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1.
An evaluation of sodium zirconium cyclosilicate as a treatment option for hyperkalemia.
Takkar, C, Nassar, T, Qunibi, W
Expert opinion on pharmacotherapy. 2021;(1):19-28
Abstract
INTRODUCTION Hyperkalemia, defined as serum potassium level > 5.0 mEq/l, is associated with serious cardiac dysrhythmias, sudden death and increased mortality risk. It is common in patients with chronic kidney disease (CKD), diabetes (DM) and heart failure (HF), particularly in those treated with the renin-angiotensin-aldosterone system (RAAS) inhibitors or potassium-sparing diuretics. Although these drugs have documented renal and cardiac protective benefits, frequent hyperkalemia associated with their use often dictates administration of suboptimal doses or their discontinuation altogether. Treatment for chronic hyperkalemia in these settings has been challenging; however, the recent introduction of two new potassium-binding resins has revolutionized our approach to treating hyperkalemia. AREAS COVERED We review key clinical data relating to the pharmacokinetics, efficacy and safety of sodium zirconium cyclosilicate (SZC) as a treatment option for hyperkalemia. EXPERT OPINION SZC and Patiromer are promising new agents for lowering serum potassium in hyperkalemic patients, including those with CKD, with and without DM or HF, facilitating the use of the RAAS inhibitors for renal and cardiac protection. Recent randomized clinical trials have shown that SZC effectively lowers serum potassium and maintains normokalemia in most hyperkalemic patients. Clinical trials showed that SZC lowers serum potassium within 1 h, although it is not approved for treating acute hyperkalemia. SZC was well tolerated and associated with minimal adverse effects.
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2.
Potassium binding for conservative and preservative management of chronic kidney disease.
Clegg, DJ, Palmer, BF
Current opinion in nephrology and hypertension. 2020;(1):29-38
Abstract
PURPOSE OF REVIEW Hyperkalemia is a life-threatening complication of chronic kidney disease (CKD). Risk factors include advanced kidney impairment, diabetes, hypertension, heart failure, and consumption of a K-enriched diet. High-K diets provide health benefits to include reductions in blood pressure, stroke risk, and osteoporosis. Individuals at the highest risk for developing hyperkalemia are those who would benefit most from high K diets. Inhibitors of the renin--angiotensin--aldosterone system (RAASi) are effective in reducing cardiovascular events and slowing the progression of CKD, yet hyperkalemia is a risk factor. Discussed are new strategies facilitating use of both high-K diets and pharmacology to preserve kidney function and reduce cardiovascular events. RECENT FINDINGS Sodium zirconium cyclosilicate and patiromer are new K-binding drugs approved for the treatment of hyperkalemia. Both are efficacious in the short-term and long-term treatment of hyperkalemia. These binders are effective in treating hyperkalemia while facilitating RAASi therapy. SUMMARY Hyperkalemia is a life-threatening condition. New K-binding drugs allow for optimal use of pharmacological therapy, such as RAASi, enhancing their cardiorenal protection. Health benefits from consumption of high K foods may also be enhanced by use of these binders. In conclusion, there are new well tolerated and effective K-binding agents for acutely and chronically managing hyperkalemia.
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Let Them Eat Healthy: Can Emerging Potassium Binders Help Overcome Dietary Potassium Restrictions in Chronic Kidney Disease?
Sussman, EJ, Singh, B, Clegg, D, Palmer, BF, Kalantar-Zadeh, K
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2020;(6):475-483
Abstract
Potassium-rich foods might provide many health benefits even to people who have declining renal function. The barrier to obtaining these health benefits has long been the concern over hyperkalemia. There are new and novel treatment options available which may enable patients with chronic kidney disease to obtain the health benefits of eating a diet that contains foods such as fruits and vegetables which are high in potassium while reducing the risk of hyperkalemia. We conclude by emphasizing the need for clinical trials with patients on hemodialysis to directly compare the current standard of care, including a potassium-restricted diet, to a potassium-liberalized diet with a potassium binder. The outcome measures would be serum potassium (<5.3 mmol/L), assessments of acidosis, blood pressure, constipation, glycemic control, overhydration, and azotemia, all of which might change in a favorable direction with vegetarian diets as well as quality of life and satisfaction.
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Potassium Binders for Hyperkalemia in Chronic Kidney Disease-Diet, Renin-Angiotensin-Aldosterone System Inhibitor Therapy, and Hemodialysis.
