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Background: Inhibitors of the renin–angiotensin–aldosterone system (RAAS), such as ACE inhibitors (ACEi), angiotensin-II receptor blockers and mineralocorticoid receptor antagonists, reduce morbidity and mortality in hypertension, congestive heart failure and chronic kidney disease. However, their use can lead to hyperkalaemia. We examined the proportions of RAAS inhibitor (RAASi) reduction or withdrawal, across GFR strata, following hospitalisation and the effect on patient mortality. Methods: This was a retrospective cohort study of adult patients hospitalised from 1 January2017 to 31 December2020. Biochemistry data, clinical notes and medicines use were extracted using the CogStack platform, from electronic health records. Patients were identified by creatinine measurement during hospitalisation. Hyperkalaemia was defined as potassium > 5.0 mmol/L, with severity categorisation. RAASi discontinuation defined as ≥ 48 h without administration. Mortality risk associated with RAASi cessation was assessed using Cox proportional hazards models. Results: Among 129,172 patients with potassium measurements, 49,011 were hospitalised. Hyperkalaemia prevalence was 8.57% in the emergency department and 16.79% among hospitalised patients. Higher hyperkalaemia levels correlated with increased CKD and heart failure. RAASi use was more common in hyperkalaemic patients, with higher discontinuation rates during hospitalisation (36% with potassium 5–5.5 mmol/L; 61% with potassium > 6.5 mmol/L). By discharge, 32% of patients had RAASi stopped, and 2% doses reduced. Discontinuation of RAASi was associated with 37% worse survival probability. Conclusion: RAASi cessation was greater with hyperkalaemia and associated with increased mortality in hospitalised patients. Reinstitution of RAASi after hospital discharge, or alternative management of hyperkalaemia if maintained on RAASi therapy, may improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Hyperkalaemia is one of the common electrolyte disorders among hospital patients, affected by many risk factors including medications and medical conditions. Prompt treatment is important given its impact on patient mortality and morbidity, which can lead to negative patient outcomes and healthcare resource utilisation. This study aims to describe the prevalence, characteristics, and treatment of patients admitted to hospitals with hyperkalaemia and compare findings between patients with kidney failure on maintenance haemodialysis therapy and patients without kidney failure. It also aims to identify associations between hyperkalaemia and hospital length of stay. Methods: We undertook a retrospective cohort study on adult patients admitted to Townsville University Hospital between 1st January 2018 and 31st December 2022 (n = 99,047). Patients were included if they had a serum potassium result of 5.1 mmol/L and above during their admission/s. Statistical analysis was conducted using several methods. A Welch's t test and Chi-square test were employed to assess differences between groups of patients with kidney failure on maintenance haemodialysis therapy and those without kidney failure. For comparison among multiple groups with varying severities of hyperkalaemia, the Kruskal-Wallis test with Mann-Whitney U test and logistic regression were used. Results: 8,775 hyperkalaemic patients were included in the study, with a mean age of 64.7 years. The prevalence of hyperkalaemia was 8.9% of patients. Risk factors for hyperkalaemia were highly prevalent among those who had the condition during their admissions. Patients with kidney failure on haemodialysis who had hyperkalaemia were, on average, 6 years younger, more often Indigenous, and experienced more severe hyperkalaemia compared to other patients without kidney failure. There was a notable difference in hyperkalaemia treatment between groups with varying degrees of hyperkalaemia severity. Hyperkalaemia was not found to be associated with prolonged hospital stay. Conclusion: Hyperkalaemia is common among hospital admissions. Patients with kidney failure on haemodialysis are at higher risk of developing severe hyperkalaemia. Treatment for hyperkalaemia was variable and likely insufficient. Timely detection and treatment of hyperkalaemia is recommended. [ABSTRACT FROM AUTHOR]

Background Sodium zirconium cyclosilicate (SZC) reduces serum potassium in patients with chronic hyperkalaemia in clinical trials, but its role in the emergency treatment of hyperkalaemia is unproven. We hypothesized that SZC use for emergent hyperkalaemia would be associated with a reduction in rates of emergency interventions for hyperkalaemia. Methods This was a single-centre, propensity score–weighted case–control study of patients admitted with hyperkalaemia to a specialist renal centre. We randomly selected 250 patients admitted between April 2021 and September 2022 (post-SZC era) with a potassium level ≥5.5 mmol/l treated with at least one ≥10 g dose of SZC (treatment group). We randomly selected a comparator group of 250 patients admitted between January 2018 and December 2019 (pre-SZC era) with a potassium level ≥5.5 mmol/l (control group). Baseline demographic and clinical characteristics were recorded and used as covariates for propensity scoring and inverse probability treatment weighting (IPTW). Our primary outcome measure, rates of emergency haemodialysis (HD), was tested using unadjusted models and multivariable logistic regression models on unweighted data in addition to unadjusted models on weighted data. We also reviewed rates of emergency temporary central venous access as a secondary outcome. Results A total of 59% were male, the mean age was 67 years (standard deviation 14) and 149 (30%) were receiving maintenance dialysis. IPTW achieved satisfactory balance of covariates between the treatment and control groups. In the treatment group, patients were 77% less likely to need emergency HD {odds ratio [OR] 0.23 [confidence interval (CI) 0.17–0.31]}. This result was consistent following analysis of weighted and unweighted data. Similarly, patients treated with SZC were 73% less likely to require emergency temporary central venous access [OR 0.27 (CI 0.20–0.36)]. Conclusion SZC was associated with a significant reduction in the rates of emergency HD and emergency temporary central venous access in patients admitted to a specialized renal centre with emergent hyperkalaemia. [ABSTRACT FROM AUTHOR]

Abstract Patients with heart failure (HF), particularly those with impaired renal function receiving renin–angiotensin–aldosterone system inhibitors (RAASis), are at risk of hyperkalaemia; when hyperkalaemia is severe, this can have serious clinical consequences. The incidence, prevalence, and risk factors for hyperkalaemia reported in randomized trials of RAASis may not reflect clinical practice due to exclusion of patients with elevated serum potassium (sK+) or severe renal impairment: information on patients managed in routine clinical care is important to understanding the actual burden of hyperkalaemia. This paper reviews the available clinical epidemiology data on hyperkalaemia in HF and considers areas requiring further research. Observational studies published since 2017 that focused on hyperkalaemia, included patients with HF, and had ≥1000 participants were considered. Hyperkalaemia occurrence in HF varied widely from 7% to 39% depending on the setting, HF severity, follow‐up length, and concomitant medications. Rates were lowest in patients with newly diagnosed HF and highest in patients with greater disease severity; comorbidities, such as chronic kidney disease and diabetes, and RAASi use, reflected commonly identified risk factors for hyperkalaemia in patients with HF. Hyperkalaemia was most often mild; however, from the limited data available, persistence of mild hyperkalaemia was associated with an increased risk of mortality and major adverse cardiovascular events. There were also limited data available on the progression of hyperkalaemia. Recurrence was common, occurring in one‐quarter to two‐fifths of hyperkalaemia cases. Despite HF guidelines recommending close monitoring of sK+, 55–93% of patients did not receive appropriate testing before or after initiation of RAASi or in follow‐up to moderate/severe hyperkalaemia detection. Many of the observational studies were retrospective and from a single country. There is a need for international, prospective, longitudinal, observational studies, such as the CARE‐HK in HF study (NCT04864795), to understand hyperkalaemia's prevalence, incidence, and severity; to identify and characterize cases that persist, progress, and recur; to highlight the importance of sK+ monitoring when using RAASi; and to assess the impact of newer HF therapies and potassium binders in clinical practice. Data from both clinical trials and observational studies with adjustments for confounding variables will be needed to assess the contribution of hyperkalaemia to clinical outcomes.

