Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial
Abstract
Importance Hyperkalemia is a potentially life-threatening condition predominantly seen in patients treated with renin-angiotensin-aldosterone system (RAAS) inhibitors with stage 3 or greater chronic kidney disease (CKD) who may also have diabetes, heart failure, or both. Objectives To select starting doses for a phase 3 study and to evaluate the long-term safety and efficacy of a potassium-binding polymer, patiromer, in outpatients with hyperkalemia. Design, setting, and participants Phase 2, multicenter, open-label, dose-ranging, randomized clinical trial (AMETHYST-DN), conducted at 48 sites in Europe from June 2011 to June 2013 evaluating patiromer in 306 outpatients with type 2 diabetes (estimated glomerular filtration rate, 15 to 5.0 mEq/L). All patients received RAAS inhibitors prior to and during study treatment. Interventions Patients were stratified by baseline serum potassium level into mild or moderate hyperkalemia groups and received 1 of 3 randomized starting doses of patiromer (4.2 g [n = 74], 8.4 g [n = 74], or 12.6 g [n = 74] twice daily [mild hyperkalemia] or 8.4 g [n = 26], 12.6 g [n = 28], or 16.8 g [n = 30] twice daily [moderate hyperkalemia]). Patiromer was titrated to achieve and maintain serum potassium level 5.0 mEq/L or lower. Main outcomes and measures The primary efficacy end point was mean change in serum potassium level from baseline to week 4 or prior to initiation of dose titration. The primary safety end point was adverse events through 52 weeks…
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Efficacy and safety data beyond 1 year of treatment with potassium binders are not available.
“ef fi cacy and safety data beyond 1 year of treatment are not available;”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [83]
Clinical outcomes were not evaluated in the studies of potassium binders.
“However, clinical outcomes were not evaluated;”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [83]
Both studies demonstrated the effectiveness of achieving normokalemia and that treatment with RAS blockade agents can be continued without treatment-related serious adverse effects.
“Both studies demonstrated the effectiveness of achieving normokalemia and that treatment with RAS blockade agents can be continued without treatment-related serious adverse effects.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [83]
Treatment with potassium binders, such as patiromer or sodium zirconium cyclosilicate, has been used to treat hyperkalemia associated with RAS blockade therapy for up to 12 months.
“Treatment with potassium binders, such as patiromer or sodium zirconium cyclosilicate, where each has been used to treat hyperkalemia associated with RAS blockade therapy for up to 12 months. 83,84”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [83]
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Self-citation
- Authors
- Bakris, G. L., Pitt, B., Weir, M. R., Freeman, M. W., Mayo, M. R., Garza, D., Stasiv, Y., Zawadzki, R., Berman, L., & Bushinsky, D. A.
- Affiliations
- University of Chicago (US)
- University of Michigan (US)
- University of Maryland, Baltimore (US)
- Massachusetts General Hospital (US)
- Relypsa (United States) (US)
- University of Rochester Medicine (US)
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2015-07-14
- Volume
- 314
- Issue
- 2
- Pages
- 151
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W1756552807
- Cited by
- 441
- References
- 6
- Citations by year
- 2026: 21 · 2025: 15 · 2024: 39 · 2023: 42 · 2022: 43 · 2021: 48 · 2020: 35 · 2019: 43 · 2018: 45 · 2017: 43 · 2016: 49 · 2015: 17
- FWCI
- 40.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Potassium and Related Disorders
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- patiromer, hyperkalemia, serum potassium, diabetic nephropathy, type 2 diabetes, renin-angiotensin-aldosterone system inhibitors, chronic kidney disease, dose titration, adverse events, drug safety, drug efficacy, outpatients, heart failure, heart failure with reduced ejection fraction, heart failure with preserved ejection fraction
- MeSH terms
- Administration, Oral, Adult, Aged, Angiotensin-Converting Enzyme Inhibitors, Diabetic Nephropathies, Female, Humans, Hyperkalemia, Male, Middle Aged, Polymers, Potassium, Renin-Angiotensin System, Least-Squares Analysis
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