Palmer, BF
Mayo Clinic proceedings. 2020;(2):339-354
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Abstract
Hyperkalemia is a potentially life-threatening complication of chronic kidney disease (CKD). The management of CKD requires balancing the benefits of specific treatments, which may exacerbate the potential for hyperkalemia, with the risks of hyperkalemia itself. Renin-angiotensin-aldosterone system (RAAS) inhibitors, which slow CKD progression and improve cardiovascular outcomes, are often discontinued if hyperkalemia develops. Patients with hyperkalemia are frequently advised to restrict dietary potassium (K+), depriving these patients of many heart-healthy foods. Patients receiving hemodialysis are particularly susceptible to hyperkalemia during long interdialytic intervals, and managing this risk without causing hypokalemia can be challenging. Recently, 2 K+-binding agents were approved for the treatment of hyperkalemia: sodium zirconium cyclosilicate and patiromer. These agents offer alternatives to sodium polystyrene sulfonate, which is associated with serious gastrointestinal adverse effects. For this review, PubMed was searched for English-language articles published in 2014-2018 using the terms patiromer, sodium zirconium cyclosilicate, sodium polystyrene sulfonate, hyperkalemia, renin-angiotensin-aldosterone, diet, and dialysis. In randomized controlled studies of patients with hyperkalemia, sodium zirconium cyclosilicate and patiromer effectively reduced serum K+ and were generally well tolerated. Furthermore, patients in these studies could maintain RAAS inhibitor therapy and, in some studies, were not required to limit dietary K+. There may also be a role for these agents in preventing hyperkalemia in patients receiving hemodialysis. Thus, K+-binding agents may allow patients with CKD at risk for hyperkalemia to optimize RAAS inhibitor therapy, receive benefits of a K+-rich diet, and experience improved hemodialysis outcomes. Additional long-term studies are necessary to confirm these effects.
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Potassium-lowering agents for the treatment of nonemergent hyperkalemia: pharmacology, dosing and comparative efficacy.
Bridgeman, MB, Shah, M, Foote, E
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2019;(Suppl 3):iii45-iii50
Abstract
Hyperkalemia represents a common and potentially life-threating electrolyte abnormality, a complication frequently observed in patients with heart failure, kidney disease, diabetes or in those receiving drug therapies influencing the renin-angiotensin-aldosterone system. Elevated serum potassium levels are often the result of impaired urinary potassium elimination, inadequate or reduced cellular potassium uptake, severe heart failure, use of medications influencing potassium levels in the circulation, or, more commonly, a combination of these factors. Strategies for the treatment of nonemergent hyperkalemia include the use of cation-exchange resins, polymers or other novel mechanisms of potassium trapping, including sodium polystyrene sulfonate, patiromer and sodium zirconium cyclosilicate. These agents differ in their pharmacology and mechanism of action, clinical efficacy, including onset and extent of potassium-lowering effect, dosage and administration, and potential safety and adverse effect profiles. In this review, an evaluation of these characteristics, including clinical evidence and safety concerns, in the management of nonemergent hyperkalemia will be explored.
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[Hyperkalemia in heart failure: new solutions for an old problem].
Romani, S, Porcari, A, Fabris, E, Sinagra, G
Giornale italiano di cardiologia (2006). 2019;(10):543-551
Abstract
Potassium is the main intracellular ion and its homeostasis is finely regulated by the renal and gastrointestinal tract. Renal failure and hyperkalemia are conditions commonly found in patients with heart failure, the result of a complex interaction between heart and kidney (e.g. cardio-renal syndrome) and the side effects of drugs commonly used for treating heart disease (e.g. renin-angiotensin-aldosterone system inhibitors). Although hyperkalemia increases the risk of heart conduction disorders and life-threatening arrhythmias, its prognostic significance in heart failure is uncertain. Hyperkalemia and progression of renal damage are the main limitations to the introduction and titration of heart failure therapies. New drugs for the prevention and chronic treatment of hyperkalemia allow the introduction and modulation of anti-neurohormonal therapies in patients with heart failure otherwise excluded from these treatments due to excessively high serum potassium levels.This review illustrates the pathophysiological, epidemiological and prognostic aspects of hyperkalemia and analyses the possible treatments for this condition in heart failure patients.
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Effect of root canal irrigation protocols on the dislocation resistance of mineral trioxide aggregate-based materials: A systematic review of laboratory studies.