The management of hypertension in diabetes is crucial in reducing the risk of cardiovascular disease, which is significantly higher than in people without diabetes. This article, the second in a two-part series on diabetes and hypertension, highlights lifestyle change and the use of medication to manage hypertension, with a focus on the need to consider factors affecting individuals. The use of first-line antihypertensive agents with cardiorenal benefits is discussed, along with the building of therapy in situations where comorbidities might direct drug choice. Resistant hypertension and treatment of hypertension in pregnancy are also reviewed. Two case histories are provided to test the reader's knowledge and problem-solving skills. [ABSTRACT FROM AUTHOR]

Hyperkalaemia is associated with prolonged hospital admission and worse mortality. Hyperkalaemia may also necessitate clinical consults, therapies for hyperkalaemia and high-dependency bed utilisation. We evaluated the 'hidden' human and organisational resource utilisation for hyperkalaemia in hospitalised patients. This was a single-centre, observational cohort study (Jan 2017–Dec 2020) at a tertiary-care hospital. The CogStack system (data processing and analytics platform) was used to search unstructured and structured data from individual patient records. Association between potassium and death was modelled using cubic spline regression, adjusted for age, sex, and comorbidities. Cox proportional hazards estimated the hazard of death compared with normokalaemia (3.5–5.0 mmol/l). 129,172 patients had potassium measurements in the emergency department. Incidence of hyperkalaemia was 85.7 per 1000. There were 49,011 emergency admissions. Potassium > 6.5 mmol/L had 3.9-fold worse in-hospital mortality than normokalaemia. Chronic kidney disease was present in 21% with potassium 5–5.5 mmol/L and 54% with potassium > 6.5 mmol/L. For diabetes, it was 20% and 32%, respectively. Of those with potassium > 6.5 mmol/L, 29% had nephrology review, and 13% critical care review; in this group 22% transferred to renal wards and 8% to the critical care unit. Dialysis was used in 39% of those with peak potassium > 6.5 mmol/L. Admission hyperkalaemia and hypokalaemia were independently associated with reduced likelihood of hospital discharge. Hyperkalaemia is associated with greater in-hospital mortality and reduced likelihood of hospital discharge. It necessitated significant utilisation of nephrology and critical care consultations and greater likelihood of patient transfer to renal and critical care. [ABSTRACT FROM AUTHOR]

Background Hyperkalaemia is a barrier to achieving optimal, guideline-directed treatment with renin–angiotensin–aldosterone system inhibitors (RAASis) in patients with chronic kidney disease (CKD) and/or heart failure (HF). This study describes the association between hyperkalaemia-related RAASi treatment reduction and the number of hospitalized days in patients with CKD and/or HF in Sweden and Japan. Methods Using data from health registers and hospital medical records, patients with CKD and/or HF currently receiving RAASis who experienced an index hyperkalaemia episode were identified and categorized as having maintained or reduced RAASi treatment post-index; propensity score matching (1:1) was applied to balance the groups in terms of baseline characteristics. Changes in the number of all-cause, CKD- and HF-related hospitalized days per patient-year during 6 months pre- versus post-index and the number of days alive and out of hospital (DAOH) during 6 months post-index were described. Results Overall, 20 824 and 7789 patients were included from Sweden and Japan, respectively, 42% and 38% of whom reduced their RAASi treatment after the index hyperkalaemia episode. During the 6 months post-index, all-cause hospitalization increased by 18.2 days [95% confidence interval (CI) 17.0–19.2] per person-year in Sweden and 17.9 days (95% CI 17.4–18.5) per person-year in Japan among patients with reduced RAASi treatment compared with increases of 9.4 days (95% CI 8.6–10.4) and 8.5 days (95% CI 8.0–9.0) per person-year, respectively, among patients with maintained RAASi treatment. The mean DAOH was 121.5 [standard deviation (SD) 75.0] in Sweden and 141.7 (SD 54.5) in Japan among patients with reduced RAASi treatment compared with 154.0 (SD 51.3) and 157.5 (SD 31.6), respectively, among patients with maintained RAASi treatment. Conclusion Patients whose RAASi treatment was reduced after a hyperkalaemia episode had more hospitalized days and fewer DAOH compared with patients whose RAASi treatment was maintained. [ABSTRACT FROM AUTHOR]

Patients with heart failure (HF), particularly those with impaired renal function receiving renin–angiotensin–aldosterone system inhibitors (RAASis), are at risk of hyperkalaemia; when hyperkalaemia is severe, this can have serious clinical consequences. The incidence, prevalence, and risk factors for hyperkalaemia reported in randomized trials of RAASis may not reflect clinical practice due to exclusion of patients with elevated serum potassium (sK+) or severe renal impairment: information on patients managed in routine clinical care is important to understanding the actual burden of hyperkalaemia. This paper reviews the available clinical epidemiology data on hyperkalaemia in HF and considers areas requiring further research. Observational studies published since 2017 that focused on hyperkalaemia, included patients with HF, and had ≥1000 participants were considered. Hyperkalaemia occurrence in HF varied widely from 7% to 39% depending on the setting, HF severity, follow‐up length, and concomitant medications. Rates were lowest in patients with newly diagnosed HF and highest in patients with greater disease severity; comorbidities, such as chronic kidney disease and diabetes, and RAASi use, reflected commonly identified risk factors for hyperkalaemia in patients with HF. Hyperkalaemia was most often mild; however, from the limited data available, persistence of mild hyperkalaemia was associated with an increased risk of mortality and major adverse cardiovascular events. There were also limited data available on the progression of hyperkalaemia. Recurrence was common, occurring in one‐quarter to two‐fifths of hyperkalaemia cases. Despite HF guidelines recommending close monitoring of sK+, 55–93% of patients did not receive appropriate testing before or after initiation of RAASi or in follow‐up to moderate/severe hyperkalaemia detection. Many of the observational studies were retrospective and from a single country. There is a need for international, prospective, longitudinal, observational studies, such as the CARE‐HK in HF study (NCT04864795), to understand hyperkalaemia's prevalence, incidence, and severity; to identify and characterize cases that persist, progress, and recur; to highlight the importance of sK+ monitoring when using RAASi; and to assess the impact of newer HF therapies and potassium binders in clinical practice. Data from both clinical trials and observational studies with adjustments for confounding variables will be needed to assess the contribution of hyperkalaemia to clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70–95%]) than MRA (20% [10–30%]), SGLT2i (30% [20–50%]) or (GLP1-RA (10% [5–15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15–40%) vs 18% [10%–25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5–5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers’ dosage reduction was the usual management.

