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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., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: According to the Centers for Disease Control and Prevention (CDC), diabetes affects approximately 37.3 million individuals in the USA, with another estimated 96 million people having a prediabetic state. Furthermore, one or two out of three adult Americans exhibit metabolic syndrome or an insulin-resistant state, depending on their age group., Summary: Chronic kidney disease (CKD) represents a complication often associated with type II diabetes or the insulin-resistant condition, typically identifiable through proteinuria. Proteinuria serves as both a marker and a contributing factor to kidney damage, and it significantly heightens the risk of cardiovascular (CV) events, including atherosclerosis, heart attacks, and strokes. Renin-angiotensin-aldosterone system inhibitors (RAASis) have demonstrated clinical efficacy in lowering blood pressure, reducing proteinuria, and slowing CKD progression. However, hyperkalemia is a common and serious adverse effect associated with using RAASi., Key Messages: It is imperative to establish personalized management strategies to enable patients to continue RAASi therapy while effectively addressing hyperkalemia risk. Healthcare professionals must be careful not to inadvertently create a low renal perfusion state, which can reduce distal nephron luminal flow or luminal sodium concentration while using RAASi. Nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), such as finerenone, are demonstrated to delay CKD progression and reduce CV complications, all while mitigating the risk of hyperkalemia. Additionally, maintaining a routine monitoring regimen for serum potassium levels among at-risk patients, making dietary adjustments, and considering the adoption of newer potassium-binding agents hold promise for optimizing RAASi therapy and achieving more effective hyperkalemia management., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Hyperkalemia (HK) may result in disruptions of guidelines-concordant renin-angiotensin-aldosterone system inhibitors (RAASi), a standard of care in persons with chronic kidney disease (CKD). Such disruptions-dose reduction or discontinuation-diminish the benefits of RAASi, placing patients at risk of serious events and renal dysfunction. This real-world study evaluated RAASi modifications among patients who initiated sodium zirconium cyclosilicate (SZC) for HK., Methods: Adults (≥ 18 years) initiating outpatient SZC (index date) while on RAASi were identified from a large US claims database (January 2018-June 2020). RAASi optimization (maintain same or up-titration of RAASi dosage), non-optimization (down-titration of RAASi dosage or discontinuation), and persistence were descriptively summarized following index. Predictors of RAASi optimization were assessed using multivariable logistic regression models. Analyses were conducted by subgroups, including patients without end-stage kidney disease (ESKD), with CKD, and with CKD + diabetes., Results: A total of 589 patients initiated SZC during RAASi therapy (mean age 61.0 years, 65.2% male), and 82.7% patients (n = 487) kept RAASi after index (mean follow-up  = 8.1 months). Most patients (77.4%) optimized RAASi therapy after initiating SZC; 69.6% maintained the same dosage while 7.8% had up-titrations. A similar rate of RAASi optimization was observed among subgroups without ESKD (78.4%), with CKD (78.9%), and with CKD + diabetes (78.1%). At 1-year post-index, 73.9% of all patients who optimized RAASi were still on therapy, while only 17.9% of patients who did not optimize therapy were still on a RAASi. Among all patients, predictors of RAASi optimization included fewer prior hospitalizations (odds ratio = 0.79, 95% CI [0.63-1.00]; p < 0.05) and fewer prior emergency department (ED) visits (0.78 [0.63-0.96]; p < 0.05)., Conclusion: Consistent with clinical trial findings, nearly 80% of patients who initiated SZC for HK optimized their RAASi therapy. Patients may require long-term SZC therapy to encourage continuation of RAASi therapy especially after inpatient and ED visits., (© 2023. The Author(s).)

