Reduction In Potassium Research Articles

Abstract #1400643: Rates of Hypoglycemia with Reduced- vs. Standard-Dose Insulin for Hyperkalemia Treatment in Renal Insufficiency

The primary objective was to assess the difference in rates of hypoglycemia (blood glucose (BG) ≤70 mG/dL) when using reduced-dose (5 units) vs. standard-dose (10 units) of IV regular insulin for hyperkalemia treatment in renal insufficiency. Secondary objectives include the efficacy of insulin dose on potassium reduction and evaluating the difference in rates of severe hypoglycemia (BG ≤54 mG/dL) between the groups. This was a retrospective chart review of patients with renal insufficiency treated with IV regular insulin for hyperkalemia at a tertiary care teaching hospital from June 2020 to June 2021, with institutional review board approval. Inclusion criteria encompassed patients aged 18 years and older with elevated baseline potassium (≥5.5 mEq/L), estimated glomerular filtration rate < 30 mL/min/1.73m2, end stage renal disease, or presence of acute kidney injury, having received either 5 or 10 units of IV regular insulin for hyperkalemia, and had documented glucose and potassium levels after insulin administration. Patients who were pregnant, had diabetic ketoacidosis, or a baseline BG ≤70 mG/dL were excluded. Data collection included patient demographics, diabetes history, relevant labs at time of elevated potassium, doses of insulin and dextrose administered for hyperkalemia treatment, presence of coronavirus-19 infection, glucose levels within 6 hours and first potassium level within 24 hours following insulin administration, concurrent use of potassium-lowering agents, insulin outside of hyperkalemia treatment, or steroids, and mortality. Out of 409 patients included, 92 were in the 10-unit group and 317 in the 5-unit group. The rate of hypoglycemia in the 5-unit arm vs. the 10-unit arm was 6.9% vs. 8.7% (p=0.649), respectively. The rate of severe hypoglycemia between the 5-unit arm and the 10-unit arm was 3.2% vs 5.4% (p=0.682), respectively. The percent normalization of potassium was not statistically different between the 5-unit group and the 10-unit group (59% vs. 68%; p=0.115), with the same mean reduction in potassium from baseline (0.8 mEq/L (p=0.947)). Administration of concurrent treatments for hyperkalemia was similar between the groups, with dialysis being the only one with statistical significance in normalization of potassium. Patient characteristics that could have an impact on risk of hypoglycemia were studied and analyzed, including pre-treatment BG, history of diabetes mellitus, insulin naïve, and patient weight. In patients with hypoglycemia (n=30) vs. those without hypoglycemia (n=379), there was a significantly different mean pre-treatment BG (113 mG/dL vs. 178 mG/dL, p<0.001). There was no significant difference in rates of hypoglycemia and severe hypoglycemia between the 5-unit vs. 10-unit groups. There was no significant change in potassium normalization between the two insulin doses. Because of the small number of hypoglycemia events, larger studies are needed to better understand if 5 units of regular insulin is a safer option for the treatment of hyperkalemia in renal insufficiency.

Thiazide diuretics alone or combined with potassium-sparing diuretics to treat hypertension: a systematic review and network meta-analysis of randomized controlled trials.

The magnitude of blood pressure (BP)-lowering effects and decrease of the adverse effects of thiazide diuretics provided by potassium-sparing diuretics remain uncertain. The aim of this study was to compare the BP-lowering efficacy and the incidence of adverse effects of high (T+) and low-dose (T-) thiazide diuretics, alone or combined with high (PS+) or low-dose (PS-) potassium-sparing diuretics in patients with primary hypertension. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scopus and LILACS. Randomized double-blind placebo or active-controlled trials (RCT) with 3 weeks to 1 year of follow-up were included. Sample size, mean and standard deviation from baseline, follow-up and change from baseline values were extracted by two independent reviewers. Pairwise random effect models and Bayesian network meta-analysis models were used to compare the effects of treatments. The risk of bias in individual studies was assessed using the Rob 1.0 tool. The primary outcome was the mean difference in office SBP. Secondary outcomes were the mean difference in biochemical parameters and the incidence of nonmelanoma skin cancer. Two hundred and seventy-six double-blind RCTs involving 58 807 participants (mean age: 55 years; 45% women) were included. All treatment groups were more effective than placebo in lowering BP, with mean differences (MDs) of change from baseline ranging from -7.66 mmHg [95% credible interval (95% CrI), -8.53 to -6.79] for T- to -12.77 mmHg (95% CrI, -15.22 to -10.31) for T+PS-. T+ alone or combined with potassium-sparing was more effective in reducing BP than T-. The surface under the cumulative ranking curve (SUCRA) estimated ranking showed that the best effectiveness in lowering SBP was found for T+PS- (0.69), T+PS+ (0.65) and T+ (0.54). Compared with placebo, all treatments (except T-PS-) were associated with more potassium reduction and T+ compared with all other treatments and T- when compared with T-PS-. Compared with placebo, all active treatments (except T+PS+) showed higher elevations of uric acid. The increase of plasma glucose promoted by thiazides alone was reduced by potassium-sparing agents. Thiazides with potassium-sparing diuretics are associated with increased BP-lowering efficacy compared with thiazides alone while minimizing hypokalaemia and hyperglycaemia. These findings demonstrate that thiazide and potassium-sparing diuretic combination is preferable to thiazide alone in treating hypertension.