Roundup (41% glyphosate and 15% poly oxy ethylene amine, POEA surfactant) is a common herbicide used by famers in India. Its cause of poisoning is mostly suicidal, consumed by oral route. Acute poisoning involves gastro intestinal system, respiratory system, renal and cardiovascular system. Glyphosate and its surfactant (POEA) cause hyperkalaemia, metabolic acidosis and cardiac arrest which is the main cause of mortality associated with poisoning. Treatment involves supportive care in high dependency units as there is no specific antidote available.1,2. We report three cases of herbicide poisoning managed in critical care unit. [ABSTRACT FROM AUTHOR]

Inpatient treatment of hyperkalaemia with insulin and dextrose can be complicated by iatrogenic hypoglycaemia. We sought to assess the incidence of hypoglycaemia in hospitalised patients with renal disease and assess the impact of the introduction of a local guideline incorporating the use of sodium zirconium cyclosilicate (SZC) for patients with moderate hyperkalaemia. After establishing a significant burden of hypoglycaemia in the initial observation period, a requirement for hourly capillary blood glucose monitoring (for up to 6 h) following the administration of insulin for hyperkalaemia was incorporated into the guidelines. The two-fold introduction of SZC alongside changes in patient care after the administration of insulin/dextrose resulted in more appropriate use of insulin/dextrose, as well as a significant (73%) reduction in the iatrogenic burden of hypoglycaemia (P = 0.04). [ABSTRACT FROM AUTHOR]

This case study describes a male domestic shorthair cat with urethral obstruction (UO). The cat was catheterised by its primary care practice, hospitalised for the day and then transferred to the out-of-hours (OOH) provider. On admission of the patient, a urine collection set was in place with the clamp closed, which occluded the urine flow. There was no evidence of urine in the system, despite it having been placed several hours previously. The patient was stuporous and had severe metabolic acidosis, and was given a grave prognosis. Unfortunately, due to the patient's critical condition and financial constraints, it was euthanased within 1 hour of admission. The case highlights the importance of continuity of care when transferring patients to an OOH service. Key nursing points include a focus on metabolic acidosis and the monitoring of trends, and fluid therapy and the effect it can have on acidaemia in these cases. It also highlights the role of the veterinary nurse in monitoring patients with UO. [ABSTRACT FROM AUTHOR]

Introduction: Hyperkalaemia (HK) is prevalent among patients with chronic kidney disease (CKD) and chronic heart failure, especially if they are treated with renin‐angiotensin‐aldosterone system inhibitors (RAASi). This study evaluated the cost‐effectiveness of a newly developed anti‐HK therapy, sodium zirconium cyclosilicate (SZC), to the current standard of care for treating HK in advanced CKD patients from the Singapore health system perspective. Methods: We adapted a global microsimulation model to simulate individual patients' potassium level trajectories with baseline potassium ≥5.5 mmol/L, CKD progression, changes in treatment, and other fatal and non‐fatal events. Effectiveness data was derived from ZS‐004 and ZS‐005 trials. Model parameters were localised using CKD patients' administrative and medical records at the Singapore General Hospital Department of Renal Medicine. We estimated the lifetime cost and quality‐adjusted life years (QALYs) of each HK treatment, and the incremental cost‐effectiveness ratio of SZC. Results: SZC demonstrated cost‐effectiveness with an incremental cost‐effectiveness ratsio of SGD 45 068 per QALY over a lifetime horizon, below the willingness‐to‐pay threshold of SGD 90 000 per QALY. Notably, SZC proved most cost‐effective for patients with less severe CKD who were concurrently using RAASi. Sensitivity analyses confirmed the robustness of the findings, accounting for alternative parameter values and statistical uncertainty. Conclusion: This study establishes the cost‐effectiveness of SZC as a treatment for HK, highlighting its potential to mitigate the risk of hyperkalaemia and optimise RAASi therapy. These findings emphasise the value of integrating SZC into the Singapore health system for improved patient outcomes and resource allocation. Summary at a glance: The use of sodium zirconium cyclosilicate (SZC) can potentially lower the risk of hyperkalaemia among patients with chronic kidney disease and facilitate the optimization of RAASi therapy. This study demonstrated the incremental cost‐effectiveness of SZC relative to usual care (sodium polystyrene sulfonate) from the Singapore healthcare system perspective. [ABSTRACT FROM AUTHOR]

Background This observational cohort study compared the likelihood of maintained (stabilized/up-titrated) renin–angiotensin–aldosterone system inhibitor (RAASi) therapy at 6 months following hyperkalaemia in patients with chronic kidney disease (CKD) and/or heart failure (HF) from the USA, Japan and Spain who received sodium zirconium cyclosilicate (SZC) for at least 120 days, relative to those with no prescription for a potassium (K+) binder. Methods Using health registers and hospital medical records, patients with CKD and/or HF receiving RAASi therapy who experienced a hyperkalaemia episode were identified. Propensity score (PS) matching (1:4) was applied to balance the SZC cohort to the no K+ binder cohort on baseline characteristics. Logistic regression analysis was performed to compare the odds of maintained RAASi therapy at 6 months in the SZC versus no K+ binder cohorts. Results The PS-matched SZC cohort included 565 (USA), 776 (Japan) and 56 (Spain) patients; the no K+ binder cohort included 2068, 2629 and 203 patients, respectively. At 6 months, 68.9% (USA), 79.9% (Japan) and 69.6% (Spain) in the SZC cohorts versus 53.1% (USA), 56.0% (Japan) and 48.3% (Spain) in the no K+ binder cohorts had maintained RAASi therapy. Meta-analysed across countries, the odds ratio of maintained RAASi therapy in the SZC cohort versus no K+ binder cohort was 2.56 (95% confidence interval 1.92–3.41; P  < .0001). Conclusions In routine clinical practice across three countries, patients treated with SZC were substantially more likely to maintain guideline-concordant RAASi therapy at 6 months following hyperkalaemia relative to patients with no K+ binder treatment. [ABSTRACT FROM AUTHOR]

Potassium (K) is an essential mineral that is necessary for normal cell and membrane function and for maintaining both fluid balance and acid-base balance. Potassium is furthermore very important for normal excitation, for example in nerves and muscle. It is widely available in several food products, with the most important dietary sources being potatoes, fruits, vegetables, cereal and cereal products, milk and dairy products, and meat and meat products. Potassium deficiency and toxicity is rare in healthy people, but dietary potassium is associated with other health outcomes. Results from observational studies have shown that a potassium intake above 3500 mg/day (90 mmol/day) is associated with a reduced risk of stroke. Similarly, intervention studies provide evidence that this level of potassium intake has a beneficial effect on blood pressure, particularly among persons with hypertension and in persons with a high sodium intake (>4 g/day, equivalent to >10 g salt/day).

Abstract Guideline‐directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin–angiotensin–aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta‐analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed‐effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02–1.25), P = 0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57–0.90), P = 0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24–0.72), P = 0.002]. However, there was no difference between NPB and placebo regarding angiotensin‐converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89–1.17), P = 0.76] and serum potassium change [MD: −0.31 with 95% CI (−0.61 to 0.00), P = 0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12–2.21), P = 0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head‐to‐head comparisons of NPB (patiromer and sodium zirconium cyclosilicate).