Neelakantan, P, Ahmed, HMA, Wong, MCM, Matinlinna, JP, Cheung, GSP
International endodontic journal. 2018;(8):847-861
Abstract
The aim of this systematic review was to address the question: Do different irrigating protocols have an impact on the dislocation resistance of mineral trioxide aggregate (MTA)-based materials? The review was performed using a well-defined search strategy in three databases (PubMed, Scopus, Web of Science) to include laboratory studies performed between January 1995 and May 2017, in accordance with PRISMA guidelines. Two reviewers analysed the papers, assessed the risk of bias and extracted data on teeth used, sample size, size of root canal preparation, type of MTA-based material, irrigants, canal filling method, storage method and duration, region of roots and the parameters of push-out testing (slice thickness, plunger dimensions and plunger loading direction), the main results and dislocation resistance values (in MPa). From 255 studies, 27 were included for full-text analysis. Eight papers that met the inclusion criteria were included in this review. There was a wide variation in dislocation resistance due to differences in irrigation sequence, time and concentration of irrigants, storage method and duration, and the parameters of push-out bond strength testing. A meta-analysis was not done but qualitative synthesis of the included studies was performed. No definitive conclusion could be drawn to evaluate the effect of irrigation protocols on dislocation resistance of MTA-based materials. Recommendations have been provided for standardized testing methods and reporting of future studies, so as to obtain clinically relevant information and to understand the effects of irrigating protocols on root canal sealers and their interactions with the dentine walls of root canals.
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Boosting the Limited Use of Mineralocorticoid Receptor Antagonists Through New Agents for Hyperkalemia.
Athyros, VG, Sachinidis, AG, Zografou, I, Simoulidou, E, Piperidou, A, Stavropoulos, N, Karagiannis, A
Current pharmaceutical design. 2018;(46):5542-5547
Abstract
BACKGROUND Hyperkalemia is an important clinical problem that is associated with significant lifethreatening complications. Several conditions are associated with increased risk for hyperkalemia such as chronic kidney disease, diabetes mellitus, heart failure, and the use of renin-angiotensin-aldosterone system (RAAS) inhibitors. OBJECTIVE The purpose of this review is to present and critically discuss treatment options for the management of hyperkalemia. METHOD A comprehensive review of the literature was performed to identify studies assessing the drug-induced management of hyperkalemia. RESULTS The management of chronic hyperkalemia seems to be challenging and includes a variety of traditional interventions, such as restriction in the intake of the dietary potassium, loop diuretics or sodium polystyrene sulfonate. In the last few years, several new agents have emerged as promising options to reduce potassium levels in hyperkalemic patients. Patiromer and sodium zirconium cyclosilicate 9 (ZS-9) have been examined in hyperkalemic patients and were found to be efficient and safe. Importantly, the efficacy of these novel drugs might allow the continuation of the use of RAAS inhibitors, morbidity- and mortality-wise beneficial class of drugs in the setting of chronic kidney disease and heart failure. CONCLUSION Data support that the recently emerged patiromer and ZS-9 offer significant hyperkalemia-related benefits. Larger trials are needed to unveil the impact of these drugs in other patients' subpopulations, as well.
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Sodium zirconium cyclosilicate: a new potassium binder for the treatment of hyperkalemia.
Cases, A, Gorriz, JL
Drugs of today (Barcelona, Spain : 1998). 2018;(10):601-613
Abstract
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.
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Gene Expression Profiling and Molecular Signaling of Various Cells in Response to Tricalcium Silicate Cements: A Systematic Review.
Rathinam, E, Rajasekharan, S, Chitturi, RT, Declercq, H, Martens, L, De Coster, P
Journal of endodontics. 2016;(12):1713-1725
Abstract
INTRODUCTION The aim of this study was to present a systematic review investigating the gene expression of various cells (other than dental pulp cells) in response to different variants of tricalcium silicate cements (TSCs). METHODS A systematic search of the literature was performed by 2 independent reviewers followed by article selection and data extraction. Studies analyzing any cell type except dental pulp stem cells and any variant of tricalcium silicate cement either as the experimental or as the control group were included. RESULTS A total of 41 relevant articles were included in this review. Among the included studies, ProRoot MTA (Dentsply, Tulsa, OK) was the most commonly studied (69.1%) TSC variant, and 11 cell types were identified, with 13 articles investigating gene expression in osteoblasts. A total of 39 different genes/molecules expressed were found in the selected studies. The experimental group (irrespective of the TSC variant) was identified to express significantly increased gene expression compared with the control group (untreated) in all included studies. Recent studies have provided useful insight into the gene expression and molecular signaling of various cells in response to TSCs, and new elements have been supplied on the pathways activated in this process. CONCLUSIONS TSCs are capable of eliciting a favorable cellular response in periapical regeneration.