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 <4.0, 4.0 to 5.0 or >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 <4.0 mmol/L (7.7% vs. 9.5% vs. 13.6% respectively, P = 0.0078). In the multivariable regression analyses, patients with hyperkalaemia were significantly less likely to receive ≥100% of the target dose compared with patients with serum potassium 4.0-5.0 mmol/L (OR 0.38, 95% CI 0.15-0.97, P = 0.044). Additionally, a one unit increase in serum potassium was significantly associated with a lower odds of receiving ≥100% of the target dose (OR 0.69, 95% CI 0.49-0.98, P = 0.036)., Conclusions: In this large registry of real-world chronic HF patients, both an increase in serum potassium and hyperkalaemia were associated with a lower odds of receiving the guideline-recommended MRA dose., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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+] &gt;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 &lt; 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 &lt; 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 &lt; 0.05)., Conclusions: These results demonstrate the benefit of patiromer for sK+ management to enable RAASi use while revealing beneficial effects on BP., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Aims: Renin-angiotensin-aldosterone system inhibitors (RAASi) are guideline-recommended therapy for individuals with cardiorenal disease. They are associated with increased risk of hyperkalaemia, a common and life-threatening disorder for this population. RAASi-induced hyperkalaemia often leads to dose reduction or discontinuation, reducing cardiorenal protection. Guideline recommendations differ between specialties for the clinical management of hyperkalaemia. Using a modified Delphi method, we developed consensus recommendations for optimal management of hyperkalaemia in adults with cardiorenal disease., Methods and Results: An international steering group of cardiologists and nephrologists developed 39 statements regarding hyperkalaemia care, including risk factors and risk stratification, prevention, correction, and cross-specialty coordination. Consensus was determined by agreement on an online questionnaire administered to cardiorenal specialists across Europe and North America. The threshold for consensus agreement was established a priori by the steering group at 67%. Across November 2021, 520 responses were received from Canada (n = 50), France (n = 50), Germany (n = 54), Italy (n = 58), Spain (n = 57), the UK (n = 49), and the US (n = 202); 268 from cardiologists and 252 from nephrologists. Twenty-nine statements attained very high agreement (≥90%) and 10 attained high agreement (≥67%-&lt;90%), with strong alignment between cardiologists and nephrologists., Conclusion: A high degree of consensus regarding hyperkalaemia evaluation and management exists among healthcare professionals. Based on high levels of agreement, the steering group derived six key recommendations for hyperkalaemia prevention and management in people with cardiorenal disease. Future studies examining the quality of hyperkalaemia care delivery are required., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: In France, no consensus document on the management of persistent hyperkalaemia is currently available. Variability in clinical practices has been observed., Methods: A consensus statement on the definition and the management of persistent hyperkalaemia was developed by a Delphi panel of French nephrologists between December 2019 (26 voting participants among 40 invited panellists in first round) and June 2020 (20 voting participants among 26 panellists in second round)., Results: Persisting hyperkalaemia not controlled with current treatment strategies may be defined as the occurrence of two or more hyperkalaemia episodes within a year despite the administration of cation-exchange resins or loop diuretics during the same year. Some patient characteristics (diabetes, chronic kidney disease from stage 3B to stage 5 without dialysis, chronic heart failure) are associated with an increased risk of developing persistent hyperkalaemia. There is a medical need for the management of persistent hyperkalaemia in patients treated with renin-angiotensin-aldosterone system inhibitors that is not met by current treatment strategies (including available cation-exchange resins)., Conclusions: The panel expressed a need for new treatment strategies validated by clinical trials., (Copyright © 2021 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Use of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with heart failure (HF) and reduced ejection fraction is associated with functional improvement, an increase in perceived quality of life, a reduction in the probability of cardiovascular death, and a decrease in the number of hospitalizations. Some of these drugs are also efficacious in patients with chronic kidney disease and albuminuria as well as in patients with resistant hypertension. Despite their numerous benefits, RAASi are associated with an increase in incidence of hyperkalemia, especially in patients with concomitant chronic kidney disease. Hyperkalemia is a common electrolyte disorder that is defined as an elevation in plasma concentrations of potassium above 5 mEq/L. It has been related to rehospitalizations, malignant arrhythmias, and an increase in mortality. On the other hand, optimized treatment with RAASi requires progressive dose increases which can in turn entail a greater probability of hyperkalemia. For all of these reasons, it is necessary to establish management and treatment guidelines for these patients. This consensus document arises from this objective. Its recommendations have been developed by a group of ten experts and reviewed by a panel of another ten specialists in the treatment of patients with HF (ten cardiologists and ten internists in total). This document has been endorsed by the Spanish Society of Cardiology (SEC, for its initials in Spanish) and the Spanish Society of Internal Medicine (SEMI, for its initials in Spanish)., (Copyright © 2021 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Potassium is a major intracellular cation in the body, regulating membrane potential of excitable cells, such as cardiomyocytes and skeletal muscle cells. Because the kidney plays a critical role in controlling