Kappaphycus alvarezii flours as an ingredient for seaweed‐enriched, rice‐based, snacks: raw algae pretreatment and physical properties of the dough and snacks

SummaryIn this work, the addition of pretreated Kappaphycus alvarezii flour to a rice‐based snack formulation was proposed as an alternative to producing algae‐enriched snacks adding value to this seaweed and improving the quality of the snacks. Dried algae were submitted to multiple washing cycles to allow the reduction of the natural salt concentration of the algae. After, algae were dried and milled to obtain flour. The flour was added in different concentrations (0%, 2%, 5%, and 10%) in the model formulation of rice‐based dough. Rice‐K. alvarezii snacks were produced by baking at 220 °C. The proximate composition of the raw and pretreated algae was determined, as well as the colour, texture, and microstructure of dough and snacks. The pretreatment efficiently allowed for a reduction of 78% of the initial content of sodium and an 85% reduction of potassium. The concentration of 5% and 10% of algae addition presented higher values of hardness and consistency of the dough and lower adhesiveness. At higher concentrations, the seaweed flour acts as a processing aid during the preparation steps of the snacks but does not influence the hardness of the final snacks. The pretreated K. alvarezii flour is an alternative for increasing the quality of rice‐based snacks while preserving the algae's potential health benefits.

Pharmacokinetic and Pharmacodynamic Comparison of Fluticasone Propionate/Formoterol Fumarate Administered via a Pressurized Metered-Dose Inhaler and a Novel Breath-Actuated Inhaler in Healthy Volunteers.

Introduction: Fluticasone propionate/formoterol fumarate (fluticasone/formoterol) exposures, following administration of Flutiform® K-haler®, a breath-actuated inhaler (BAI), were compared with the Flutiform pressurized metered-dose inhaler (pMDI) with/without spacer in two healthy volunteer studies. In addition, formoterol-induced systemic pharmacodynamic (PD) effects were examined in the second study. Methods: Study 1: single-dose, three-period, crossover pharmacokinetic (PK) study with oral charcoal administration. Fluticasone/formoterol 250/10 μg was administered via BAI, pMDI, or pMDI with spacer (pMDI+S). Pulmonary exposure for BAI was deemed no less than for pMDI (primary comparator) if the lower limit of 94.12% confidence intervals (CIs) for BAI:pMDI maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUCt) ratios was ≥80%. Study 2: two-stage adaptive design, both stages being single-dose, crossover without charcoal administration. The PK stage compared fluticasone/formoterol 250/10 μg via BAI, pMDI, or pMDI+S. The primary comparisons were as follows: BAI versus pMDI+S for fluticasone and BAI versus pMDI for formoterol. Systemic safety with BAI was deemed no worse than primary comparator if the upper limit of 94.12% CIs for Cmax and AUCt ratios was ≤125%. PD assessment was to be conducted if BAI safety was not confirmed in the PK stage. Based on PK results, only formoterol PD effects were evaluated. The PD stage compared fluticasone/formoterol 1500/60 μg via BAI, pMDI, or pMDI+S; fluticasone/formoterol 500/20 μg pMDI; and formoterol 60 μg pMDI. The primary endpoint was maximum reduction in serum potassium within 4 hours postdose. Equivalence was defined as 95% CIs for BAI versus pMDI+S and pMDI ratios within 0.5-2.0. Results: Study 1: lower limit of 94.12% CIs for BAI:pMDI ratios >80%. Study 2, PK stage: upper limit of 94.12% CIs for fluticasone (BAI:pMDI+S) ratios <125%; upper limit of 94.12% CIs for formoterol (BAI:pMDI) ratios >125% (for Cmax, not AUCt). Study 2, PD stage: 95% CIs for serum potassium ratios 0.7-1.3 (BAI:pMDI+S) and 0.4-1.5 (BAI:pMDI). Conclusions: Fluticasone/formoterol BAI performance was within the range observed for the pMDI with/without a spacer. Sponsor: Mundipharma Research Ltd. EudraCT 2012-003728-19 (Study 1) and 2013-000045-39 (Study 2).

