation. The antihypertensive effect of increased potassium intake appears to be mediated by several factors, which include enhancing natriuresis, modulating baroreflex sensitivity, direct vasodilation, or lowering cardiovascular reactivity to norepinephrine or angiotensin II. Potassium repletion in patients with diuretic-induced hypokalemia improves BP control. An increase in potassium intake should be included in the nonpharmacologic management of patients with uncomplicated hypertension.

[Heart rate disorders in potassium and magnesium deficiency]. / Hjerterytmeforstyrrelser ved kalium- og magnesiummangel.

Potassium and magnesium deficiencies are common in patients with heart disease. These are often coexistent and pathophysiologically related. Potassium deficiency cannot be treated without correction of concomitant magnesium deficiency. Correlations between serum levels and body stores are very poor for both ions. Therefore diagnosis and treatment of these conditions based on serum levels alone are erroneous. There is some evidence that it is primarily the intracellular depletion of these ions which is arrhythmogenic. Magnesium infusion has been proved effective in treatment of torsade de pointes ventricular tachycardia and arrhythmias induced by digoxin-intoxication, and is recommended in these conditions. Whether it is effective in other forms of arrhythmia is not yet elucidated.

Recovery of heart tissue following focal injury induced by dietary restriction of potassium.

Sixty-four Sprague-Dawley rats (initially weighing 200-225 grams) were divided into three groups. Group 1, the experimental group, was fed a potassium depleted diet for 42 days, followed by a potassium repleted diet for up to an additional 14 days. Group 2, the dietary control group, received a potassium deficient diet, but was continuously supplemented by drinking water containing potassium chloride 150 meq/L. Group 3, the control group remained on normal rat chow and tap water during the entire investigation. Quantitative morphometric analysis was used to assess the percent of myocardium occupied by lesion. These data were analyzed by an analysis of variance (ANOVA) for repeated measures, comparing the three groups with one another; a second analysis compared the myocardial lesions of the dietary experimental group during the potassium depletion and repletion periods. At the end of the dietary depletion period (day 42) focal areas of cardiac myocyte necrosis and mononuclear infiltrate were found in the experimental group. Morphometric assessment on day 42 revealed a volume fraction (Vv) of 8.61 (+/- 4.41)%, which was significantly greater (p = 0.0018), as compared with both control groups. Lesion area significantly regressed in two and one half days after potassium was supplemented in the dietary experimental group to 0.58 (+/- 0.34)% Vv (p = 0.0005). Six days after potassium was replaced in the diet, there was no significant difference between the experimental and control groups, and only a limited connective tissue scar was noted in the experimental group. The mechanism of the rapid regression of lesions and the production of only limited connective tissue scar is suggested but requires further elucidation.