potassium balance, the elevation in serum potassium levels is one of the most common complications in patients with maintenance hemodialysis (MHD). In addition to reduced renal potassium excretion, the alteration in body potassium distribution owing to comorbid conditions may also contribute to dyskalemia. Besides potassium elimination through hemodialysis in MHD patients, accumulating data indicate the potential importance of extra-renal elimination involving the gastrointestinal system, which can be affected by the inhibitors of the renin-angiotensin-aldosterone system. In this article, the literature on potassium physiology in MHD patients is reviewed with an emphasis on the changes from individuals with normal kidney function. This article also summarizes the findings of recent studies on dietary control, dialysate prescription, and pharmacological therapy., (© 2021 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Aims: In patients with current or a history of hyperkalaemia, treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) is often compromised. Patiromer, a novel potassium (K + ) binder, may improve serum K + levels and adherence to RAASi., Methods: The DIAMOND trial will enroll ∼820 patients with heart failure with reduced ejection fraction (HFrEF; ejection fraction ≤40%). Patients meeting the screening criteria will enter a single-blinded run-in phase where they will be started or continued on a mineralocorticoid receptor antagonist (MRA) titrated to 50 mg/day and other RAASi therapy to ≥50% target dose, and patiromer. Patiromer will be titrated up to a maximum three packs/day (8.4 g/pack) to achieve optimal doses of RAASi without hyperkalaemia. The run-in phase will last up to 12 weeks, following which patients will undergo double-blind randomization in a 1:1 ratio to receive either continued patiromer or placebo (patiromer withdrawal). The primary endpoint is the mean difference in serum K + from randomization between patiromer and placebo arms. Secondary endpoints will include hyperkalaemia events with K + value >5.5 mEq/L, durable enablement of MRA at target dose, investigator-reported adverse events of hyperkalaemia, hyperkalaemia-related clinical endpoints and an overall RAASi use score (using a 0-8-point scale) comprising all-cause death, occurrence of cardiovascular hospitalization or usage of comprehensive heart failure medication., Conclusion: The DIAMOND trial is designed to determine if patiromer can favourably impact K + control in patients with HFrEF with hyperkalaemia or a history of hyperkalaemia leading to RAASi therapy compromise, and in turn improve RAASi use., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Recurrent hyperkalaemia may result in underutilisation of renin-angiotensin-aldosterone system inhibitors. We report an analysis of French data from the PROKALE retrospective study, which assessed the management of recurrent hyperkalaemia in five European countries., Patients and Methods: A retrospective chart review including patients not on dialysis with two or more hyperkalaemia episodes≥5.5 mEq/L documented within a 12-month observation period was performed., Results: In France, 115 physicians (57 nephrologists et 58 cardiologists) participated in the study and 295 patients were studied in this analysis. Mean age was 68 years; 212 patients (71.9%) had chronic kidney disease, 108 (36.6%) had chronic heart failure and 102 (34.6%) had diabetes mellitus. The mean number of documented hyperkalaemic episodes was 2.3. A total of 90 hospitalizations occurred during the observation period, of which 24 (26.7%) were directly related to a hyperkalaemic episode. At the time of the first documented hyperkalaemic episode, measures used for the management of hyperkalaemia included loop diuretics (144 patients [48.8%]), sodium/calcium polystyrene sulphonate (135 patients [45.8%]), a low-potassium diet (31 patients [10.5%]) and sodium bicarbonate (31 patients [10.5%]). Between the two consecutive hyperkalaemic episodes documented, the proportion of patients on renin-angiotensin-aldosterone system inhibitors treatment decreased from 42.4% to 34.6%., Conclusion: Renin-angiotensin-aldosterone system inhibitors treatment interruptions were observed in the setting of recurrent hyperkalaemic episodes. Recurrent hyperkalaemia is a major cause of hospitalizations. More effective strategies for the prevention of recurrent hyperkalaemia are needed., (Copyright © 2021. Published by Elsevier Masson SAS.)

Renin-angiotensin-aldosterone system inhibitors (RAASi) reduce morbidity and mortality in heart failure (HF) with reduced ejection fraction in a dose-dependent manner. They also have a positive impact in other cardiovascular diseases (CVDs). However, RAASi may induce hyperkalemia, a potentially life-threatening disorder. This risk is further increased in those with concomitant chronic kidney disease, diabetes mellitus, and/or in patients with hypertension. Current treatment guidelines recommend maximal RAASi dosing to improve clinical outcomes; however, this is often limited by the development of hyperkalemia. When this occurs, current guidelines recommend RAASi down-titration/interruption, which, while improving short-term prognosis, is associated with a negative long-term prognostic impact. At present, the European Society of Cardiology suggests the consideration of novel potassium binders (patiromer and sodium zirconium cyclosilicate) for the management of RAASi-associated hyperkalemia. Both drugs can reduce serum potassium levels and prevent recurrent hyperkalemia. Additionally, patiromer showed enabling of RAASi optimization in high-risk patients. Nevertheless, precise recommendations on the use of these drugs are lacking. Building upon current HF guideline recommendations, a multidisciplinary expert panel convened to design an algorithm providing practical guidance on the use of novel potassium binders/patiromer in patients with HF and/or other CVD. As a result of that effort, we present an evidence-based treatment algorithm for the management of hyperkalemia with novel potassium binders/patiromer in patients with HF and/or other CVD receiving RAASi, including the necessary monitoring to avoid induction of hypokalemia. This algorithm aims to maintain or up-titrate RAASi to optimized doses, while maintaining normokalemia, improved clinical outcomes, and long-term prognosis.