Integration of Pre-Treatment with UF/RO Membrane Process for Waste Water Recovery and Reuse in Agro-Based Pulp and Paper Industry

This recent study aims to evaluate the efficacy of membrane filtration on recovery of water resource from agro-waste such as bagasse, crop-based pulp and paper mill waste. A mini pilot scale membrane system having a combination of pre-treatment filter unit (pre-filter, sediment filter and pre-carbon filter), ultra-filtration and reverse osmosis with spiral wound configuration were employed to evaluate the water reuse efficacy of effluent coming from the secondary clarifier of the conventional treatment plant of the mill. The operational conditions were optimized using Taguchi method at pH 8, temperature 32 °C, and pressure 2 bar and a flow rate of 60 l/hr. The qualities of the effluent from the secondary clarifier, and the permeate from both the combination, viz. Combination 1 (pre-treatment + ultra-filtration) and Combination 2 (pre-treatment + ultra-filtration+ reverse osmosis) were analyzed and the percentage reduction in pH, TDS, TSS, BOD, COD, Color, Lignin, Potassium and Sodium were calculated. The elimination of TDS, COD and BOD with Combination 1 was not promising (<22%). However, the installation of a RO membrane greatly reduced (>88%) the contaminants in both paper mill effluents. The obtained qualities of water from all the combinations were compared with the tolerance standard for reuse as process water. The quality of effluent from the secondary clarifier did not agree with any class of water quality. The permeate from the combination of pre-treatment and UF sufficiently reduced the TSS to reach the requirement. However, the combination of (pre-treatment + UF + RO) adequately complied with the quality standard required for reuse in the making of all grades of paper.

131 - PDE4 inhibition induces an acute and transient reduction in serum potassium in mice

131 - PDE4 inhibition induces an acute and transient reduction in serum potassium in mice

Single Dose of Sodium Zirconium Cyclosilicate Versus Sodium Polystyrene Sulfonate in Hospitalized Patients With Hyperkalemia.

Sodium zirconium cyclosilicate (SZC) is an inorganic zirconium silicate compound that selectively exchanges potassium for hydrogen and sodium. "Once" doses of SZC (with option to redose) in patients with hyperkalemia in hospitalized settings have not been evaluated. We hypothesized that a once dose of SZC would be non-inferior to sodium polystyrene sulfonate (SPS) in reducing serum potassium. The objective of our study is to evaluate the effect of a "once" dose of SZC when compared with SPS in reducing serum potassium levels. This was a retrospective analysis of patients who received either a "once" dose of SZC or single or repeated doses of SPS for hyperkalemia. The primary endpoint was mean absolute reduction in the first serum potassium value at least 4 hours after administration. The secondary efficacy endpoints were the rate of additional potassium-lowering therapies and the rate of normokalemia within 48 hours. Safety endpoints were the incidence of electrolyte abnormalities, hypoglycemia, hypertension, hypotension, and colonic necrosis. A total of 260 patients were included in the analysis. The mean initial serum potassium was similar between groups (5.6 ± 0.4). The absolute serum potassium reduction was -0.88 ± 0.64 mEq/L and -0.75 ± 0.65 mEq/L with SZC and SPS, respectively. The "once" regimen of SZC demonstrated non-inferiority compared with SPS (P < 0.0001). The proportion of patients achieving normokalemia within 48 hours and the proportion of patients receiving additional potassium-lowering therapies did not differ between groups. The "once" dose regimen (with redose option) of SZC was non-inferior to the "once" or repeated dosing regimen of SPS with regard to absolute potassium reduction. There were no significant differences in the rate of additional potassium-lowering therapies and the rate of normokalemia at 48 hours. The incidence of hypertension was less common among patients who received SZC.