Aims: To perform dose–exposure–response analyses to determine the effects of finerenone doses. Materials and Methods: Two randomized, double‐blind, placebo‐controlled phase 3 trials enrolling 13 026 randomized participants with type 2 diabetes (T2D) from global sites, each with an estimated glomerular filtration rate (eGFR) of 25 to 90 mL/min/1.73 m2, a urine albumin‐creatinine ratio (UACR) of 30 to 5000 mg/g, and serum potassium ≤ 4.8 mmol/L were included. Interventions were titrated doses of finerenone 10 or 20 mg versus placebo on top of standard of care. The outcomes were trajectories of plasma finerenone and serum potassium concentrations, UACR, eGFR and kidney composite outcomes, assessed using nonlinear mixed‐effects population pharmacokinetic (PK)/pharmacodynamic (PD) and parametric time‐to‐event models. Results: For potassium, lower serum levels and lower rates of hyperkalaemia were associated with higher doses of finerenone 20 mg compared to 10 mg (p < 0.001). The PK/PD model analysis linked this observed inverse association to potassium‐guided dose titration. Simulations of a hypothetical trial with constant finerenone doses revealed a shallow but increasing exposure–potassium response relationship. Similarly, increasing finerenone exposures led to less than dose‐proportional increasing reductions in modelled UACR. Modelled UACR explained 95% of finerenone's treatment effect in slowing chronic eGFR decline. No UACR‐independent finerenone effects were identified. Neither sodium‐glucose cotransporter‐2 (SGLT2) inhibitor nor glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) treatment significantly modified the effects of finerenone in reducing UACR and eGFR decline. Modelled eGFR explained 87% of finerenone's treatment effect on kidney outcomes. No eGFR‐independent effects were identified. Conclusions: The analyses provide strong evidence for the effectiveness of finerenone dose titration in controlling serum potassium elevations. UACR and eGFR are predictive of kidney outcomes during finerenone treatment. Finerenone's kidney efficacy is independent of concomitant use of SGLT2 inhibitors and GLP‐1RAs. [ABSTRACT FROM AUTHOR]

A young adult, crossbreed dog was presented to a referral small animal veterinary hospital with uroabdomen causing a severe hyperkalaemia. Stabilisation of the condition consisted of abdominocentesis and intravenous administration of calcium gluconate, insulin, glucose and crystalloids. The patient was then anaesthetised for diagnostic and therapeutic procedures. An epidural was performed with levobupivacaine due to nociception and requirement for exploratory surgery. Marked bradycardia ensued and was treated with anticholinergics and terbutaline, among other repeated efforts to resolve a pharmaceutically resistant hyperkalaemia. However, cardiorespiratory arrest followed, characterised by ventricular fibrillation. Cardiopulmonary resuscitation utilised cardioversion to achieve return of spontaneous circulation within 16 minutes. After return of spontaneous circulation, serum potassium levels only decreased and remained below 7 mmol/L after repeat abdominocentesis, alongside continued medical therapy. Unfortunately, despite successful recovery from general anaesthesia, the patient later developed surgical wound dehiscence and was euthanased as a result. [ABSTRACT FROM AUTHOR]

Voltage‐gated Na+ channels are crucial to action potential propagation in excitable tissues. Because of the high amplitude and rapid activation of the Na+ current, voltage‐clamp measurements are very challenging and are usually performed at room temperature. In this study, we measured Na+ current voltage‐dependence in stem cell‐derived cardiomyocytes at physiological temperature. While the apparent activation and inactivation curves, measured as the dependence of current amplitude on voltage, fall within the range reported in previous studies, we identified a systematic error in our measurements. This error is caused by the deviation of the membrane potential from the command potential of the amplifier. We demonstrate that it is possible to account for this artifact using computer simulation of the patch‐clamp experiment. We obtained surprising results through patch‐clamp model optimization: a half‐activation of −11.5 mV and a half‐inactivation of −87 mV. Although the half‐activation deviates from previous research, we demonstrate that this estimate reproduces the conduction velocity dependence on extracellular potassium concentration. Key points: Voltage‐gated Na+ currents play a crucial role in excitable tissues including neurons, cardiac and skeletal muscle.Measurement of Na+ current is challenging because of its high amplitude and rapid kinetics, especially at physiological temperature.We have used the patch‐clamp technique to measure human Na+ current voltage‐dependence in human induced pluripotent stem cell‐derived cardiomyocytes.The patch‐clamp data were processed by optimization of the model accounting for voltage‐clamp experiment artifacts, revealing a large difference between apparent parameters of Na+ current and the results of the optimization.We conclude that actual Na+ current activation is extremely depolarized in comparison to previous studies.The new Na+ current model provides a better understanding of action potential propagation; we demonstrate that it explains propagation in hyperkalaemic conditions. [ABSTRACT FROM AUTHOR]

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Background Sodium zirconium cyclosilicate (SZC), a novel drug used for treating hyperkalaemia, is effective in reducing serum potassium levels. The effects of potassium adsorbents on the mortality and hyperkalaemia-associated hospitalisation rates remain unclear. We aimed to examine how mortality and hyperkalaemia-associated hospitalisation rates vary with usage of various potassium adsorbents. Methods This retrospective study used patients' data between April 2008 and August 2021 obtained from a large-scale Japanese medical claims database. Consecutive patients with chronic kidney disease (CKD) prescribed potassium adsorbents were enrolled and divided into three groups according to the adsorbent type [SZC, calcium polystyrene sulfonate (CPS), and sodium polystyrene sulfonate (SPS)] and were observed for 1 year. The primary outcome was a composite of mortality and hyperkalaemia-associated hospitalisation. Results In total, 234, 54 183, and 18 692 patients were prescribed SZC, CPS, and SPS, respectively. The SZC group showed a higher event-free survival rate than the other two groups. The hazard ratio for the primary outcome in the CPS and SPS groups was similar in the analyses of the subgroups of patients who did not receive renal replacement therapy and those who received haemodialysis. The SZC group had a higher renin-angiotensin-aldosterone system inhibitors (RAASi) continuation rate compared to CPS and SPS groups, the difference being especially significant for SPS. Conclusions This real-world study demonstrated the therapeutic effect of SZC in reducing mortality and hyperkalaemia-associated hospitalisations. The high RAASi continuation rate in the SZC group might be a contributing factor for improvement of the primary outcome. [ABSTRACT FROM AUTHOR]

Guideline‐directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin–angiotensin–aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta‐analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed‐effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02–1.25), P = 0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57–0.90), P = 0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24–0.72), P = 0.002]. However, there was no difference between NPB and placebo regarding angiotensin‐converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89–1.17), P = 0.76] and serum potassium change [MD: −0.31 with 95% CI (−0.61 to 0.00), P = 0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12–2.21), P = 0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head‐to‐head comparisons of NPB (patiromer and sodium zirconium cyclosilicate). [ABSTRACT FROM AUTHOR]

Inpatient treatment of hyperkalaemia with insulin and dextrose can be complicated by iatrogenic hypoglycaemia. We sought to assess the incidence of hypoglycaemia in hospitalised patients with renal disease and assess the impact of the introduction of a local guideline incorporating the use of sodium zirconium cyclosilicate (SZC) for patients with moderate hyperkalaemia. After establishing a significant burden of hypoglycaemia in the initial observation period, a requirement for hourly capillary blood glucose monitoring (for up to 6 h) following the administration of insulin for hyperkalaemia was incorporated into the guidelines. The two-fold introduction of SZC alongside changes in patient care after the administration of insulin/dextrose resulted in more appropriate use of insulin/dextrose, as well as a significant (73%) reduction in the iatrogenic burden of hypoglycaemia (P = 0.04).