Introduction : Patients with cardiovascular diseases (CVD) are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone inhibitors (RAASIs). Because the occurrence or fear of hyperkalemia, RAASIs are frequently down-titrated or discontinued in patients with CVD, with consequent worse outcomes than patients who remain on maximum doses. Areas covered : This article reviews potassium homeostasis, epidemiology, risk factors, and outcomes of hyperkalemia, and efficacy and safety of the drugs used for acute and chronic treatment of hyperkalemia. A literature search was carried out using the PubMed and guidelines for the management of hyperkalemia. Expert opinion : The emergency treatment of hyperkalemia is not supported by high-quality evidence and clinical trials did not report drug effects on clinical outcomes. Two potassium binders, patiromer and sodium zirconium cyclosilicate, represent a new approach in the treatment of chronic hyperkalemia as they may allow the titration and maintenance of guidelines-recommended doses of RAASIs in patients with CVD who otherwise would not tolerate them due to the risk of hyperkalemia.Further studies are needed to evaluate the safety and efficacy of drug therapy and support the development of guidelines for acute and chronic hyperkalemia.

Aims: The aims of this study were to evaluate if the risk of cardiovascular events and all-cause mortality was higher in the presence of hyperkalaemia (HK) in patients with heart failure (HF) treated with renin-angiotensin-aldosterone system inhibitors (RAASi), and to investigate in this cohort the increased risk of cardiovascular events and all-cause mortality among HK patients with non-optimal adherence to RAASi therapy., Methods and Results: In this retrospective cohort study based on administrative databases of five Italian Local Health Units, all adult patients with a HF diagnosis between January 2010 and December 2017 were included only if they were prescribed RAASi therapy during the first 3 months after the index date, that corresponded to the date of first HF diagnosis during the inclusion period. Patients were considered to have HK if serum potassium level was ≥5.5 mmol/L. A propensity score matching was applied before evaluation of hazard ratios. Patients with HK were 37% (P < 0.001) and 70% (P < 0.001), respectively, more at risk of cardiovascular events and of dying for all-cause mortality compared to non-HK patients. Among the HK group, patients non-adherent to RAASi therapy had a 39% (P = 0.105) higher risk of cardiovascular events and a twofold increased risk (P < 0.001) of all-cause death., Conclusion: Findings from this real-world study showed that in a cohort of HF patients under RAASi therapy, subjects with HK had an enhanced risk of cardiovascular events or death compared to patients without HK. Moreover, in HK patients, sub-optimal adherence to RAASi therapy was associated with an increased risk of all-cause mortality., (© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction and Objectives: Renin-angiotensin-aldosterone system inhibitors (RAASi) are the cornerstone of treatment of heart failure with reduced ejection fraction (HFrEF). RAASi optimization in real-life care is challenged by hyperkalemia, a potentially fatal adverse event, which can necessitate downtitration or discontinuation of RAASi and negatively impact survival in HFrEF. The literature on this problem is sparse. We performed a systematic review of studies on HFrEF to investigate the prevalence, incidence, and risk factors of hyperkalemia, RAASi prescription rates, frequency of RAASi downtitration or discontinuation due to hyperkalemia, and the potential negative effect of the latter on prognosis., Methods: We conducted a MEDLINE (PubMed) search including observational and interventional studies published between January 1987 and May 2018., Results: A total of 30 observational and 18 interventional studies were included in the review. The incidence of hyperkalemia reported was between 0% and 63% in observational studies and was between 0% and 30% in clinical trials. Risk factors for hyperkalemia included RAASi prescription, older age, diabetes, and chronic kidney disease. In real-life studies, RAASi were downtitrated or discontinued in 3-22% of HFrEF patients; hyperkalemia was the reported cause in 5% of cases. No reports were found on the impact on prognosis of RAASi downtitration or discontinuation due to hyperkalemia., Conclusions: Hyperkalemia and RAASi downtitration or discontinuation are frequent, particularly in real-life HFrEF studies. Further research is needed to clarify the role of RAASi downtitration or discontinuation due to hyperkalemia and to assess its long-term prognostic impact in HFrEF patients., (Copyright © 2020 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aims: We assessed the interplay between hyperkalaemia (HK) and renin-angiotensin-aldosterone system inhibitor (RAASi) use, dose and discontinuation, and their association with all-cause or cardiovascular death in patients with chronic heart failure (HF). We hypothesized that HK-associated increased death may be related to RAASi withdrawal., Methods and Results: The ESC-HFA-EORP Heart Failure Long-Term Registry was used. Among 9222 outpatients (HF with reduced ejection fraction: 60.6%, HF with mid-range ejection fraction: 22.9%, HF with preserved ejection fraction: 16.5%) from 31 countries, 16.6% had HK (≥5.0 mmol/L) at baseline. Angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) was used in 88.3%, a mineralocorticoid receptor antagonist (MRA) in 58.7%, or a combination in 53.2%; of these, at ≥50% of target dose in ACEi: 61.8%; ARB: 64.7%; and MRA: 90.3%. At a median follow-up of 12.2 months, there were 789 deaths (8.6%). Both hypokalaemia and HK were independently associated with higher mortality, and ACEi/ARB prescription at baseline with lower mortality. MRA prescription was not retained in the model. In multivariable analyses, HK at baseline was independently associated with MRA non-prescription at baseline and subsequent discontinuation. When considering subsequent discontinuation of RAASi (instead of baseline use), HK was no longer found associated with all-cause deaths. Importantly, all RAASi (ACEi, ARB, or MRA) discontinuations were strongly associated with mortality., Conclusions: In HF, hyper- and hypokalaemia were associated with mortality. However, when adjusting for RAASi discontinuation, HK was no longer associated with mortality, suggesting that HK may be a risk marker for RAASi discontinuation rather than a risk factor for worse outcomes., (© 2020 European Society of Cardiology.)