Reducing dietary crude protein in broiler diets positively affects litter quality without compromising growth performance whereas a reduction in dietary electrolyte balance further improves litter quality but worsens feed efficiency

Reducing crude protein (CP) in broiler feed is a nutritional strategy that allows to partially reduce dietary soybean meal (SBM) inclusions to reduce feed costs, with proven benefits. In addition, reduction of dietary CP leads to a lower dietary electrolyte balance (dEB) due to the concomitant reduction of potassium (K). The aim of the present study is therefore two-fold: 1) to evaluate the potential of reduction of dietary CP until performance drops (1, 2 or 3 % points of reduction) and 2) to combine it with a reduction of dEB (by reducing dietary K) to validate the benefit of reduced dEB/K on litter quality without compromising performance. In total, 9100 male Ross 308 chicks were randomly allotted to 35 pens of 260 broilers. They were fed 5 dietary treatments from 10 to 20d and 20–30d.There was a “positive control” diet (CONTROL; 20.7 % CP in grower, 19.5 % CP in finisher) and 3 levels of dietary CP reduction by 1 % (CP-1 %), 2% (CP-2 %) and 3 % (CP-3 %), all diets formulated to respect at least the ideal AA profile for indispensable AA. In addition, an extra diet called “negative control” (NC CP-3 %) was formulated to have the same ingredient composition as the CP-3 % diet but with lower K and dEB level. Reducing dietary CP as low as 3 % points and maintaining AA and dEB levels resulted in similar or better production performance from 10 to 30d for weight gain, feed intake, feed conversion ratio (FCR) and carcass traits, reduced daily water intake and water-to-feed ratio, excreta N and moisture as well as lower litter moisture and footpad lesions (FPL). Reducing dEB level at − 3 % CP (negative control) increased feed intake and FCR but reduced water intake, water-to-feed ratio, and FPL. It is therefore possible to feed broilers with lower CP diets without compromising performance, with clear benefit on litter quality. As reducing dietary CP is often associated to reduced dietary K, due to lower SBM inclusion, the extent of reduction of K and the control of dEB by Na, Cl and K need to be further explored, especially on litter quality, to facilitate the adoption of low protein diets in practice.

Alterações de atributos químicos e físicos de vertissolo em área de produção de meloeiro

ABSTRACT Water quality and soil quality are of great importance for crop yield in the context of small-scale irrigated agriculture in the Northeast region of Brazil. In this respect, this study aimed to determine changes in soil fertility and resistance to root penetration caused by fertigated cropping, as compared to soil under native forest. In each area, a non-regular sampling grid was established, which consisted of 87 georeferenced points in the melon cultivated area and 8 points in the native forest area. At these points, samples were obtained at depths of 0-10, 10-20, 20-30 and 30-40 cm. The determinations performed included soil physical, chemical and mechanical attributes. Multivariate analysis techniques and geostatistical procedures were used to analyze and interpret the data. The cultivation of the Vertisol altered all the variables studied, compared to the area under native forest. Soil decompaction and increase in phosphorus content were positive effects, while organic matter decomposition and reductions in potassium, calcium, magnesium and cation exchange capacity were negative effects. Sodium content and porosity parameters were prominent factors in soil alterations.

Sodium polystyrene sulfonate versus sodium zirconium cyclosilicate for the treatment of hyperkalemia in the emergency department

BackgroundHyperkalemia accounts for over 800,000 emergency department (ED) visits in the United States each year, and has been associated with significant morbidity and mortality likely due to fatal cardiac dysrhythmias. Previous studies have demonstrated reductions in mortality when potassium levels are normalized in the ED. Cation exchange resins, such as sodium polystyrene sulfonate (SPS) and sodium zirconium cyclosilicate (SZC), may be administered as a means of definitively eliminating potassium from the body. This practice is based on physician preference and is not supported by high quality data. Two studies evaluating the use of cation exchange resins versus standard treatment in the ED demonstrated reductions in serum potassium levels within two hours of administration; however, there have been no published studies investigating these agents in a head-to-head comparison. ObjectiveThe purpose of this study was to evaluate the efficacy and safety of SPS versus SZC in lowering serum potassium in patients presenting to the ED with hyperkalemia. MethodsThis was an institutional review board-approved, retrospective cohort study conducted at a single-site ED. All patients who received medications under the “ED Hyperkalemia Treatment” order set between August 26, 2019 and May 13, 2021 were eligible for inclusion. The primary outcome was the change in serum potassium from baseline to first repeat level following SPS or SZC administration in the ED. ResultsA total of 885 patients were screened with 54 patients in the SPS group and 51 patients in the SZC group included in the final analyses. The mean change in serum potassium from baseline to first repeat level following administration of the cation exchange resin was −1.1 mEq/L for both groups. ConclusionAdministration of SPS or SZC for the treatment of hyperkalemia in the ED resulted in similar reductions in serum potassium.

