Effect of Sodium Zirconium Cyclosilicate on Potassium Lowering for 28 Days Among Outpatients With Hyperkalemia

Kosiborod, Mikhail; Rasmussen, Henrik; Lavin, Philip T.; Qunibi, Wajeh Y.; Spinowitz, Bruce; Packham, David; Roger, Simon D.; Yang, Alex; Lerma, Edgar V.; Singh, Bhupinder

doi:10.1001/jama.2014.15688

Cited by 333 publications

(477 citation statements)

References 35 publications

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“…Although the magnitude of the reduction was relatively small, especially in the sensitivity analyses (80-150 mg), compared with dietary Na intake, patiromer does not add to dietary Na intake in contrast to other K binders in the United States that use Na as a counterexchange ion (2,12,13).…”

Section: Discussionmentioning

confidence: 86%

Effect of Patiromer on Urinary Ion Excretion in Healthy Adults

Bushinsky

Spiegel²,

Gross³

et al. 2016

CJASN

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Background and objectives Patiromer is a nonabsorbed potassium-binding polymer that uses calcium as the counterexchange ion. The calcium released with potassium binding has the potential to be absorbed or bind phosphate. Because binding is not specific for potassium, patiromer can bind other cations. Here, we evaluate the effect of patiromer on urine ion excretion in healthy adults, which reflects gastrointestinal ion absorption.Design, setting, participants, & measurements We analyzed the effect of patiromer on urine potassium, sodium, magnesium, calcium, and phosphate in two studies. Healthy adults on controlled diets in a clinical research unit were given patiromer up to 50.4 g/d divided three times a day for 8 days (dose-finding study) or 25.2 g/d in a crossover design as daily or divided (two or three times a day) doses for 18 days (dosing regimen study). On the basis of 24-hour collections, urinary ion excretion during the baseline period (days 5-11) was compared with that during the treatment period (days 13-19; dose-finding study), and the last 4 days of each period were compared across regimens (dosing regimen study). ResultsIn the dose-finding study, patiromer induced a dose-dependent decrease in urine potassium, urine magnesium, and urine sodium (P,0.01 for each). Patiromer at 25.2 g/d decreased urine potassium (mean6SD) by 11406316 mg/d, urine magnesium by 4561 mg/d, and urine sodium by 2256145 mg/d. Urine calcium increased in a dose-dependent manner, and urine phosphate decreased in parallel (both P,0.01). Patiromer at 25.2 g/d increased urine calcium by 73623 mg/d and decreased urine phosphate by 64640 mg/d. Urine potassium, urine sodium, and urine magnesium were unaffected by dosing regimen, whereas the increase in urine calcium was significantly lower with daily compared with three times a day dosing (P=0.01). Urine phosphate also decreased less with daily compared with two or three times a day dosing (P,0.05).Conclusions In healthy adults, patiromer reduces urine potassium, urine sodium, urine magnesium, and urine phosphate, while modestly increasing urine calcium. Compared with divided dosing, administration of patiromer once daily provides equivalent reductions in urine potassium, urine sodium, and urine magnesium, with less effect on urine calcium and urine phosphate.

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Section: Discussionmentioning

confidence: 86%

Effect of Patiromer on Urinary Ion Excretion in Healthy Adults

Bushinsky

Spiegel²,

Gross³

et al. 2016

CJASN

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“…A total of 258 patients entered the open-label phase, and 237 were randomized into the maintenance phase. 20 The mean baseline serum potassium was 5.6 mEq/L, mean eGFR was 46 mL/min per 1.73 m 2 , and 69% had eGFR <60 mL/min per 1.73 m 2 . CKD was present in 66%, 36% had heart failure, 66% had diabetes mellitus, and 70% were treated with ≥1 RAASi.…”

mentioning

confidence: 88%

“…Serum potassium of <3.5 mEq/L was observed in 10% of patients in the ZS-9 10 g group and 11% of patients in the ZS-9 15 g group versus no cases in the 5 g or placebo groups. 20 No clinically significant changes in serum magnesium, phosphate, or bicarbonate were observed. …”