Salinomycin, belonging to ionophore antibiotics, has been used as a feed additive for poultry for its coccidiostatic effect. Poisoning by ionophore antibiotics has been reported in cattle and other sensitive animals due to the replacement of medicated feed and/or accidental overdoses. The aim of this paper is to report the toxicity of salinomycin for fallow deer and to describe the different levels of sensitivity of cervids to this substance. In the presented case study, a medicated feed containing ivermectin used for deworming red deer and fallow deer was accidentally contaminated with sodium salinomycinate in a concentration of 252.6 mg/kg. The contaminated feed was consumed by the animals over a period of four days. The mortality of fallow deer within 12 days was 58%. No mortality was recorded in the red deer. In the affected animals, clinical signs associated with acute and congestive heart failure were observed. The biochemical examination indicated prerenal azotaemia caused by circulatory insufficiency and ion imbalance. The histological examination revealed pronounced focal acute cardiomyopathy and massive subacute myopathy in the skeletal muscles.

Resumen: La hiperpotasemia es una alteración electrolítica frecuente con consecuencias potencialmente graves a corto, medio y largo plazo, tanto en términos de morbilidad y mortalidad como de consumo de recursos del Sistema Nacional de Salud. El abordaje de la hiperpotasemia por diversas especialidades médicas y la reciente disponibilidad de nuevos tratamientos farmacológicos específicos hace necesaria una acción unificada y actualizada. El presente documento de consenso entre las sociedades científicas más directamente implicadas en el abordaje de la hiperpotasemia (Sociedad Española de Cardiología, Sociedad Española de Endocrinología y Nutrición, Sociedad Española de Medicina Interna, Sociedad Española de Medicina de Urgencias y Emergencias y Sociedad Española de Nefrología) repasa, en primer lugar, aspectos básicos del balance de potasio y de la potasemia, centrándose posteriormente en el concepto, epidemiología, fisiopatología, y abordaje diagnóstico y terapéutico de la hiperpotasemia. Se han revisado las evidencias y los principales estudios publicados con el objetivo de que sea una herramienta útil en el abordaje multidisciplinar del paciente con hiperpotasemia. Abstract: Hyperkalaemia is a common electrolyte imbalance with potentially serious short-, medium- and long-term consequences on morbidity and mortality rates and the use of national health service resources. The fact that different medical specialities can manage hyperkalaemia makes it important to have a unified approach, and the recent availability of new specific drug treatments means that the approach needs to be updated. This consensus document from the scientific societies most directly involved in the management of hyperkalaemia (Sociedad Española de Cardiología [Spanish Society of Cardiology], Sociedad Española de Endocrinología y Nutrición [Spanish Society of Endocrinology and Nutrition], Sociedad Española de Medicina Interna [Spanish Society of Internal Medicine], Sociedad Española de Medicina de Urgencias y Emergencias [Spanish Society of Emergency Medicine and Emergencies] and Sociedad Española de Nefrología [Spanish Society of Nephrology]) first of all reviews basic aspects of potassium balance and blood potassium. Then it goes on to focus on the concept, epidemiology, pathophysiology and diagnostic and therapeutic approaches to hyperkalaemia. The available evidence and the main published studies have been reviewed with the aim of providing a useful tool in the multidisciplinary approach to patients with hyperkalaemia.

Valproate is known to disturb the kidney function, and high doses or prolonged intake may cause serum ion imbalance, kidney tubular acidosis, proteinuria, hyperuricosuria, polyuria, polydipsia, and dehydration. The aim of this in vivo study was to see whether naringin would counter the adverse effects of high-dose valproate in C57Bl/6 mice and to which extent. As expected, valproate (150 mg/kg bw a day for 10 days) caused serum hyperkalaemia, more in male than female mice. Naringin reversed (25 mg/kg bw a day for 10 days) the hyperkalaemia and activated antioxidative defence mechanisms (mainly catalase and glutathione), again more efficiently in females. In males naringin combined with valproate was not as effective and even showed some prooxidative effects.

Abstract Background Hyperkalaemia is a known risk factor for cardiac arrhythmia and mortality in patients on haemodialysis. Despite standard adequate haemodialysis, hyperkalaemia is common in patients with end-stage renal disease (ESRD) at interdialytic intervals. Data on hyperkalaemia burden and its effects on dialysis patterns and serum potassium (sK) fluctuations in patients on haemodialysis in China remain limited. The prospective, observational cohort study (PRECEDE-K; NCT04799067) investigated the prevalence, recurrence, and treatment patterns of hyperkalaemia in Chinese patients with ESRD on haemodialysis. Methods Six hundred adult patients were consecutively enrolled from 15 secondary and tertiary hospitals in China. In this interim analysis, we report the baseline characteristics of the cohort, the prevalence of predialysis hyperkalaemia (sK > 5.0 mmol/L), and the trends in serum–dialysate potassium gradient and intradialytic sK shift at Visit 1 (following a long interdialytic interval [LIDI]). Results At baseline, most patients (85.6%) received three-times weekly dialysis; mean duration was 4.0 h. Mean urea reduction ratio was 68.0% and Kt/V was 1.45; 60.0% of patients had prior hyperkalaemia (previous 6 months). At Visit 1, mean predialysis sK was 4.83 mmol/L, and 39.6% of patients had hyperkalaemia. Most patients (97.7%) received a dialysate potassium concentration of 2.0 mmol/L. The serum–dialysate potassium gradient was greater than 3 mmol/L for over 40% of the cohort (1–

Salinomycin, belonging to ionophore antibiotics, has been used as a feed additive for poultry for its coccidiostatic effect. Poisoning by ionophore antibiotics has been reported in cattle and other sensitive animals due to the replacement of medicated feed and/or accidental overdoses. The aim of this paper is to report the toxicity of salinomycin for fallow deer and to describe the different levels of sensitivity of cervids to this substance. In the presented case study, a medicated feed containing ivermectin used for deworming red deer and fallow deer was accidentally contaminated with sodium salinomycinate in a concentration of 252.6 mg/kg. The contaminated feed was consumed by the animals over a period of four days. The mortality of fallow deer within 12 days was 58%. No mortality was recorded in the red deer. In the affected animals, clinical signs associated with acute and congestive heart failure were observed. The biochemical examination indicated prerenal azotaemia caused by circulatory insufficiency and ion imbalance. The histological examination revealed pronounced focal acute cardiomyopathy and massive subacute myopathy in the skeletal muscles. [ABSTRACT FROM AUTHOR]

Objectives: This study seeks to determine the association between kidney failure and heart diseases by examining how they influence the diagnosis of hyperkalemia. Methods: We employ a fuzzy regression discontinuity design (RDD) by harnessing the inherent threshold in potassium levels, which serves as a diagnostic criterion for hyperkalemia. Simultaneously, we utilize patient diagnosis data related to kidney failure and heart diseases. This approach allows us to evaluate the causal impact of both diagnoses on hyperkalemia. Results: Significant overall increases in the risk of developing hyperkalemia are evident subsequent to a diagnosis of kidney failure or heart disease. The study finds that the probability of receiving a kidney failure diagnosis increases by 11.2% regarding a cut-off of 6 mEq/L of potassium. In addition, there is a 6.8% likelihood of experiencing hyperkalemia in the case of a prior diagnosis of hypertension, and an 8.8% probability in the case of a diagnosis of depression. The findings remain robust when considering alternative parametric and non-parametric specifications as well as placebo tests. Conclusions: This study provides new empirical insights into the causal impact of kidney failure and heart disease, underscoring the significance of monitoring such patients to prevent serious complications in the future. [ABSTRACT FROM AUTHOR]