Manual Single-Lumen Alternating Micro-Batch Device as Renal Replacement Therapy in Austere Environments

Introduction: Electrolyte derangements, acidosis, and volume overload remain life-threatening emergencies in people with acute kidney injury in austere environments. A single-lumen alternating micro-batch (SLAMB) dialysis technique was designed to perform renal replacement therapy using a single-lumen access, low-cost disposable bags and tubing, widely available premade fluids, and a dialysis filter. A manual variation (mSLAMB) works without electricity, battery, or a pump. We modeled mSLAMB dialysis and predicted it could achieve adequate small solute clearance, blood flow rates, and ultrafiltration accuracy. Methods: A 25- to 30-kg pediatric patient’s blood volume was simulated by a 2-L bag of expired blood and spiked with 5 g of urea initially, then with 1–2 g between experiments. Experiments had 8 cycles totaling prescription volumes of 800–2,400 mL and were conducted with different ratios of hemofiltration fluid to blood volume. Concentrations of urea and potassium, final effluent volumes, and cycle duration were measured at the end of each cycle to determine clearance, ultrafiltration accuracy, and blood flow rates. Results: Each cycle lasted 70–145 s. Experiments achieved a mean urea reduction ratio of 27.4 ± 7.1% and a mean potassium reduction of 23.4 ± 9.3%. The largest urea and potassium reduction percentage occurred with the first cycle. Increased hemofiltration fluid to blood volume ratio did not increase clearance. Mean (+/− standard deviation) blood flow ranged from 79.7 +/− 4.4 mL/min to 90.8 +/− 6.5 mL/min and increased with larger batch volume and height difference between reservoirs. Ultrafiltration accuracy ranged from 0 to 2.4% per cycle. Discussion: mSLAMB dialysis is a simple, manual, cost-effective mode of dialysis capable of providing clearance and accurate ultrafiltration. With further refinement of technique, we believe this can be a potentially lifesaving treatment in austere conditions and low-resource settings.

Investigation of leaching in steel fiber-reinforced shotcrete exposed to fresh and saline groundwater in a subsea road tunnel

The field and laboratory investigations performed in the Frøya subsea road tunnel, constructed between 1998 and 2000, focus on the degree of leaching undergone by steel fiber-reinforced shotcrete in fresh and saline groundwater. Shotcrete samples were extracted by core drilling at two locations: in the middle of the tunnel approximately 150 m below sea level, and near one of the portals. Leaching is only evident in the first location identified by portlandite reduction, potassium reduction, shotcrete density reduction, and suction porosity increase towards the traffic room. The leached depth is approximately 9 cm.

Pairwise comparison of hydrochlorothiazide and chlorthalidone responses among hypertensive patients.

This study conducted a pairwise comparison of antihypertensive and metabolic effects of hydrochlorothiazide (HCTZ) and chlorthalidone (CTD) at 25 mg/day in the same individuals to address the clinical dilemma on preferred thiazide for hypertension (HTN) management. We included 15 African American (AA) and 35 European American (EA) patients with HTN treated with HCTZ and CTD as part of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 trials, respectively. Mean reduction in systolic/diastolic blood pressure (SBP/DBP) with HCTZ versus CTD was 8/5 versus 16/8 mmHg among EA patients (p < 1.0e-5 SBP, p=0.002 DBP) and 11/8 versus 20/11 mmHg among AA patients (p=0.03 SBP, p=0.22 DBP). While CTD showed clinically meaningful benefit over HCTZ in two-thirds of participants with respect to SBP reduction and half of EA patients with respect to DBP reduction, a majority of AA patients (53%) showed similar DBP reduction with both thiazides. Sixty percent of AA patients and 29% of EA patients attained blood pressure (BP) <140/90 mmHg with both thiazides. Mean potassium (K+) reduction was greater with CTD compared to HCTZ both in EA patients (mean difference=0.35, p=0.0002) and AA patients (0.49, p=0.043). While 31% of AA patients developed severe hypokalemia on CTD, <5% of others developed severe hypokalemia. Although 46% of AA patients on CTD required K+ supplementation, only 6%-11% of others required supplementation. Overall, in the majority of EA patients, CTD was superior to HCTZ, whereas among AA patients, it was superior in a minority, and was associated with significant potassium-related risk, suggesting that guideline preferences for CTD over HCTZ are reasonable in EA patients but may be less reasonable in AA patients, particularly if the target is <140/90 mmHg.