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confidence: 91%

New Potassium Binders for the Treatment of Hyperkalemia

Pitt

Bakris

2015

Hypertension

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H yperkalemia is a clinical problem with potential mechanisms ranging from increased cellular potassium release (eg, pseudohyperkalemia, metabolic acidosis) to reduced potassium excretion (eg, reduced responsiveness to aldosterone, reduced aldosterone secretion, reduced distal sodium, and water delivery).1,2 Patients with chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) <45 mL/min per 1.73 m 2 , are at increased risk of hyperkalemia, resulting from ≥1 of these mechanisms.3 Renin-angiotensinaldosterone system inhibitors (RAASis) are recommended by guidelines for lowering blood pressure, slowing CKD progression in patients with CKD, 4,5 and reducing cardiovascular mortality and heart failure hospitalizations in patients with heart failure and a reduced ejection fraction, 6,7 but these drugs compound the hyperkalemia risk. 1,[8][9][10] The risk is magnified when the drugs are used in combination (eg, aliskiren in combination with ACE inhibitors or angiotensin receptor blockers; 8,11 mineralocorticoid receptor antagonists in combination with ACE inhibitors or angiotensin receptor blockers). Moreover, the risk for hyperkalemia is magnified in diseases, such as diabetes mellitus and heart failure. 4,5,12,13 The occurrence or fear of inducing hyperkalemia has led to premature discontinuation, suboptimal dosing, and often failure to use an RAASi, thereby exposing patients to increased cardiovascular risk.Current treatment approaches for chronic hyperkalemia are limited. Options for the management of hyperkalemia include discontinuation or reduced doses of RAASi, administration of loop diuretics, dietary potassium restriction, or sodium polystyrene sulfonate.14 None of these approaches are optimal because they require withholding life-saving or kidney preserving therapy (ie, RAASi), have a low rate of patient adherence (eg, dietary restriction), or have an unfavorable adverse effect profile and low tolerability (ie, sodium polystyrene sulfonate). 15 New agents to treat hyperkalemia are in the late stages of development. Clinical trial data suggest that these new agents effectively lower serum potassium and are well tolerated. [16][17][18][19][20] Therefore, these agents offer promising advantages over existing management options. It is possible that these agents might also facilitate maintenance of RAASi across the broad spectrum of patients with RAASi intolerance because of hyperkalemia (eg, CKD and heart failure), 18 and testing this hypothesis in larger clinical trials is warranted. This article reviews the clinical problem of hyperkalemia and identifies predictors of hyperkalemia in patients with hypertension, CKD, diabetes mellitus, and heart failure. It also presents recent clinical trial evidence of the efficacy and safety of new treatments for hyperkalemia, and it discusses how these agents may be used clinically, if approved. Overview of HyperkalemiaThe rate of hyperkalemia is low in uncomplicated hypertension patients treated with RAASi, 21 but it rises in the setting o...

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“…In short, ZS-9 is an orally administered and sorbitol-free potassium trap, which binds potassium (in exchange for sodium) in a highly selective way in the gastrointestinal tract (mainly duodenum) [109]. Three randomized, placebo-controlled phase-2 and -3 trials focused on the effectivity and safety of ZS-9 in a broad range of hyperkalemic subjects [110][111][112]. All trials demonstrated a significant potassium level reduction in the ZS-9 groups compared to placebo, both in the initiation and maintenance phase.…”

Section: Sodium Zirconium Cyclosilicate (Zs-9)mentioning

confidence: 99%

Pharmacotherapy for comorbidities in chronic heart failure: a focus on hematinic deficiencies, diabetes mellitus and hyperkalemia

Wal

Beverborg

Veldhuisen³

et al. 2016

Expert Opinion on Pharmacotherapy

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Introduction: Chronic heart failure (HF) is frequently accompanied by one or more comorbidities. The presence of comorbidities in chronic HF is strongly correlated to HF severity and impaired outcome. Areas covered: This review will address several comorbidities with high prevalence and/or high impact in patients with chronic HF, including diabetes, anemia, hematinic deficiencies, and hyperkalemia. The background and subsequent pharmacotherapeutic options of these comorbidities will be discussed. For this review, a MEDLINE search was performed. Expert opinion: Heart failure is increasingly considered a multimorbid syndrome, including metabolic derangements and chronic inflammation. Persistent metabolic derangements and low-grade inflammation might lead to progression of HF and the development of comorbidities. Although several comorbidity-specific drugs became available in the past decade, most of these therapies are studied in relatively small cohorts using surrogate end-points. Therefore, larger studies are needed to address whether treating these comorbidities will improve patient outcome in chronic HF. ARTICLE HISTORY

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Effect of Sodium Zirconium Cyclosilicate on Potassium Lowering for 28 Days Among Outpatients With Hyperkalemia

Abstract: clinicaltrials.gov Identifier: NCT02088073.

Cited by 333 publications

References 35 publications

Effect of Patiromer on Urinary Ion Excretion in Healthy Adults

Effect of Patiromer on Urinary Ion Excretion in Healthy Adults

New Potassium Binders for the Treatment of Hyperkalemia

Pharmacotherapy for comorbidities in chronic heart failure: a focus on hematinic deficiencies, diabetes mellitus and hyperkalemia

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