Hyperkalemia in heart failure is a condition that can occur with relative frequency because it is related to pathophysiological aspects of the disease, and favored by drugs that form the basis of chronic cardiac failure therapy. Often, associated comorbidities, such as kidney failure or diabetes mellitus can further adversely affect potassium levels. Hyperkalemia can result in acute and even severe clinical manifestations that put patients at risk. On the other hand, the finding of hyperkalemia in a chronic context can lead to a reduction in dosages or to suspension of drugs such as angiotensin-converting enzymes inhibitor, angiotensin receptor blocker, angiotensin receptor neprilysin inhibitor, and mineralcorticoid receptor antagonist, first line in the treatment of the disease, with negative effects in prognostic terms. Therapies for the correction of hyperkalemia have so far mainly concerned the treatment of acute clinical pictures. Newly developed molecules, such as patiromer or sodium zirconium cyclosilicate, now open new prospectives in the long-term management of hyperkalemia, and allow us to glimpse the possibility of a better titration of the cardinal drugs for heart failure, with consequent positive effects on patient prognosis. The aim of this review is to focus on the problem of hyperkalemia in the setting of heart failure, with particular regard to its incidence, its prognostic role, and the underlining pathophysiological mechanisms. The review also provides an overview of therapeutic strategies for correcting hyperkalemia in acute and chronic conditions, with a focus on the new potassium binders that promise to improve management of heart failure., Competing Interests: The author declares no conflicts of interest., (© 2020 Minà et al. Published by IMR press.)

Renin-angiotensin-aldosterone system inhibitors (RAASi) are recommended for chronic kidney disease (CKD) patients. In this study, we describe RAASi prescription patterns in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, Germany, France, and the United States (US). 5870 patients (mean age 66-72 years; congestive heart failure [CHF] in 11%-19%; diabetes in 43%-54%; serum potassium ≥5 in 20%-35%) were included. RAASi prescription was more common in Germany (80%) and France (77%) than Brazil (66%) and the United States (52%), where the prevalence of prescription decreases particularly in patients with CKD stage 5. In the multivariable regression model, RAASi prescription was least common in the United States and more common in patients who were younger, had diabetes, hypertension, or less advanced CKD. In conclusion, RAASi prescription patterns vary by country, and by demographic and clinical characteristics. RAASi appear to be underused, even among patients with strong class-specific recommendations. Although the reasons for this variation could not be fully identified in this cross-sectional observation, our data indicate that the risk of hyperkalemia may contribute to the underuse of this class of agents in moderate to advanced CKD., (©2019 The Authors. The Journal of Clinical Hypertension Published by Wiley Periodicals, Inc.)

Background: Hyperkalaemia is a significant electrolyte imbalance in chronic kidney disease (CKD). Renin-angiotensin-aldosterone system inhibitors (RAASi) have beneficial cardio-renal properties, although they can often cause hyperkalaemia., Objective: To examine the prevalence of hyperkalaemia in CKD, identify factors associated with its appearance and the relationship between hyperkalaemia and mortality., Patients and Methods: Retrospective observational study on patients with CKD in the period 1971-2017. The population was categorised into 3groups: Group 1, patients with CKD without renal replacement therapy; Group 2, patients on haemodialysis; and Group 3, patients on continuous ambulatory peritoneal dialysis., Results: A total of 2,629 patients were evaluated. The prevalence observed in the different groups was: 9.6%, 16.4% and 10.6%, respectively. Risk factors related to the appearance of hyperkalaemia in the CKD group were glomerular filtration rate (GFR) (P<.001), plasma creatinine (P<.001), plasma sodium (P<.001), haemoglobin (P=.028), diastolic blood pressure (P=.012), intake of ACE inhibitors and/or angiotensin ii receptor blockers (P=.008), treatment with metformin (P<.001) and diabetes (P=.045). Treatment with RAASi significantly increased hyperkalaemia as GFR decreased, as well as in patients with diabetes or heart failure., Conclusions: Hyperkalaemia is a frequent metabolic alteration in CKD patients that increases in the presence of drugs with beneficial cardio-renal properties (RAASi), which means that patients often lose the benefit associated with these drugs. New, recently-appearing non-absorbable compounds, which bind to potassium in the gastrointestinal tract, enhancing faecal excretion and thus maintaining the cardio-renal benefit of the RAASi, could be relevant in the progress of patients with CKD., (Copyright © 2019 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Chronic hyperkalemia (HK) is a serious medical condition that often manifests in patients with chronic kidney disease (CKD) and heart failure (HF) leading to poor outcomes and necessitating careful management by cardionephrologists. CKD, HF, diabetes, and renin-angiotensin-aldosterone system inhibitors use is known to induce HK. Current therapeutic options are not optimal, as pointed out by a large number of CKD and HF patients with HK. The following review will focus on the main risk factors for developing HK and also aims to provide a guide for a correct diagnosis and present new approaches to therapy., (© 2018 S. Karger AG, Basel.)