Patiromer utilization in patients with advanced chronic kidney disease under nephrology care in Germany.

Hyperkalemia (HK) is a frequent condition in patients with chronic kidney disease (CKD) that is associated with high morbidity and mortality. Patiromer has recently been introduced as a potassium binder. Data on patiromer use in patients with CKD in the real-world setting in Europe are lacking. We describe time to discontinuation and changes in serum potassium levels among German CKD stage 3-5 patients starting patiromer. Duration of patiromer use was estimated by Kaplan-Meier curve, starting at patiromer initiation and censoring for death, dialysis, transplant or loss to follow-up. Serum potassium levels and renin-angiotensin-aldosterone system inhibitor (RAASi) use are described at baseline and during follow-up, restricted to patients remaining on patiromer. We identified 140 patiromer users within our analysis sample [81% CKD stage 4/5, 83% receiving RAASi, and median K+ 5.7 (5.4, 6.3) mmol/L]. Thirty percent of patiromer users had prior history of polystyrene sulfonate use. Overall, 95% of patiromer users stayed on treatment past 1 month, with 53% continuing for over a year. Mean serum potassium levels decreased after patiromer initiation and remained stable under treatment during follow-up (up to 180 days). Among these patients, 73%-82% used RAASis during the time periods before and after patiromer initiation, with no obvious trend indicating discontinuation. Real-world evidence of patiromer use in Germany shows that, in line with what has been observed in clinical trials, patients on patiromer have a reduction in serum potassium when used long-term. Moreover, most patients on patiromer do not discontinue treatment prior to 1 year after initiation.

Fifteen-minute consultation: Emergency management of children presenting with hyperkalaemia

Hyperkalaemia can lead to life-threatening cardiac arrhythmias. A good understanding of the physiological basis of management can help us rationalise treatment and reduce plasma potassium levels efficiently and effectively. Management...

Association between preoperative hypokalemia and postoperative complications in elderly patients: a retrospective study

BackgroundHypokalemia is a common form of electrolyte disorder, which has a higher incidence in hospitalized patients and is closely related to perioperative complications and prognosis. Due to decreased skeletal muscle mass which causes total body potassium reduction, and increased comorbidities, the elderly are more susceptible to hypokalemia.ObjectiveTo investigate preoperative hypokalemia in elderly patients and its effect on postoperative complications.MethodsData were retrospectively collected from the elderly patients who underwent elective surgery from April 2018 to March 2019 and had preoperative blood gas data available. Patients, with age 60 to 100 years, were divided into hypokalemia group (potassium level < 3.5 mmol/L) and normokalemia group (potassium level between 3.5 and 5.5 mmol/L) according to preoperative blood gas analysis. Hypokalemia can be divided into mild (potassium level 3.0 to 3.5 mmol/L), moderate (potassium level 2.5 to 3.0 mmol/L) and severe (potassium level < 2.5 mmol/L), respectively. The risk factors of preoperative hypokalemia and its impact on postoperative complications and prognosis were primary outcomes. Secondary outcomes included postanesthesia care unit (PACU) stay time and hospital length of stay (LOS).ResultsOf 987 participants, 436 (44.17%) developed preoperative hypokalemia, among them 357 (81.88%) mild, 87 (16.74%) moderate and 6 (1.38%) severe. Multivariate logistic regression showed that female gender (OR, 1.851; 95% CI, 1.415–2.421), pre-existing hypokalemia at admission (OR, 4.498; 95% CI, 2.506–8.071), and oral laxative twice or more (OR, 1.823; 95% CI, 1.266–2.624) are risk factors of preoperative hypokalemia. Gynecological and biliopancreatic surgery were more common in hypokalemia group than normokalemia group (P < 0.001, P < 0.05). There was no significant difference in postoperative complications, PACU stay time, LOS, and 30-day mortality between the two groups (all P > 0.05).ConclusionsFemale gender, pre-existing hypokalemia at admission, and oral laxative twice or more are independent risk factors for preoperative hypokalemia in elderly patients. However, postoperative complications and 30-day mortality were not increased, which may be related to monitoring blood gas analysis and prompt correction of potassium levels during surgery.