Potassium dysregulation can be life-threatening. Dietary potassium modification is a management strategy for hyperkalaemia. However, a 2017 review for clinical guidelines found no trials evaluating dietary restriction for managing hyperkalaemia in chronic kidney disease (CKD). Evidence regarding dietary hyperkalaemia management was reviewed and practice recommendations disseminated. A literature search using terms for potassium, hyperkalaemia, and CKD was undertaken from 2018 to October 2022. Researchers extracted data, discussed findings, and formulated practice recommendations. A consumer resource, a clinician education webinar, and workplace education sessions were developed. Eighteen studies were included. Observational studies found no association between dietary and serum potassium in CKD populations. In two studies, 40–60 mmol increases in dietary/supplemental potassium increased serum potassium by 0.2–0.4 mmol/L. No studies examined lowering dietary potassium as a therapeutic treatment for hyperkalaemia. Healthy dietary patterns were associated with improved outcomes and may predict lower serum potassium, as dietary co-factors may support potassium shifts intracellularly, and increase excretion through the bowel. The resource recommended limiting potassium additives, large servings of meat and milk, and including high-fibre foods: wholegrains, fruits, and vegetables. In seven months, the resource received > 3300 views and the webinar > 290 views. This review highlights the need for prompt review of consumer resources, hospital diets, and health professionals' knowledge. [ABSTRACT FROM AUTHOR]

• Hyperkalaemia is associated with increased mortality risk in patients with chronic heart failure. • Rapid changes in plasma potassium could be considered both a risk factor or a risk marker for increased mortality in patients with heart faliure. • It is essential to avoid overcorrection of hyperkalaemia and thereby risk patients getting hypokalaemic or borderline hypokalaemic. • The optimal plasma-potassium level is 4.7 mmol/L in patients with chronic HF. There is an increasing prevalence of chronic heart failure (HF). It is well known that patients with HF and disturbances in the potassium level have an increased mortality risk. The aim of this study was to investigate the prognosis of a second plasma-potassium measurement after an episode with hyperkalaemia on short-term mortality in patients with chronic HF. From Danish national registers, 2,339 patients with chronic HF and hyperkalaemia (>4.6 mmol/L) at first potassium measurement within 14–365 days from concomitant treatment were identified. To be included, a second measurement was required within 6–30 days subsequent to the first measurement and the 60-day mortality was observed. Based on the second measurement, the patients were divided into five groups: <3.5 mmol/L (n = 257), 3.5–4.0 mmol/L (n = 709), 4.1–4.6 mmol/L (n = 1,204, reference), 4.7–5.0 mmol/L (n = 89) and >5.0 mmol/L (n = 80). To assess all-cause and cardiovascular mortality, we used the Cox regression model. The multivariable analysis showed that patients with potassium concentrations <3.5 mmol/L (hazard ratio (HR): 3.03; 95% CI: 2.49–3.70) and 3.5–4.0 mmol/L (HR: 1.81; 95% CI: 1.54–2.14) had a worse prognosis compared to the reference. We observed similar results when calculating the risk of cardiovascular mortality. A restricted cubic spline curve showed a U-shaped relationship between plasma-potassium and all-cause mortality. Patients with chronic HF and hyperkalaemia who became hypokalaemic after 6–30 days were associated with a higher 60-day all-cause and cardiovascular mortality compared to the reference. This also applied for patients with low normal potassium concentrations (3.5–4.0 mmol/L). [ABSTRACT FROM AUTHOR]

Background: Hyperkalaemia is managed in the emergency department (ED) following measurement of potassium results by blood gas analysers (BGA) or laboratory analysers (LAB). Aims: To determine the prevalence of clinically significant differences between BGA and LAB potassium results and the impact on ED hyperkalaemia management. Methods: Retrospective analysis of time‐matched ED BGA and LAB potassium samples from 2019 to 2020 (taken within 15 min, one or both results ≥6.0 mmol/L). Mean differences and 95% limits of agreement (LoA) were determined for pairs with one or both results ≥6.0 mmol/L and a separate 500 consecutive sample pairs. Results: Four hundred eighty‐eight matched BGA and LAB samples met the inclusion criteria. Of these, 201 (41.2%) differed by ≤0.5 mmol/L, 169 (34.6%) included a haemolysed LAB sample, and 12 (2.5%) had an unreportable BGA sample. One hundred six (21.7%) pairs differed by >0.5 mmol/L, and 60/106 (57%) had normal LAB potassium results, but BGA indicated moderate/severe hyperkalaemia (two of these pairs received hyperkalaemia treatment). Of patients with a haemolysed LAB sample, or where pairs differed by >0.5 mmol, 48 were treated with insulin and five (10.4%) experienced hypoglycaemia. Mean differences and LoA for pairs with LAB results <6.0 mmol/L but BGA ≥6.0 mmol/L demonstrated unacceptable agreement, with 18 (25.7%) BGA results exceeding 8.0 mmol/L. Conclusions: Potentially significant discordance may occur between BGA and LAB potassium results. Clinicians need to be aware of factors impacting both analytical methods' accuracy (such as poor venepuncture or sample handling, (K) EDTA interference) and undetectable haemolysis with BGA measurements. We recommend BGA hyperkalaemia be confirmed with LAB results using a non‐haemolysed sample where time permits. [ABSTRACT FROM AUTHOR]

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Anaesthesiologie & Intensivmedizin is the property of DGAI e.V. - Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin e.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Accurate potassium measurements are necessary for effective clinical management of hyperkalaemia. Pre-analytical factors may affect laboratory measurements, leading to erroneous results and inappropriate patient management and negatively impact the efficiency and finances of laboratories and hospitals. Objective: This study evaluated the impact of rejected potassium test requests on laboratory service. Methods: We conducted a retrospective descriptive study to assess potassium test data at a public laboratory in Pretoria, Gauteng, South Africa, using samples collected from an academic hospital, peripheral hospitals, and outpatient clinics between January 2018 to December 2018. We assessed the relationship between reasons for rejection and health facility type, as well as financial implications for the laboratory. Results: The potassium result rejection rate was 15.1% (29 806 samples), out of the 197 405 requests received. The most common reasons for rejection were old sample ( 1 day old) (41.4%; 12 348 rejections) and haemolysis (38.2%; 11 398 rejections). The most frequent reason for rejections at the central, academic hospital was haemolysis (42.0%), while old sample was the most common reason for rejection at peripheral hospitals (43.4%; 4119/9493 requests) and outpatient health facilities (57.2%; 7208/12 605 requests) (p = 0.022). The total cost of potassium sample rejection over the study period was substantial, given the resource constraints in this setting. Conclusion: Peripheral hospitals and outpatient departments accounted for the majority of rejected potassium testing results, possibly resulting from delays in transportation; causing substantial financial impact on the laboratory. Improved sample collection, handling, and expedited transportation are recommended. What this study adds: This study highlights the importance of appropriate sample collection and handling and the undesirable consequences of non-adherence to these pre-analytical considerations.