Hyperkalemia is one of the most common electrolyte disturbances, especially among some groups of patients, such as in those with chronic kidney disease, diabetes or heart failure. Hyperkalemia has been associated with increased risks of mortality, arrhythmias, hospitalization and costs, as well as the need to down titrate/discontinue renin-angiotensin-aldosterone system inhibitors (RAASIs), despite their well-known cardiovascular and nephroprotective benefits. Current potassium binders have limitations (slow onset of action, limited selectivity for potassium binding, risk of drug interactions or gastrointestinal intolerance). Sodium zirconium cyclosilicate (SZC) is a new potassium binder recently approved for the treatment of chronic hyperkalemia. It is a nonabsorbable, inorganic crystal which selectively binds potassium and ammonium in exchange of Na+ and H+ in the whole gastrointestinal tract, achieving a rapid correction of serum potassium levels (within 2 days) and maintaining normokalemia in the long term (up to 1 year), with a good safety profile (common adverse reactions include gastrointestinal events and a dose-dependent risk of edema), excellent tolerability and a low potential for drug interactions. Its potassium-lowering efficacy is maintained irrespective of the use of RAASIs. In summary, SZC is a new potassium binder recently approved for the treatment of hyperkalemia. Its differences with respect to currently available potassium binders make SZC an attractive therapeutic option., (Copyright 2018 Clarivate Analytics.)

Background: Concerns for hyperkalaemia limit the use of mineralocorticoid receptor antagonists (MRAs). The frequency of MRA-associated hyperkalaemia in real-world settings and the extent of subsequent MRA discontinuation are poorly quantified., Methods and Results: Observational study including all Stockholm citizens initiating MRA therapy during 2007-2010. Hyperkalaemias were identified from all potassium (K + ) measurements in healthcare. MRA treatment lengths and dosages were obtained from complete collection of pharmacy dispensations. We assessed the 1-year incidence and clinical hyperkalaemia predictors, and quantified drug prescription changes after an episode of hyperkalaemia. Overall, 13 726 new users of MRA were included, with median age of 73 years, 53% women and median plasma K + of 3.9 mmol/L. Within a year, 18.5% experienced at least one detected hyperkalaemia (K +  > 5.0 mmol/L), the majority within the first 3 monthsnthsnthsnthsnths of therapy. As a comparison, hyperkalaemia was detected in 6.4% of propensity-matched new beta-blocker users. Chronic kidney disease (CKD), older age, male sex, heart failure, peripheral vascular disease, diabetes and concomitant use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers and diuretics were associated with increased hyperkalaemia risk. After hyperkalaemia, 47% discontinued MRA and only 10% reduced the prescribed dose. Discontinuation rates were higher after moderate/severe (K +  > 5.5 mmol/L) and early in therapy (<3 months from initiation) hyperkalaemias. CKD participants carried the highest risk of MRA discontinuation in adjusted analyses. When MRA was discontinued, most patients (76%) were not reintroduced to therapy during the subsequent year., Conclusion: Among real-world adults initiating MRA therapy, hyperkalaemia was very common and frequently followed by therapy interruption, especially among participants with CKD., (© 2018 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Hypo- and hyperkalemia in clinical settings are insufficiently characterized and large-scale data from Europe lacking. We studied incidence and determinants of these abnormalities in a large Swedish healthcare system., Methods: Observational study from the Stockholm CREAtinine Measurements project, including adult individuals from Stockholm accessing healthcare in 2009 (n=364,955). Over 3-years, we estimated the incidence of hypokalemia, defined as potassium<3.5mmol/L, hyperkalemia, defined as potassium>5mmol/L, and moderate/severe hyperkalemia, defined as potassium>5.5mmol/L. Kidney function was assessed by estimated glomerular filtration rate (eGFR)., Results: Of 364,955 participants, 69.4% had 1-2 potassium tests, 16.7% had 3-4 tests and the remaining 13.9% had >4potassiumtests/year. Hypokalemia occurred in 49,662 (13.6%) individuals, with 33% recurrence. Hyperkalemia occurred in 25,461 (7%) individuals, with 35.7% recurrence. Moderate/severe hyperkalemia occurred in 9059 (2.5%) with 28% recurrence. The frequency of potassium testing was an important determinant of dyskalemia risk. The incidence proportion of hyperkalemia was higher in the presence of diabetes, lower eGFR, myocardial infarction, heart failure (HF), or use of renin angiotensin-aldosterone system inhibitors (RAASi). In adjusted analyses, women and use of loop/thiazide diuretics were associated with lower hyperkalemia risk. Older age, lower eGFR, diabetes, HF and use of RAASi were