Soaking to Reduce Potassium and Phosphorus Content of Foods

To achieve and maintain normal serum potassium and phosphorus levels reducing potassium and phosphorus intake is frequently recommended for adults living with chronic kidney disease. Exploring food preparation methods to reduce potassium and phosphorus content appears warranted. The study aim is to determine the impact of soaking foods in hot water on potassium and phosphorus content in a variety of plant- and animal-based foods. Twenty foods were selected that are common staples in Brazilian diet patterns. Food was soaked for 5-10minutes in deionized water that had been brought to a boil and then removed from heat using a 5-part water to 1-part sample ratio. The potassium content was determined by flame photometry. The phosphorus content was determined by visible ultraviolet spectrophotometry. Soaking foods resulted in a reduction in potassium and phosphorus. Potassium reduction in beef, green leafy vegetables, and grains was 40-49%; in chicken, fish, and nonleafy vegetables30-39%; and tubers 10-20%. Phosphorus reduction in grains and beans was 30-39%; in nonleafy vegetables20-29%; and beef, chicken, and fish 10-20%. Soaking foods in hot water for 5-10minutes reduces potassium and phosphorus content. Using this technique to prepare foods may be a more acceptable alternative to longer demineralization periods making it easier for adults living with chronic kidney disease to follow diet recommendations.

Serum protein and electrolyte imbalances are associated with chemotherapy induced neutropenia

IntroductionCancer and its treatment using various chemotherapeutic agents can have many adverse side effects. These side effects often result in significant changes in haematological and biochemical composition of blood. As a result, the regular monitoring of serum biochemical and haematological changes plays an important role in management of disease. The present study aimed to determine the relationship between haematological and biochemical changes in neutropenic cancer patients following chemotherapy. Specifically we evaluated the association between neutrophil count and serum proteins and electrolytes. MethodsFor this purpose we analysed retrospectively collected laboratory results from two independent patient cohorts. Each cohort was divided into a control group consisting of patients with normal haematological parameters and a study group which included patients with reduced neutrophil counts. Neutropenic patients (study group) were cancer patients on chemotherapy. Results and conclusionBlood samples of cancer patients in study group showed reduction in haemoglobin, neutrophils and platelets. Neutropenic group showed a significant reduction in serum albumin, total protein, calcium, and potassium. Our results show that patients with severe neutropenia had pronounced changes in serum protein and electrolytes and increased incidence of abnormal serum protein and electrolyte level. The changes in the neutrophil counts showed a positive correlation with the changes in serum protein and electrolyte levels. A similar trend was seen in both the patient cohorts: the discovery set (176 patients) and the validation set (200 patients). Taken together our results suggest that chemotherapy-induced neutropenia is associated with dysregulation in haemoglobin, platelets, serum proteins and electrolytes.

MO151: A Randomized Controlled Trial of Sodium Zirconium Cyclosilicate Versus Standard of Care for Hyperkalaemia in Chronic Kidney Disease: Phase 4 Continuity Study Design and Rationale

Abstract BACKGROUND AND AIMS Individuals hospitalized with hyperkalaemia (HK) and chronic kidney disease (CKD) are at very high risk of HK recurrence, which often requires hospital re-admission [1]. Recurrent HK events have a significant impact on healthcare resource utilization (HCRU) and costs [2]. Several approaches, such as reduction in dietary potassium (K+), reduction or discontinuation of diuretic and renin-angiotensin-aldosterone system inhibitor (RAASi), or oral K+ binders may be used to manage HK in the outpatient setting. Sodium zirconium cyclosilicate (SZC) is an orally administered, non-absorbed, highly selective K+ binder approved for the treatment of HK in adults. In phase 3 trials, after achieving normokalaemia (NK), individualized once-daily SZC therapy maintained normal range serum K+ levels for up to 1 year in adult outpatients [3]. However, it is unknown if SZC prevents HK recurrence compared with standard of care (SoC). Here, we present the rationale and design of the phase 4 CONTINUITY study (D9480C00023), which will compare the efficacy of continued SZC treatment, as part of the post-discharge medication regimen, with SoC, in maintaining NK and reducing HK-related hospital admissions and emergency department (ED) visits. METHOD CONTINUITY is a randomized controlled, open-label, parallel-group, multicentre study in participants with CKD treated for HK while in hospital, to be conducted in 30–50 study sites across four to seven European countries. The study will comprise both an in-hospital and an outpatient (post-discharge) phase (Figure). During the in-hospital phase, all participants will be treated with SZC to correct HK (SZC 10 g three times daily, up to 72 h) and maintain NK (SZC from 5 g every other day to 10 g once daily) as per local label for 2–14 days. At discharge, participants with NK established on an SZC maintenance dose will be randomised (1:1) to either SZC per local label (Arm A) or SoC per local practice (Arm B); participants intended to be discharged with a K+ binder will not be randomized and will be discontinued from the study. Following randomization, participants enter the outpatient phase and will be monitored for 180 days post-discharge via seven planned follow-up visits or phone calls, followed by a site visit at 7 days after end of treatment (Figure). Participants will be screened to yield 506 entering the in-hospital phase, resulting in 430 participants discharged and randomized (215 per arm) and 344 evaluable participants. Adults (≥18 years) with stage 3b–5 CKD or eGFR &amp;lt;45 mL/min/1.73 m2 at or within 3 months prior to study screening, who are admitted to hospital with a serum K+ of 5.5–6.5 mmol/L, will be eligible. The primary endpoint is the occurrence of NK (serum K+ 3.5–5.0 mmol/L) at 180 days post-discharge. Secondary and exploratory outcomes assessed within 180 days post-discharge include a composite endpoint of any HK-related hospital admission or ED visit, use of rescue therapy for HK and all-cause death, as well as RAASi treatment status and dose, and K+ level. Safety and tolerability will also be evaluated. CONCLUSION CONTINUITY is the first study to examine the efficacy of extended use of a novel K+ binder post-discharge compared with SoC, on the maintenance of NK and reduced HCRU among patients with HK, with CKD stage 3b–5. This study will address the importance of maintaining NK after discharge in routine clinical practice, and the impact of improved management of patients with CKD and HK.

