Chronic Hyperkalemia in Cardiorenal Patients: Risk Factors, Diagnosis, and New Treatment Options

Lullo, Luca Di; Ronco, Claudio; Granata, Antonio; Paoletti, Ernesto; Barbera, Vincenzo; Cozzolino, Mario; Ravera, Maura; Fusaro, Maria; Bellasi, Antonio

doi:10.1159/000493395

Cited by 23 publications

(33 citation statements)

References 44 publications

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“…These data suggest that the introduction of new drugs that can better manage hyperkalemia could lead to a more widespread and lasting use of MRA. These new drugs can link the potassium in the gastrointestinal tract, thus reducing its absorption and, as a consequence, its serum levels [15]. They have been shown to be better tolerated than sodium polystyrene sulfonate [15] and, recently, data on the efficacy of their long-term use have been also published [16].…”

Section: Discussionmentioning

confidence: 99%

Mineralcorticoid Receptor Antagonist Withdrawal for Hyperkalemia and Mortality in Patients with Heart Failure

et al. 2020

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Background: Hyperkalemia is one of the most frequent side effects related to renin-angiotensin-aldosterone system (RAAS) inhibition, and can influence optimization of heart failure (HF) therapy. Aim: To evaluate the occurrence of hyperkalemia in a series of outpatients with chronic HF and its relationship with RAAS inhibitor therapy. Method: We evaluated consecutive outpatients with HF and a reduced left ventricular ejection fraction. The incidence of hyperkalemia and consequent changes in RAAS inhibitor therapy were evaluated for each patient. Results: A history of hyperkalemia or at least 1 episode of hyperkalemia during follow-up was observed in 104 of 351 patients. Hyperkalemia mainly influenced mineralocorticoid receptor antagonist (MRA) therapy and, among patients with hyperkalemia, not taking MRA was associated with a greater risk of death on univariate analysis (HR = 6.39; 95% CI 2.76-14.79, p < 0.001) and multivariate analysis (HR = 5.24; 95% CI 1.87-14.72, p = 0.002) after correction for age, ischemic cardiomyopathy, diabetes, systolic arterial pressure, New York Heart Association class 3, left ventricular ejection fraction, presence of hyponatremia, glomerular filtration rate calculated by the EPI formula, and presence of N-terminal pro-B-type natriuretic peptide > 1,000 pg/mL. Conclusion: The occurrence of hyperkalemia is common among outpatients with HF and it is the main cause of MRA withdrawal, which is associated with a worse prognosis. In this setting, the possibility of managing hyperkalemia using new classes of drugs could allow continuation of MRA therapy.

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Section: Discussionmentioning

confidence: 99%

Mineralcorticoid Receptor Antagonist Withdrawal for Hyperkalemia and Mortality in Patients with Heart Failure

et al. 2020

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“…4 These agents have been extensively reviewed. [4][5][6][7][8][9][10] Sodium zirconium cyclosilicate (SZC, formerly ZS-9) is a selective K + -binding agent approved for the treatment of hyperkalaemia in the USA and European Union. 11,12 Because of its specific binding site geometry, SZC selectively binds monovalent cations (particularly excess K + and ammonium) rather than divalent cations such as calcium and magnesium.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of sodium zirconium cyclosilicate for hyperkalaemia: the randomized, placebo‐controlled HARMONIZE‐Global study

et al. 2020

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Aims Sodium zirconium cyclosilicate (SZC, formerly ZS‐9) is a selective K+ binder to treat adults with hyperkalaemia. HARMONIZE‐Global examined the efficacy and safety of SZC among outpatients with hyperkalaemia from diverse geographic and ethnic origins. Methods and results This phase 3, randomized, double‐blind, placebo‐controlled study recruited outpatients with serum K+ ≥5.1 mmol/L (measured by point‐of‐care i‐STAT device) at 45 sites in Japan, Russia, South Korea, and Taiwan. Following open‐label treatment with thrice‐daily SZC 10 g during a 48 h correction phase (CP), patients achieving normokalaemia (K+ 3.5–5.0 mmol/L) were randomized 2:2:1 to once‐daily SZC 5 g, SZC 10 g, or placebo during a 28 day maintenance phase (MP). The primary endpoint was mean central‐laboratory K+ level during days 8–29 of the MP. Of 267 patients in the CP, 248 (92.9%) entered the MP. During the CP, mean central‐laboratory K+ was reduced by 1.28 mmol/L at 48 h vs. baseline (P < 0.001). During the MP (days 8–29), SZC 5 and 10 g once‐daily significantly lowered mean central‐laboratory K+ by 9.6% and 17.7%, respectively, vs. placebo (P < 0.001 for both). More patients had normokalaemia (central‐laboratory K+ 3.5–5.0 mmol/L at day 29) with SZC 5 (58.6%) and 10 g (77.3%) vs. placebo (24.0%), with the greatest number of normokalaemic days in the 10‐g group. The most common adverse events with SZC were mild or moderate constipation and oedema. Conclusions Normokalaemia achieved during the CP was maintained over 28 days with SZC treatment among outpatients with hyperkalaemia.

