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Oral sodium bicarbonate in people on haemodialysis: a randomised controlled trial.
Kourtellidou, SI, Ashby, DR, Johansson, LR
BMC nephrology. 2021;(1):346
Abstract
BACKGROUND Adverse events and mortality tend to cluster around dialysis sessions, potentially due to the impact of the saw-toothed profile of uraemic toxins such as potassium, peaking pre-dialysis and rapidly dropping during dialysis. Acidosis could be contributing to this harm by exacerbating a rise in potassium. The objectives of this study were to investigate the effects of oral bicarbonate treatment on reducing inter-dialytic potassium gain as well as other clinical consequences of preserving muscle mass and function and reducing intradialytic arrhythmia risk in people on haemodialysis. METHODS Open-label randomised controlled trial in a single-centre (London, UK). Forty-three clinically stable adults on haemodialysis were recruited, with a 6 month average pre-dialysis serum bicarbonate level < 22 mmol/l and potassium > 4 mmol/l. Thirty-three participants completed the study. Oral sodium bicarbonate tablets titrated up to a maximum of 3 g bd (6 g total) in intervention group for 12 weeks versus no treatment in the control group. Outcomes compared intervention versus non-intervention phases in the treated group and equivalent time points in the control group: pre- and post-dialysis serum potassium; nutritional assessments: muscle mass and handgrip strength and electrocardiograms (ECGs) pre and post dialysis. RESULTS Participants took an average of 3.7 ± 0.5 g sodium bicarbonate a day. In the intervention group, inter-dialytic potassium gain was reduced from 1.90 ± 0.60 to 1.69 ± 0.49 mmol/l (p = 0.032) and pre-dialysis potassium was reduced from 4.96 ± 0.62 to 4.79 ± 0.49 mmol/l without dietary change. Pre-dialysis bicarbonate increased from 18.15 ± 1.35 to 20.27 ± 1.88 mmol/l, however with an increase in blood pressure. Nutritionally, lean tissue mass was reduced in the controls suggesting less catabolism in the intervention group. There was no change in ECGs. Limitations are small sample size and unblinded study design lacking a placebo, with several participants failing to achieve the target of 22 mmol/l serum bicarbonate levels due mainly to tablet burden. CONCLUSION Oral sodium bicarbonate reduced bicarbonate loss and potassium gain in the inter-dialytic period, and may also preserve lean tissue mass. TRIAL REGISTRATION The study was registered prospectively on 06/08/2015 with EU Clinical Trials Register EudraCT number 2015-001439-20 .
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Effect of Increased Potassium Intake on Adrenal Cortical and Cardiovascular Responses to Angiotensin II: A Randomized Crossover Study.
Dreier, R, Andersen, UB, Forman, JL, Sheykhzade, M, Egfjord, M, Jeppesen, JL
Journal of the American Heart Association. 2021;(9):e018716
Abstract
Background Increased potassium intake lowers blood pressure in patients with hypertension, but increased potassium intake also elevates plasma concentrations of the blood pressure-raising hormone aldosterone. Besides its well-described renal effects, aldosterone is also believed to have vascular effects, acting through mineralocorticoid receptors present in endothelial and vascular smooth muscle cells, although mineralocorticoid receptors-independent actions are also thought to be involved. Methods and Results To gain further insight into the effect of increased potassium intake and potassium-stimulated hyperaldosteronism on the human cardiovascular system, we conducted a randomized placebo-controlled double-blind crossover study in 25 healthy normotensive men, where 4 weeks treatment with a potassium supplement (90 mmol/day) was compared with 4 weeks on placebo. At the end of each treatment period, we measured potassium and aldosterone in plasma and performed an angiotensin II (AngII) infusion experiment, during which we assessed the aldosterone response in plasma. Hemodynamics were also monitored during the AngII infusion using ECG, impedance cardiography, finger plethysmography (blood pressure-monitoring), and Doppler ultrasound. The study showed that higher potassium intake increased plasma potassium (mean±SD, 4.3±0.2 versus 4.0±0.2 mmol/L; P=0.0002) and aldosterone (median [interquartile range], 440 [336-521] versus 237 [173-386] pmol/L; P<0.0001), and based on a linear mixed model for repeated measurements, increased potassium intake potentiated AngII-stimulated aldosterone secretion (P=0.0020). In contrast, the hemodynamic responses (blood pressure, total peripheral resistance, cardiac output, and renal artery blood flow) to AngII were similar after potassium and placebo. Conclusions Increased potassium intake potentiates AngII-stimulated aldosterone secretion without affecting systemic cardiovascular hemodynamics in healthy normotensive men. Registration EudraCT Number: 2013-004460-66; URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02380157.