Purpose of reviewMedications used frequently after kidney transplantation, including calcineurin inhibitors, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers and antimicrobials, are considered the leading culprit for posttransplant hyperkalaemia in recipients with a well functioning allograft. Other risk factors include comorbidities such as diabetes, hypertension and heart failure; and consumption of a potassium-enriched diet. We review the mechanisms for hyperkalaemia following kidney transplantation that are addressed using nonpharmacological and pharmacological interventions. We also discuss emerging therapeutic approaches for the management of recurrent hyperkalaemia in solid organ transplantation, including newer potassium binding therapies.Recent findingsPatiromer and sodium zirconium cyclosilicate are emerging potassium binders approved for the treatment of hyperkalaemia. Patiromer is a polymer that exchanges potassium for calcium ions. In contrast, sodium zirconium cyclosilicate is a nonpolymer compound that exchanges potassium for sodium and hydrogen ions. Both agents are efficacious in the treatment of chronic or recurrent hyperkalaemia and may result in fewer gastrointestinal side effects than older potassium binders such as sodium polystyrene sulfonate and calcium polystyrene sulfonate. Large-scale clinical studies have not been performed in kidney transplant patients. Patiromer may increase serum concentrations of tacrolimus, but not cyclosporine. Sodium zirconium cyclosilicate does not appear to compromise tacrolimus pharmacokinetics, although it may have a higher sodium burden.SummaryPatiromer and sodium zirconium cyclosilicate may be well tolerated options to treat asymptomatic hyperkalaemia and have the potential to ease potassium dietary restrictions in kidney transplant patients by maintaining a plant-dominant, heart-healthy diet. Their efficacy, better tolerability and comparable cost with respect to previously available potassium binders make them an attractive therapeutic option in chronic hyperkalaemia following kidney transplantation.

Chronic kidney disease (CKD) is a non-communicable disease that affects >10% of the general population worldwide; the number of patients affected by CKD is increasing due in part to the rise in risk factors such as obesity, hypertension, and diabetes mellitus. As many studies show, diet can be an important tool for preventing and mitigating the onset of non-communicable diseases. Plant-based diets (PBDs) are those that emphasize the consumption of plant foods and may or may not include small or moderate amounts of animal foods. Recently, these diets have received increasing interest because they have been associated with favourable effects on health and also appear to protect against the development and progression of CKD. PBDs, which are associated with protein restrictions, seem to offer adjunctive advantages in patients with chronic kidney disease, as compared to conventional low-protein diets that include animal proteins. The principal aims of this review are to provide a comprehensive overview of the existing literature regarding the role of plant-based diets and low-protein, plant-based diets in the context of chronic kidney disease. Moreover, we try to clarify the definition of plant-based diets, and then we analyse possible concerns about the use of PBDs in patients with chronic kidney disease (nutritional deficiency and hyperkalaemia risk). Finally, we offer some strategies to increase the nutritional value of plant-based low-protein diets. In the Materials and Methods section, many studies about plant-based diets and low-protein plant-based diets (e.g., the very-low-protein diet and vegan low-protein diet, LPD) in chronic kidney disease were considered. In the Results and Conclusion section, current data, most from observational studies, agree upon the protective effect of plant-based diets on kidney function. Moreover, in patients with advanced CKD, low-protein plant-based options, especially a very-low-protein diet supplemented with heteroanalogues (VLPDs), compared to a conventional LPD appear to offer adjunctive advances in terms of delaying dialysis and mitigating metabolic disturbances. However, further studies are necessary to better investigate the possible metabolic and cardiovascular advantages of plant-based LPDs versus conventional LPDs. [ABSTRACT FROM AUTHOR]

Aim: To describe the prevalence, severity, risk factors, and clinical relevance of electrolyte disturbances and acute kidney injury (AKI) during febrile urinary tract infection (fUTI). Methods: Retrospective observational study of well/fair‐appearing patients between 2 months and 16 years, with no previous relevant medical history, diagnosed with fUTI in the paediatric emergency department (PED) with subsequent microbiological confirmation. Analytical alteration (AA) data were considered: AKI (creatinine elevation × 1.5 the median for age), plasma sodium alteration (≤130 or ≥150 mEq/L), and potassium alteration (≤3 or ≥6 mEq/L). Results: We included 590 patients, 17.8% presented AA (13 hyponatremia, 7 hyperkalaemia, and 87 AKI). No patient presented severe analytic alterations or a higher frequency of symptoms potentially attributable to these alterations (seizures, irritability, or lethargy). Risk factors associated with these AA were clinical dehydration (OR = 3.5 95% CI: 1.04–11.7; p = 0.044) and presenting a temperature >39°C (OR = 1.9 95% CI: 1.14–3.1; p = 0.013). Conclusions: Electrolyte and renal function disturbances are infrequent in the previously healthy paediatric population with a fUTI. If present, they are asymptomatic and not severe. Based on our results, performing systematic blood analysis to rule out AA appears no longer justified, especially in the absence of risk factors. [ABSTRACT FROM AUTHOR]

Gordon's syndrome, also known as pseudohypoaldosteronism type II and familial hyperkalaemic hypertension, is a rare inherited condition characterised by familial hyperkalaemia, normal anion gap hyperchloraemic metabolic acidosis, low renin with normal glomerular filtration rate and hypertension. The outcome of 11 pregnancies in 3 women with Gordon's syndrome is presented and combined with 13 pregnancies in 7 women previously described. Pregnancy in women with Gordon's syndrome appears to be associated with a significant risk of adverse pregnancy outcomes, particularly where there is maternal hypertension preconception. No pregnancy registry exists for Gordon's syndrome. The available data is limited to case reports and small case series and may be affected by bias. A pregnancy registry would be valuable to assist in preconception counselling and management during pregnancy. The goal of this study was to summarise the available cases describing pregnancy outcomes with maternal Gordon's syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Guideline-directed renin-angiotensin-aldosterone system inhibitor (RAASi) therapy is rarely achieved in clinical settings, often due to hyperkalaemia. We assessed the potassium binder, patiromer, on continuation of RAASi therapy in hyperkalaemic patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) in the AMETHYST-DN trial, propensity score-matched to a real-world cohort not receiving patiromer (Salford Kidney Study). Methods: The phase 2, open-label AMETHYST-DN trial (NCT01371747) randomized 304 adults with CKD on RAASi, T2DM, hyperkalaemia (serum potassium [sK+] >5.0 mEq/L), and hypertension to receive patiromer, 8.4–33.6 g/day for 12 months. Patients underwent propensity score matching for systolic blood pressure (BP), heart failure status, and estimated glomerular filtration rate (eGFR), with 321 patients with CKD, T2DM, hyperkalaemia, and on RAASi from a prospective CKD cohort (Salford Kidney Study). Changes in RAASi utilization, sK+, BP, proteinuria, and eGFR during 12-month follow-up were assessed by Mann-Whitney U or χ2 tests. Results: Matching produced 135:135 patients with no significant differences in age, sex, systolic BP, sK+, eGFR, or heart failure status, although differences in diastolic BP remained (p < 0.001). After 12 months, 100% of AMETHYST-DN patients receiving patiromer remained on RAASi therapy, whereas 38.5% of the Salford Kidney Cohort discontinued RAASi (p < 0.001); hyperkalaemia contributed in 16% of patients (42% of RAASi discontinuations). Significantly greater reductions in sK+ and BP, but not proteinuria or eGFR, were observed in AMETHYST-DN, compared with Salford Kidney Study patients (p < 0.05). Conclusions: These results demonstrate the benefit of patiromer for sK+ management to enable RAASi use while revealing beneficial effects on BP. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Industrial Hygiene & Toxicology / Arhiv za Higijenu Rada I Toksikologiju is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Hyperkalaemia is a known risk factor for cardiac arrhythmia and mortality in patients on haemodialysis. Despite standard adequate haemodialysis, hyperkalaemia is common in patients with end-stage renal disease (ESRD) at interdialytic intervals. Data on hyperkalaemia burden and its effects on dialysis patterns and serum potassium (sK) fluctuations in patients on haemodialysis in China remain limited. The prospective, observational cohort study (PRECEDE-K; NCT04799067) investigated the prevalence, recurrence, and treatment patterns of hyperkalaemia in Chinese patients with ESRD on haemodialysis. Methods: Six hundred adult patients were consecutively enrolled from 15 secondary and tertiary hospitals in China. In this interim analysis, we report the baseline characteristics of the cohort, the prevalence of predialysis hyperkalaemia (sK > 5.0 mmol/L), and the trends in serum–dialysate potassium gradient and intradialytic sK shift at Visit 1 (following a long interdialytic interval [LIDI]). Results: At baseline, most patients (85.6%) received three-times weekly dialysis; mean duration was 4.0 h. Mean urea reduction ratio was 68.0% and Kt/V was 1.45; 60.0% of patients had prior hyperkalaemia (previous 6 months). At Visit 1, mean predialysis sK was 4.83 mmol/L, and 39.6% of patients had hyperkalaemia. Most patients (97.7%) received a dialysate potassium concentration of 2.0 mmol/L. The serum–dialysate potassium gradient was greater than 3 mmol/L for over 40% of the cohort (1– < 2, 2– < 3, 3– < 4, and ≥ 4 mmol/L in 13.6%, 45.1%, 35.7%, and 5.2% of patients, respectively; mean: 2.8 mmol/L). The intradialytic sK reduction was 1– < 3 mmol/L for most patients (0– < 1, 1– < 2, 2– < 3, and ≥ 3 mmol/L in 24.2%, 62.2%, 12.8%, and 0.9% of patients, respectively; mean: 1.4 mmol/L). Conclusions: Hyperkalaemia after a LIDI was common in this real-world cohort of Chinese patients despite standard adequate haemodialysis, and led to large serum–dialysate potassium gradients and intradialytic sK shifts. Previous studies have shown hyperkalaemia and sK fluctuations are highly correlated with poor prognosis. Effective potassium-lowering treatments should be evaluated for the improvement of long-term prognosis through the control of hyperkalaemia and sK fluctuations. Trial registration: ClinicalTrials.gov, NCT04799067. [ABSTRACT FROM AUTHOR]