associated with higher hyperkalemia risk. On the other hand, women, younger age, higher eGFR and baseline use of diuretics were associated with higher hypokalemia risk., Conclusion: Hypo- and hyperkalemia are common in healthcare. Optimal RAASi and diuretics use and careful potassium monitoring in the presence of certain comorbidities, especially lower eGFR, is advocated., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: There is increasing awareness of non-adherence to renin-angiotensin- aldosterone system inhibitors (RAASi) in chronic kidney disease (CKD). This study aimed to evaluate the incidence of hyperkalemic adult CKD patients who were prescribed RAASi and to determine variations in pharmacological interventions to uncover reasons for non-adherence to RAASi treatment. Methods: The incidence of hyperkalemia and non-adherence to RAASi [angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blockers (ARBs)] in CKD patients was examined among 471 patients over the age of 18 years who had estimated-glomerular filtration rate (e-GFR) measurements and were diagnosed with CKD between stages 1 and 5. Hyperkalemia was defined as serum potassium (K+) ≥5 mmol/L. The number of hyperkalemic patients not reaching the target dose, hyperkalemia as a reason for not reaching the target dose, patients receiving sodium polystyrene sulfonate patients discontinuing ACEi/ARBs, having a decreased dose of ACEi/ARBs, or treated with the addition or increasing dose of diuretics were compared between the hyperkalemia groups. Results: Hyperkalemia was detected in 29.1% of the patients (n=137), being mild in 21.7%, moderate in 6.2%, and severe in 1.3%. The main finding was that the frequency of patients not reaching the target dose of ACEi/ARBs treatment due to hyperkalemia, hypotension, or e-GFR increase higher than 30% was dramatically higher among patients having moderate/severe hyperkalemia (p

Introduction: There is increasing awareness of non-adherence to renin-angiotensin- aldosterone system inhibitors (RAASi) in chronic kidney disease (CKD). This study aimed to evaluate the incidence of hyperkalemic adult CKD patients who were prescribed RAASi and to determine variations in pharmacological interventions to uncover reasons for non-adherence to RAASi treatment. Methods: The incidence of hyperkalemia and non-adherence to RAASi [angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blockers (ARBs)] in CKD patients was examined among 471 patients over the age of 18 years who had estimated-glomerular filtration rate (e-GFR) measurements and were diagnosed with CKD between stages 1 and 5. Hyperkalemia was defined as serum potassium (K+) ≥5 mmol/L. The number of hyperkalemic patients not reaching the target dose, hyperkalemia as a reason for not reaching the target dose, patients receiving sodium polystyrene sulfonate patients discontinuing ACEi/ARBs, having a decreased dose of ACEi/ARBs, or treated with the addition or increasing dose of diuretics were compared between the hyperkalemia groups. Results: Hyperkalemia was detected in 29.1% of the patients (n=137), being mild in 21.7%, moderate in 6.2%, and severe in 1.3%. The main finding was that the frequency of patients not reaching the target dose of ACEi/ARBs treatment due to hyperkalemia, hypotension, or e-GFR increase higher than 30% was dramatically higher among patients having moderate/severe hyperkalemia (p<0.0001). In 12.41% of hyperkalemic patients, hyperkalemia was cited as the cause for not achieving the target dosage of ACEi/ARB therapy. 25.71% of these patients discontinued ACEi/ARBS treatment, 14.29% had decreased dose of this treatment, and 11.43% had increased dose of diuretics or newly prescribed diuretics. However, none of the patients with mild hyperkalemia experienced these events during treatment. Conclusion: These findings suggest that serum K+ concentration may be related to major adverse clinical outcomes and affect the type of pharmacological intervention in CKD, resulting in ACEi-ARB discontinuation and halting to reach the target dose. [ABSTRACT FROM AUTHOR]

Hyperkalemia is the most common electrolyte imbalance in clinical practice. Hyperkalemia can be caused by an increased intake of potassium into the body, the shift of potassium out of cells or an abnormal renal potassium excretion. This condition is associated with a high risk of death from arrhythmias; therefore, even a slight deviation of the serum potassium level from the norm requires immediate correction. Modern approaches to the treatment of hyperkalemia include the elimination of predictors and the potassium-lowering drugs. Although inhibitors of the renin-angiotensin-aldosterone system are currently the best cardionephroprotective drugs, their administration can lead to hyperkalemia too, especially in heart failure, chronic kidney disease and diabetes mellitus. The article discusses in detail the physiology of potassium metabolism, possible predictors, prevention and treatment of hyperkalemia.