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“…Current therapeutic options available for managing chronic hyperkalaemia are suboptimal [19] and the introduction of new potassium binding agents provides a new clinical opportunity. In order to implement the effective use of new potassium binders, Imperial College Healthcare NHS Trust have developed a new cross departmental guideline to ensure the optimal use of these agents to maximise the inhibition of RAAS in the patient groups who are likely to bene t from this.…”

Section: Discussionmentioning

confidence: 99%

“…When considering diabetes, hyperkalaemia is probably contributed to by the syndrome of hyporeninaemic hypoaldosteronism, resulting from mild-to-moderate renal impairment [19]. Such patients typically present with asymptomatic hyperkalaemia, commonly occurring in elderly diabetics particularly those on SGLT-2 inhibitor and RAAS inhibitor therapy in the context of impaired renal function [20].…”

Section: Discussionmentioning

confidence: 99%

Analysing the impact of a guideline for the use of new potassium binders for treatment of chronic hyperkalaemia to maximise inhibition of renin–angiotensin–aldosterone system (RAAS) within the general nephrology clinic?

Patel

Frankel

2020

Preprint

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Background Renin–angiotensin–aldosterone system (RAAS) inhibitors provide significant cardiorenal benefits with improved long-term outcomes for patients. This is most significant for patients receiving maximal RAAS inhibition, but some patients are unable to tolerate this therapy because of hyperkalaemia. Recently published National Institute for Health and Care Excellence (NICE) technology appraisal guidance recommended using sodium zirconium cyclosilicate (SZC) and patiromer for patients with chronic kidney disease (CKD) stage 3b to 5 or heart failure with reduced ejection fraction, who are not taking an optimised dosage of RAAS inhibitor because of hyperkalaemia. Objective Determine the impact of a locally produced guideline on effective implementation of NICE recommendation for use of SZC or patiromer to help maximise inhibition of the renin–angiotensin–aldosterone system within the general nephrology clinic. Methods A local guideline to practically support the implementation of recommendations made by NICE in the chronic use of new potassium binders was produced. One hundred sequential patients in a general nephrology clinic with non-immune chronic kidney disease (CKD 3 to 5) had their electronic records reviewed. Those with an indication for RAAS inhibition were identified. Results Of the 100 consecutive patients audited, 46 were female and 54 were male. The mean age of these patients was 64 and the mean estimated glomerular filtration rate (eGFR) was 33. Sixty-eight patients had an indication for being on RAAS inhibition with only 10 on maximal doses. Of the remaining 58 patients, 26 (45%) were limited by hyperkalaemia. Of these 26 patients, 12 of these patients (46%) had hyperkalaemia associated with an episode of acute kidney injury (AKI). Therefore, 14% of patients attending a general nephrology clinic were identified suitable for SZC and patiromer. Conclusions A significant proportion (14%) of unselected patients attending a general nephrology clinic were not on optimum RAAS inhibition due to hyperkalaemia. These patients would meet the criteria established within a working guideline for the implementation of the chronic use of SZC or patiromer and are likely to attain prognostic long-term benefit by using these new potassium binders to maximise RAAS inhibition. This analysis has implications for renal centres across the UK.

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Chronic Hyperkalemia in Cardiorenal Patients: Risk Factors, Diagnosis, and New Treatment Options

Cited by 23 publications

References 44 publications

Mineralcorticoid Receptor Antagonist Withdrawal for Hyperkalemia and Mortality in Patients with Heart Failure

Mineralcorticoid Receptor Antagonist Withdrawal for Hyperkalemia and Mortality in Patients with Heart Failure

Efficacy and safety of sodium zirconium cyclosilicate for hyperkalaemia: the randomized, placebo‐controlled HARMONIZE‐Global study

Analysing the impact of a guideline for the use of new potassium binders for treatment of chronic hyperkalaemia to maximise inhibition of renin–angiotensin–aldosterone system (RAAS) within the general nephrology clinic?

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