Since the 1950s, sodium polystyrene sulphonate (SPS) has been the dominant cation exchange agent prescribed for hyperkalaemia. Clinicians have had plenty of time to learn of SPS's advantages and limitations. The demands of drug regulatory agencies regarding the incorporation of medications into the market were not so stringent then as they are today, and the efficacy and safety of SPS have been questioned. In recent years, two novel cation exchangers, patiromer and sodium zirconium cyclosilicate, have received (or are in the process of receiving) regulatory approval in multiple jurisdictions globally, after scrutiny of carefully conducted trials regarding their short-term and mid-term efficacy. In this debate, we defend the view that all three agents are likely to have similar efficacy. Harms are much better understood for SPS than for newer agents, but currently there are no data to suggest that novel agents are safer than SPS. Drug choices need to consider costs, access and numbers-needed-to-treat to prevent clinically important events; for potassium exchangers, we need trials directly examining clinically important events. [ABSTRACT FROM AUTHOR]

'Old-generation' potassium (K) binders [i.e. sodium (SPS) and calcium polystyrene sulfonate] are widely used, but with substantial heterogeneity across countries to treat hyperkalaemia (HK). However, there are no randomized data to support their chronic use to manage HK, nor have they been shown to have a renin–angiotensin–aldosterone system inhibitor (RAASi)-enabling effect. These compounds have poor tolerability and an unpredictable onset of action and magnitude of K lowering. Furthermore, SPS may induce fluid overload, owing to the fact that it exchanges K for sodium. Its use has also been associated with colonic necrosis, as emphasized by a black box warning from the US Food and Drug Administration. In contrast, two new K binders, patiromer and sodium zirconium cyclosilicate, have been shown to be safe and well tolerated for chronic management of HK, thereby enabling RAASi optimization, as acknowledged by the latest international cardiorenal guidelines. In view of the lack of reliable evidence regarding the efficacy and safety of the old-generation K binders compared with the placebo-controlled randomized and real-word evidence demonstrating the safety, efficacy and RAASi-enabling effect of the new K binders, clinicians should now use these new K binders to treat HK (primum non nocere !). [ABSTRACT FROM AUTHOR]

Abstract Aims Several patients with heart failure and reduced ejection fraction (HFrEF) do not receive renin–angiotensin–aldosterone system (RAAS) inhibitors at the recommended dose or at all, frequently due to actual or feared hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is an orally administered non‐absorbed intestinal potassium binder proven to lower serum potassium concentrations. Methods and results PRIORITIZE‐HF was an international, multicentre, parallel‐group, randomized, double‐blind, placebo‐controlled study to evaluate the benefits and risks of using SZC to intensify RAAS inhibitor therapy. Patients with symptomatic HFrEF were eligible and randomly assigned to receive SZC 5 g or placebo once daily for 12 weeks. Doses of study medication and RAAS inhibitors were titrated during the treatment period. The primary endpoint was the proportion of patients at 12 weeks in the following categories: (i) any RAAS inhibitor at less than target dose, and no MRA; (ii) any RAAS inhibitor at target dose and no MRA; (ii) MRA at less than target dose; and (iv) MRA at target dose. Due to challenges in participant management related to the COVID‐19 pandemic, the study was prematurely terminated with 182 randomized patients. There was no statistically significant difference in the distribution of patients by RAAS inhibitor treatment categories at 3 months (P = 0.43). The proportion of patients at target MRA dose was numerically higher in the SZC group (56.4%) compared with the placebo group (47.0%). Overall, SZC was well tolerated. Conclusions PRIORITIZE‐HF was terminated prematurely due to COVID‐19 and did not demonstrate a statistically significant increase in the intensity of RAAS inhibitor therapies with the potassium‐reducing agent SZC compared with placebo.

Abstract Aims Hyperkalaemia is observed frequently in heart failure (HF) patients and is associated with an impaired prognosis and underuse of mineralocorticoid receptor antagonists (MRAs). However, the effects of serum potassium on prescription of the full guideline recommended daily dose of 50 mg in real‐world daily practice are unknown. Therefore, we investigated serum potassium and its association with the prescribed MRA dose in a large cohort of chronic HF patients. Methods and results A total of 5346 patients with chronic HF with a left ventricular ejection fraction ≤40% from 34 Dutch outpatient HF clinics between 2013 and 2016 were analysed on serum potassium and MRA (spironolactone and eplenerone) dose. Data were stratified by potassium as a serum potassium level 5.0 mmol/L. Multivariable logistic regression models were used to assess the association between serum potassium and MRA dose and to adjust for potential confounders. Mean serum potassium was 4.4 ± 0.5 mmol/L and hyperkalaemia (serum potassium >5.0 mmol/L) was present in 399 patients (7.5%). MRA was used in 3091 patients (58.1%). Patients with hyperkalaemia significantly less often received ≥100% of the target dose (50 mg) compared with patients with a serum potassium between 4.0–5.0 mmol/L and