MO364: Population Pharmacodynamic Dose-Response Analysis of Serum Potassium Following Dosing With Sodium Zirconium Cyclosilicate

Abstract BACKGROUND AND AIMS Sodium zirconium cyclosilicate (SZC, LOKELMA®) is an orally administered suspension for treating hyperkalemia that permits selective, monovalent cation exchange and has a high exchange capacity for potassium cations in the gut leading to a net reduction in systemic potassium. The goals of the analysis were to describe the population pharmacodynamic response of serum potassium concentration (S-K) in hyperkalemic subjects treated with SZC; specifically, the longitudinal dose response of SZC for S-K in correction (0–48 h) and maintenance (&amp;gt;48 h) phases of treatment, and the differences in S-K response among populations identified by their intrinsic and extrinsic factors. METHOD A population pharmacodynamic model was developed using serum potassium, dose timing/amount, and patient demographic and medical history data pooled from 7 phase 2 and 3 clinical studies consisting of 2369 subjects with hyperkalemia (screening S K &amp;gt;5 mmol/L) with a total of 25 764 S-K observations. A virtual pharmacokinetic-pharmacodynamic model (K-PD) model was used to mimic a drug exposure without any measurements (none were available, drug was not absorbed). S-K over time was described by an indirect response model where potassium enters/leaves a compartment corresponding to serum potassium measurements. The impact of SZC exposure was modeled as an inhibition of the potassium production rate, consistent with the SZC mechanism of action to bind potassium and lower its absorption and appearance in circulation. RESULTS Diagnostics indicated good agreement between the observed data and the model, for mean S-K and change from baseline, and overall qualified the model as appropriate for predicting S-K changes following SZC dosing. The sigmoid exposure response on Kin was characterized by a high value for the EC50 (32.8 g) and a hill coefficient of 1.36. Not surprisingly, within the range of doses studied (0–15 g), the dose response appeared nearly linear. The placebo adjusted S-K change from baseline for QD maintenance treatment was 0.37 (95% CI –0.42 to –0.32) for 5 g, –0.75 (95% CI –0.82 to –0.65) for 10 g, and –1.06 (95% CI –1.17 to –0.89) for 15 g. Greater treatment response was associated with high S-K at baseline, more advanced age, lower body weight and lower eGFR. Furthermore, greater treatment response was also predicted for Black or African American and Asian patients, compared with Caucasian individuals, but they remained unworthy of dose adjustment. Lastly, dose-response simulations show no clinically meaningful difference between maintenance regimens of 5 g QOD and 2.5 g QD in the studied patient groups. CONCLUSION The population K-PD model of SZC adequately described the changes in serum potassium concentration during correction and maintenance phase dosing in the seven clinical studies. Greater treatment response was associated with high S-K at baseline, more advanced age, lower body weight, lower eGFR, Black or African American race and Asian race; however, the impact of each covariate was modest. The overall results of this analysis support the conclusion that no dose adjustment is needed for SZC based on any of the tested covariates.