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Randomized Trial on the Effects of Dietary Potassium on Blood Pressure and Serum Potassium Levels in Adults with Chronic Kidney Disease.
Turban, S, Juraschek, SP, Miller, ER, Anderson, CAM, White, K, Charleston, J, Appel, LJ
Nutrients. 2021;(8)
Abstract
In the general population, an increased potassium (K) intake lowers blood pressure (BP). The effects of K have not been well-studied in individuals with chronic kidney disease (CKD). This randomized feeding trial with a 2-period crossover design compared the effects of diets containing 100 and 40 mmol K/day on BP in 29 adults with stage 3 CKD and treated or untreated systolic BP (SBP) 120-159 mmHg and diastolic BP (DBP) <100 mmHg. The primary outcome was 24 h ambulatory systolic BP. The higher-versus lower-K diet had no significant effect on 24 h SBP (-2.12 mm Hg; p = 0.16) and DBP (-0.70 mm Hg; p = 0.44). Corresponding differences in clinic BP were -4.21 mm Hg for SBP (p = 0.054) and -0.08 mm Hg for DBP (p = 0.94). On the higher-K diet, mean serum K increased by 0.21 mmol/L (p = 0.003) compared to the lower-K diet; two participants had confirmed hyperkalemia (serum K ≥ 5.5 mmol/L). In conclusion, a higher dietary intake of K did not lower 24 h SBP, while clinic SBP reduction was of borderline statistical significance. Additional trials are warranted to understand the health effects of increased K intake in individuals with CKD.
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A single oral glucose load decreases arterial plasma [K+ ] during exercise and recovery.
Steward, CH, Smith, R, Stepto, NK, Brown, M, Ng, I, McKenna, MJ
Physiological reports. 2021;(11):e14889
Abstract
AIM: We investigated whether acute carbohydrate ingestion reduced arterial potassium concentration ([K+ ]) during and after intense exercise and delayed fatigue. METHODS In a randomized, double-blind crossover design, eight males ingested 300 ml water containing 75 g glucose (CHO) or placebo (CON); rested for 60 min, then performed high-intensity intermittent cycling (HIIC) at 130% V˙O2peak , comprising three 45-s exercise bouts (EB), then a fourth EB until fatigue. Radial arterial (a) and antecubital venous (v) blood was sampled at rest, before, during and after HIIC and analyzed for plasma ions and metabolites, with forearm arteriovenous differences (a-v diff) calculated to assess inactive forearm muscle effects. RESULTS Glucose ingestion elevated [glucose]a and [insulin]a above CON (p = .001), being, respectively, ~2- and ~5-fold higher during CHO at 60 min after ingestion (p = .001). Plasma [K+ ]a rose during and declined following each exercise bout in HIIC (p = .001), falling below baseline at 5 min post-exercise (p = .007). Both [K+ ]a and [K+ ]v were lower during CHO (p = .036, p = .001, respectively, treatment main effect). The [K+ ]a-v diff across the forearm widened during exercise (p = .001), returned to baseline during recovery, and was greater in CHO than CON during EB1, EB2 (p = .001) and EB3 (p = .005). Time to fatigue did not differ between trials. CONCLUSION Acute oral glucose ingestion, as used in a glucose tolerance test, induced a small, systemic K+ -lowering effect before, during, and after HIIC, that was detectable in both arterial and venous plasma. This likely reflects insulin-mediated, increased Na+ ,K+ -ATPase induced K+ uptake into non-contracting muscles. However, glucose ingestion did not delay fatigue.
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Interim effects of salt substitution on urinary electrolytes and blood pressure in the China Salt Substitute and Stroke Study (SSaSS).
