Association of Changes in Creatinine and Potassium Levels After Initiation of Renin Angiotensin Aldosterone System Inhibitors With Emergency Department Visits, Hospitalizations, and Mortality in Individuals With Chronic Kidney Disease

Garlo, Katherine; Bates, David W.; Seger, Diane L.; Fiskio, Julie M.; Charytan, David M.

doi:10.1001/jamanetworkopen.2018.3874

Cited by 14 publications

(14 citation statements)

References 33 publications

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“…16 Despite the cardiovascular and renal benefits of optimal RAASi dosing, many patients receive suboptimal dosing or discontinue RAASis, often because of hyperkalaemia. 18,19 In a long-term single-arm open-label study of SZC therapy over 1 year among 746 patients with hyperkalaemia, normokalaemia was maintained for up to 12 months without SZC for hyperkalaemia in HARMONIZE-Global substantial changes in RAASi dosing. 17 Of 483 patients using RAASis at baseline, 87% continued RAASi therapy or the dose was increased, and only 11% discontinued; and of 263 patients not using RAASis at baseline, 14% initiated RAASi therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the cardiovascular and renal benefits of optimal RAASi dosing, many patients receive suboptimal dosing or discontinue RAASis, often because of hyperkalaemia . In a long‐term single‐arm open‐label study of SZC therapy over 1 year among 746 patients with hyperkalaemia, normokalaemia was maintained for up to 12 months without substantial changes in RAASi dosing .…”

Section: Discussionmentioning

confidence: 99%

“…After randomization, serum K + was measured in the morning before the SZC dose on days 1, 2, 5, 8,12,15,19,22,26, and in the morning on day 29 one day after the last dose of SZC on day 28 and at end of study (defined as 7 ± 1 days following last treatment dose). Day 3 of the CP was also considered day 1 of the MP.…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…Despite the benefits of optimal RAASi dosing for slowing cardiovascular and kidney disease progression, many patients received suboptimal dosing or discontinued RAASis, often due to hyperkalaemia [ 21 , 22 ]. Moreover, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are often not able to adequately reduce aldosterone levels, requiring the addition of an MRA [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study

Roger

Lavin

Lerma

et al. 2020

Nephrology Dialysis Transplantation

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Background Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for the treatment of adults with hyperkalaemia. This post hoc analysis of an open-label, single-arm trial (NCT02163499) compared SZC efficacy and safety >12 months among outpatients with hyperkalaemia and Stages 4 and 5 chronic kidney disease (CKD) versus those with Stages 1–3 CKD. Methods Adults with serum K+ ≥5.1 mmol/L (measured by point-of-care i-STAT device) received SZC 10 g three times daily for 24–72 h until normokalaemia (i-STAT K+ 3.5–5.0 mmol/L) was achieved [correction phase (CP)], followed by once daily SZC 5 g for ≤12 months [maintenance phase (MP)]. Here, patients were stratified by baseline estimated glomerular filtration rate (eGFR <30 or ≥30 mL/min/1.73 m2). Study endpoints included percent achieving normokalaemia during CP and MP, mean serum K+ and bicarbonate during MP, and adverse events (AEs). Results Of 751 patients enrolled, 289 (39%), 453 (60%) and 9 (1%) had baseline eGFR values of <30, ≥30 mL/min/1.73 m2 or missing, respectively. During the CP, 82% of patients achieved normokalaemia in both eGFR subgroups within 24 h, and 100 and 95% with baseline eGFR <30 and ≥30 mL/min/1.73 m2, respectively, within 72 h. Corresponding proportions with normokalaemia during the MP were 82 and 90% at Day 365, respectively. Mean serum K+ reduction from baseline during the CP was sustained throughout the MP and serum bicarbonate increased. AEs during the MP were more common in the eGFR <30 ≥30 mL/min/1.73 m2 subgroup. Conclusions SZC corrects hyperkalaemia and maintains normokalaemia among outpatients regardless of the CKD stage.

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“…Notwithstanding the validity of this approach, a prognosticbased definition 203 would convey the graded association with adverse events: risk increases continuously with higher potassium concentrations, and CKD modifies both the distribution of potassium concentration 103 and the associated risk. 169,[204][205][206][207] Incorporating risk factors 103,126,204 into prediction models may help achieve better individual risk stratification. 168,208 There is no consensus on the magnitude, duration, and frequency of elevated potassium values that define chronicity.…”

Section: Chronic Hyperkalemiamentioning

confidence: 99%

Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Clase

Carrero

Ellison

et al. 2020

Kidney International

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303

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Association of Changes in Creatinine and Potassium Levels After Initiation of Renin Angiotensin Aldosterone System Inhibitors With Emergency Department Visits, Hospitalizations, and Mortality in Individuals With Chronic Kidney Disease

Cited by 14 publications

References 33 publications

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

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

Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study

Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

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