Background: Whether to continue renin–angiotensin–aldosterone system inhibitor (RAASi) therapy in patients with hyperkalemia remains a clinical challenge, particularly in patients with heart failure (HF), where RAASis remain the cornerstone of treatment. We investigated the incidence of dose reduction or the cessation of RAASis and evaluated the threshold of serum potassium at which cessation alters the risk–benefit balance. Methods: This retrospective analysis of a Japanese nationwide claims database investigated treatment patterns of RAASis over 12 months after the initial hyperkalemic episode. The incidences of the clinical outcomes of patients with RAASi (all ACEi/ARB/MRA) or MRA-only cessation (vs. non-cessation) were compared via propensity score-matched patients. A cubic spline regression analysis assessed the hazard of death resulting from treatment cessation vs. no cessation at each potassium level. Results: A total of 5059 hyperkalemic HF patients were identified; most received low to moderate doses of ACEis and ARBs (86.9% and 71.5%, respectively) and low doses of MRAs (76.2%). The RAASi and MRA cessation rates were 34.7% and 52.8% at 1 year post-diagnosis, while the dose reduction rates were 8.4% and 6.5%, respectively. During the mean follow-up of 2.8 years, patients who ceased RAASi or MRA therapies were at higher risk for adverse outcomes; cubic spline analysis found that serum potassium levels of <5.9 and <5.7 mmol/L conferred an increased mortality risk for RAASi and MRA cessation, respectively. Conclusions: Treatment cessation/dose reduction of RAASis are common among HF patients. The risks of RAASi/MRA cessation may outweigh the benefits in patients with mild to moderate hyperkalemia. [ABSTRACT FROM AUTHOR]

Background Hyperkalaemia (HK) is a common electrolyte disorder in patients with chronic kidney disease (CKD) and/or treated with renin–angiotensin–aldosterone system inhibitors (RAASis). The aim of this study is to determine the severity, current management and cost of chronic HK. Methods We performed a retrospective cohort study of patients with chronic HK and CKD, heart failure or diabetes mellitus between 2011 and 2018. The study follow-up was 36 months. Results A total of 1499 patients with chronic HK were analysed: 66.2% presented with mild HK, 23.4% with moderate HK and 10.4% with severe HK. The severity was associated with CKD stage. Most patients (70.4%) were on RAASi therapies, which were frequently discontinued (discontinuation rate was 39.8, 49.8 and 51.8% in mild, moderate and severe HK, respectively). This RAASi discontinuation was similar with or without resin prescription. Overall, ion-exchange resins were prescribed to 42.5% of patients with HK and prescriptions were related to the severity of HK, being 90% for severe HK. Adherence to resin treatment was very low (36.8% in the first year and 17.5% in the third year) and potassium remained elevated in most patients with severe HK. The annual healthcare cost per patient with HK was €5929, reaching €12 705 in severe HK. Costs related to HK represent 31.9% of the annual cost per HK patient and 58.8% of the specialized care cost. Conclusions HK was usually managed by RAASi discontinuation and ion-exchange resin treatment. Most patients with HK were non-adherent to resins and those with severe HK remained with high potassium levels, despite bearing elevated healthcare expenditures. [ABSTRACT FROM AUTHOR]

(1) Background: This observational study aimed to verify the association between serum potassium levels and hospitalization days in patients with chronic kidney disease in a follow up of nine months. (2) Methods: Patients with chronic kidney disease were divided into group A (180 patients, potassium ≤ 5.1 mEq/L) and B (90 patients, potassium > 5.1 mEq/L). Student's t-test, Mann–Whitney test, Pearson's Chi-Square test, Pearson/Spearman's correlation test and linear regression test were performed in the entire sample and in stage-G4/5 subsample. (3) Results: Groups A and B differed for estimated glomerular filtration rate (eGFR) (34.89 (IQR, 16.24–57.98) vs. 19.8 (IQR, 10.50–32.50) mL/min/1.73 m2; p < 0.0001), hemoglobin (11.64 ± 2.20 vs. 10.97 ± 2.19 g/dL, p = 0.048), sum of hospitalization days (8 (IQR, 6–10) vs. 11 (IQR, 7–15) days; p < 0.0001) and use of angiotensin II receptor blockers (40.2% vs. 53.3%; p = 0.010). Considering patients with eGFR 6–30 mL/min/1.73 m2, differences in the sum of hospitalization days were confirmed. Multivariable regression analysis showed that hyperkalemia is an independent risk factor of increased hospital length. In stage G4-G5, regression analysis showed that hyperkalemia is the only independent risk factor (β = 2.93, 95% confidence interval, 0.077–5.794, p = 0.044). (4) Conclusions: We observed significantly greater odds of increased length of hospital stay among patients with higher potassium, mostly in stages G4–G5 chronic kidney disease. [ABSTRACT FROM AUTHOR]