Huang, L, Tian, M, Yu, J, Li, Q, Liu, Y, Yin, X, Wu, JH, Marklund, M, Wu, Y, Li, N, et al
American heart journal. 2020;:136-145
Abstract
The Salt Substitute and Stroke Study is an ongoing 5-year large-scale cluster randomized trial investigating the effects of potassium-enriched salt substitute compared to usual salt on the risk of stroke. The study involves 600 villages and 20,996 individuals in rural China. Intermediate risk markers were measured in a random subsample of villages every 12 months over 3 years to track progress against key assumptions underlying study design. Measures of 24-hour urinary sodium, 24-hour urinary potassium, blood pressure and participants' use of salt substitute were recorded, with differences between intervention and control groups estimated using generalized linear mixed models. The primary outcome of annual event rate in the two groups combined was determined by dividing confirmed fatal and non-fatal strokes by total follow-up time in the first 2 years. The mean differences (95% CI) were -0.32 g (-0.68 to 0.05) for 24-hour urinary sodium, +0.77 g (+0.60 to +0.93) for 24-hour urinary potassium, -2.65 mmHg (-4.32 to -0.97) for systolic blood pressure and +0.30 mmHg (-0.72 to +1.32) for diastolic blood pressure. Use of salt substitute was reported by 97.5% in the intervention group versus 4.2% in the control group (P<.0001). The overall estimated annual event rate for fatal and non-fatal stroke was 3.2%. The systolic blood pressure difference and the annual stroke rate were both in line with the statistical assumptions underlying study design. The trial should be well placed to address the primary hypothesis at completion of follow-up.
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Effect of Steamed Potato Bread Intake on Glucose, Lipids, and Urinary Na+ and K+: A Randomized Controlled Trial with Adolescents.
Xu, H, Guo, Y, Lu, S, Ma, Y, Wang, X, Zhao, L, Sun, J
International journal of environmental research and public health. 2020;(6)
Abstract
Although potatoes are highly nutritious, many epidemiological studies have connected their consumption with abnormal lipids, diabetes, and hypertension. Steamed potato bread has recently become one of China's staple foods. A randomized controlled trial was designed to evaluate the effect of steamed potato bread consumption on Chinese adolescents. Four classes from a high school were randomly selected and assigned to the intervention group (two classes) or control group (two classes). The steamed wheat bread (100% raw wheat flour) and potato bread (raw wheat flour to cooked potato flour ratio of 3:7) were provided to the control group and intervention group as staple food once a school day for 8 weeks, respectively. Compared with the control group, the intervention group had significant net changes in systolic blood pressure (4.6 mmHg, p = 0.010), insulin (-4.35 mIU/L, p < 0.001), total cholesterol (-0.13 mmol/L, p = 0.032), and high-density lipoproteins cholesterol (-0.07 mmol/L, p = 0.010). The urinary level of Na+/K+ did not differ between the groups. In conclusion, the intake of steamed potato bread for 8 weeks resulted in positive effects on the total cholesterol and insulin profiles but a negative effect on the systolic blood pressure and high-density lipoproteins cholesterol of adolescents.
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Potassium infusion increases the likelihood of conversion of recent-onset atrial fibrillation-A single-blinded, randomized clinical trial.
Tazmini, K, Fraz, MSA, Nymo, SH, Stokke, MK, Louch, WE, Øie, E
American heart journal. 2020;:114-124
Abstract
BACKGROUND The optimal antiarrhythmic management of recent-onset atrial fibrillation (ROAF) or atrial flutter is controversial and there is a considerable variability in clinical treatment strategies. It is not known if potassium infusion has the potential to convert ROAF or atrial flutter to sinus rhythm (SR). Therefore, we aimed to investigate if patients with ROAF or atrial flutter and plasma-potassium levels ≤4.0 mmol/L have increased probability to convert to SR if the plasma-potassium level is increased towards the upper reference range (4.1-5.0 mmol/L). METHODS In a placebo-controlled, single-blinded trial, patients with ROAF or atrial flutter and plasma-potassium ≤4.0 mmol/L presenting between April 2013 and November 2017 were randomized to receive potassium chloride (KCl) infusion (n = 60) or placebo (n = 53). Patients in the KCl group received infusions at one of three different rates: 9.4 mmol/h (n = 11), 12 mmol/h (n = 19), or 15 mmol/h (n = 30). RESULTS There was no statistical difference in the number of conversions to SR between the KCl group and placebo [logrank test, P = .29; hazard ratio (HR) 1.20 (CI 0.72-1.98)]. However, KCl-infused patients who achieved an above-median hourly increase in plasma-potassium (>0.047 mmol/h) exhibited a significantly higher conversion rate compared with placebo [logrank P = .002; HR 2.40 (CI 1.36-4.21)] and KCl patients with below-median change in plasma-potassium [logrank P < .001; HR 4.41 (CI 2.07-9.40)]. Due to pain at the infusion site, the infusion was prematurely terminated in 10 patients (17%). CONCLUSIONS Although increasing plasma-potassium levels did not significantly augment conversion of ROAF or atrial flutter to SR in patients with potassium levels in the lower-normal range, our results indicate that this treatment may be effective when a rapid increase in potassium concentration is tolerated and achieved.
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Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase II, Randomized, Double-blind, Placebo-controlled Study (ENERGIZE).
Peacock, WF, Rafique, Z, Vishnevskiy, K, Michelson, E, Vishneva, E, Zvereva, T, Nahra, R, Li, D, Miller, J
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2020;(6):475-486
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Abstract
OBJECTIVES Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED). METHODS This exploratory, phase II, multicenter, randomized, double-blind, placebo-controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10-hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum potassium (sK+ ) from baseline until 4 hours after start of dosing. RESULTS Overall, 70 patients were randomized (SZC n = 33, placebo n = 37), of whom 50.0% were male. Their mean (± standard deviation [±SD]) age was 59.0 (±13.8) years and mean initial sK+ was similar between groups (SZC 6.4 mmol/L, placebo 6.5 mmol/L). The least squares mean (±SD) sK+ change from baseline to 4 hours was -0.41 (±0.11) mmol/L and -0.27 (±0.10) mmol/L with SZC and placebo, respectively (difference = -0.13 mmol/L, 95% confidence interval [CI] = -0.44 to 0.17). A greater reduction in mean (±SD) sK+ from baseline occurred with SZC compared with placebo at 2 hours: -0.72 (±0.12) versus -0.36 (±0.11) mmol/L (LSM difference = -0.35 mmol/L, 95% CI = -0.68 to -0.02), respectively. A numerically lower proportion of patients in the SZC group required additional potassium-lowering therapy due to hyperkalemia at 0 to 4 hours versus placebo (15.6% vs. 30.6%, respectively; odds ratio = 0.40, 95% CI = 0.09 to 1.77). Comparable proportions of patients experienced adverse events in both treatment groups at 0 to 24 hours. CONCLUSIONS This pilot study suggested that SZC with insulin and glucose may provide an incremental benefit in the emergency treatment of hyperkalemia over insulin and glucose alone.
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Effects of Potassium or Sodium Supplementation on Mineral Homeostasis: A Controlled Dietary Intervention Study.
Humalda, JK, Yeung, SMH, Geleijnse, JM, Gijsbers, L, Riphagen, IJ, Hoorn, EJ, Rotmans, JI, Vogt, L, Navis, G, Bakker, SJL, et al
The Journal of clinical endocrinology and metabolism. 2020;(9):e3246-56
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CONTEXT Although dietary potassium and sodium intake may influence calcium-phosphate metabolism and bone health, the effects on bone mineral parameters, including fibroblast growth factor 23 (FGF23), are unclear. OBJECTIVE Here, we investigated the effects of potassium or sodium supplementation on bone mineral parameters. DESIGN, SETTING, PARTICIPANTS We performed a post hoc analysis of a dietary controlled randomized, blinded, placebo-controlled crossover trial. Prehypertensive individuals not using antihypertensive medication (n = 36) received capsules containing potassium chloride (3 g/d), sodium chloride (3 g/d), or placebo. Linear mixed-effect models were used to estimate treatment effects. RESULTS Potassium supplementation increased plasma phosphate (from 1.10 ± 0.19 to 1.15 ± 0.19 mmol/L, P = 0.004), in line with an increase in tubular maximum of phosphate reabsorption (from 0.93 ± 0.21 to 1.01 ± 0.20 mmol/L, P < 0.001). FGF23 decreased (114.3 [96.8-135.0] to 108.5 [93.5-125.9] RU/mL, P = 0.01), without change in parathyroid hormone and 25-hydroxy vitamin D3. Fractional calcium excretion decreased (from 1.25 ± 0.50 to 1.11 ± 0.46 %, P = 0.03) without change in plasma calcium. Sodium supplementation decreased both plasma phosphate (from 1.10 ± 0.19 to 1.06 ± 0.21 mmol/L, P = 0.03) and FGF23 (from 114.3 [96.8-135.0] to 108.7 [92.3-128.1] RU/mL, P = 0.02). Urinary and fractional calcium excretion increased (from 4.28 ± 1.91 to 5.45 ± 2.51 mmol/24 hours, P < 0.001, and from 1.25 ± 0.50 to 1.44 ± 0.54 %, P = 0.004, respectively). CONCLUSIONS Potassium supplementation led to a decrease in FGF23, which was accompanied by increase in plasma phosphate and decreased calcium excretion. Sodium supplementation reduced FGF23, but this was accompanied by decrease in phosphate and increase in fractional calcium excretion. Our results indicate distinct effects of potassium and sodium intake on bone mineral parameters, including FGF23. CLINICAL TRIAL REGISTRATION NUMBER NCT01575041.
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Effects of Dexmedetomidine on Blood Glucose and Serum Potassium Levels in Children Undergoing General Anesthesia: A Secondary Analysis of Safety Endpoints During a Randomized Controlled Trial.
Görges, M, Poznikoff, AK, West, NC, Brodie, SM, Brant, RF, Whyte, SD
Anesthesia and analgesia. 2019;(4):1093-1099
Abstract
BACKGROUND Dexmedetomidine is a highly selective α2-adrenergic agonist, which is increasingly used in pediatric anesthesia and intensive care. Potential adverse effects that have not been rigorously evaluated in children include its effects on blood glucose and serum potassium concentrations, which are relevant due to the associations of derangements of both parameters with undesired outcomes. We investigated the effects of 3 different doses of dexmedetomidine on these outcomes in a randomized controlled trial in children undergoing elective surgery. METHODS Sixty-four American Society of Anesthesiologists I-II children were randomized to receive either dexmedetomidine 0.25 µg/kg, dexmedetomidine 0.5 µg/kg, dexmedetomidine 0.75 µg/kg, or 0 µg/kg (control), as a bolus administered over 60 seconds after induction of anesthesia. Changes in plasma glucose and serum potassium concentrations were measured in venous blood sampled before and at 15 and 30 minutes after study drug administration. Data were plotted within and between groups and analyzed using a constrained longitudinal data approach. RESULTS Forty-nine children completed the study. Mean glucose levels at 15 and 30 minutes were elevated with estimated changes from baseline of 0.37 mmol/L (95% CI, 0.29-0.45 mmol/L) and 0.05 mmol/L (95% CI, 0.00-0.10 mmol/L), respectively. At 15 minutes, there was a linear dose-response relationship (1.07 mmol/L/μg/kg [95% CI, 0.57-1.58 mmol/L/μg/kg]), but there was no appreciable effect of dexmedetomidine at 30 minutes (0.15 mmol/L/μg/kg [95% CI, -0.40 to 0.70 mmol/L/μg/kg]). Potassium levels were depressed relative to baseline, with a mean difference at 15 minutes of -0.20 mEq/L (95% CI, -0.28 to -0.12 mEq/L) and at 30 minutes of -0.12 mEq/L (95% CI, -0.15 to -0.08 mEq/L), but there was no appreciable effect of dexmedetomidine at either time. CONCLUSIONS Small elevations in glucose and decreases in potassium were observed after induction of anesthesia in children. The elevation in glucose at 15 minutes depended on the dose of dexmedetomidine administered. These preliminary data warrant further investigation.