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Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial

Published on Jul 14, 2015in JAMA51.27
· DOI :10.1001/jama.2015.7446
George L. Bakris102
Estimated H-index: 102
(U of C: University of Chicago),
Bertram Pitt99
Estimated H-index: 99
(UM: University of Michigan)
+ 7 AuthorsDavid A. Bushinsky53
Estimated H-index: 53
(UR: University of Rochester)
Cite
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 2 and serum potassium level >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. Secondary efficacy end points included mean change in serum potassium level through 52 weeks. Results A total of 306 patients were randomized. The least squares mean reduction from baseline in serum potassium level at week 4 or time of first dose titration in patients with mild hyperkalemia was 0.35 (95% CI, 0.22-0.48) mEq/L for the 4.2 g twice daily starting-dose group, 0.51 (95% CI, 0.38-0.64) mEq/L for the 8.4 g twice daily starting-dose group, and 0.55 (95% CI, 0.42-0.68) mEq/L for the 12.6 g twice daily starting-dose group. In those with moderate hyperkalemia, the reduction was 0.87 (95% CI, 0.60-1.14) mEq/L for the 8.4 g twice daily starting-dose group, 0.97 (95% CI, 0.70-1.23) mEq/L for the 12.6 g twice daily starting-dose group, and 0.92 (95% CI, 0.67-1.17) mEq/L for the 16.8 g twice daily starting-dose group ( P Conclusions and Relevance Among patients with hyperkalemia and diabetic kidney disease, patiromer starting doses of 4.2 to 16.8 g twice daily resulted in statistically significant decreases in serum potassium level after 4 weeks of treatment, lasting through 52 weeks. Trial Registration clinicaltrials.gov Identifier:NCT01371747
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  • References (36)
  • Citations (148)
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References36
Newest
Published on Jan 15, 2015in The New England Journal of Medicine70.67
Matthew R. Weir66
Estimated H-index: 66
(UMB: University of Maryland, Baltimore),
George L. Bakris102
Estimated H-index: 102
(U of C: University of Chicago)
+ 7 AuthorsBertram Pitt99
Estimated H-index: 99
(UM: University of Michigan)
Background Hyperkalemia increases the risk of death and limits the use of inhibitors of the renin–angiotensin–aldosterone system (RAAS) in high-risk patients. We assessed the safety and efficacy of patiromer, a nonabsorbed potassium binder, in a multicenter, prospective trial. Methods Patients with chronic kidney disease who were receiving RAAS inhibitors and who had serum potassium levels of 5.1 to less than 6.5 mmol per liter received patiromer (at an initial dose of 4.2 g or 8.4 g twice a day...
Published on Jan 1, 2014in Circulation-heart Failure6.53
Patrick Rossignol40
Estimated H-index: 40
(University of Lorraine),
Daniela Dobre13
Estimated H-index: 13
(University of Lorraine)
+ 10 AuthorsNicolas Girerd18
Estimated H-index: 18
(University of Lorraine)
Background—Mineralocorticoid receptor antagonists improve outcomes in patients with systolic heart failure but may induce worsening of renal function (WRF) and hyperkalemia (HK). We assessed the risk factors for mineralocorticoid receptor antagonist–related WRF and for HK, as well as the association between HK and WRF with clinical outcomes in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Methods and Results—Serial changes in estimated glomeru...
Published on Jan 1, 2014in Journal of Clinical Hypertension2.44
Michael Weber71
Estimated H-index: 71
,
Ernesto L. Schiffrin99
Estimated H-index: 99
+ 22 AuthorsC. Venkata S. Ram18
Estimated H-index: 18
Clinical practice guidelines for the management of hypertension in the community a statement by the American society of hypertension and the International society of hypertension
Published on Jan 1, 2014
Lee A. Fleisher74
Estimated H-index: 74
,
Kirsten E. Fleischmann34
Estimated H-index: 34
+ 14 AuthorsCrystal C. Spencer4
Estimated H-index: 4
Published on Oct 15, 2013in Journal of the American College of Cardiology18.64
Clyde W. Yancy93
Estimated H-index: 93
,
Mariell Jessup64
Estimated H-index: 64
+ 21 AuthorsJames L. Januzzi75
Estimated H-index: 75
Jeffrey L. Anderson, MD, FACC, FAHA, Chair; Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair[‡‡][1]; Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect; Nancy M. Albert, PhD, CCNS, CCRN, FAHA; Biykem Bozkurt, MD, PhD, FACC, FAHA; Ralph G. Brindis, MD, MPH, MACC; Mark A. Creager, MD, FACC,
Published on Sep 1, 2013in Circulation-heart Failure6.53
Orly Vardeny15
Estimated H-index: 15
(UW: University of Wisconsin-Madison),
Larisa H. Cavallari25
Estimated H-index: 25
(UIC: University of Illinois at Chicago)
+ 6 AuthorsScott D. Solomon104
Estimated H-index: 104
(Brigham and Women's Hospital)
Background—The incidence of hyperkalemia caused by mineralocorticoid receptor antagonists may vary by race, but whether race influences efficacy of mineralocorticoid receptor antagonists in heart failure (HF) is unknown. Methods and Results—We assessed hyperkalemia and outcomes in African Americans (AAs; n=120) and non-AAs (n=1543; white 93%) with New York Heart Association (NYHA) class III or IV HF and left ventricular dysfunction who were randomized to spironolactone, titrated to 25 or 50 mg d...
Published on Mar 1, 2013in The American Journal of Medicine4.76
Ziv Harel17
Estimated H-index: 17
(St. Michael's Hospital),
Shai Harel7
Estimated H-index: 7
(St. Michael's Hospital)
+ 3 AuthorsChaim M. Bell49
Estimated H-index: 49
(U of T: University of Toronto)
Abstract Background Sodium polystyrene sulfonate (Kayexalate; Sanofi-Aventis, Paris, France) is a cation-exchange resin routinely used in the management of hyperkalemia. However, its use has been associated with colonic necrosis and other fatal gastrointestinal adverse events. Although the addition of sorbitol to sodium polystyrene sulfonate preparations was previously believed to be the cause of gastrointestinal injury, recent reports have suggested that sodium polystyrene sulfonate itself may ...
Published on Mar 1, 2013in The American Journal of Medicine4.76
Jiing-ChyuanLuo25
Estimated H-index: 25
(NYMU: National Yang-Ming University),
Hsin-Bang Leu27
Estimated H-index: 27
(NYMU: National Yang-Ming University)
+ 6 AuthorsJaw-Wen Chen45
Estimated H-index: 45
Abstract Objectives Hemodialysis patients carry a higher risk of peptic ulcer bleeding. Whether hemodialysis patients also have a higher occurrence of nonpeptic ulcer, nonvariceal gastrointestinal bleeding needs further evaluation. Methods Using Taiwan's National Health Insurance research database, the occurrence of nonpeptic ulcer, nonvariceal gastrointestinal bleeding was compared among the hemodialysis patients, chronic kidney disease patients, and controls using log-rank test. Risk factors w...
Published on Feb 1, 2013in Diabetes Care15.27
Silvio E. Inzucchi71
Estimated H-index: 71
,
Richard M. Bergenstal57
Estimated H-index: 57
+ 7 AuthorsMatthews1
Estimated H-index: 1
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycemia in type 2 …
Published on Jan 1, 2013in Kidney International8.31
Adeera Levin64
Estimated H-index: 64
(UBC: University of British Columbia),
Pe Stevens1
Estimated H-index: 1
(National Health Service)
+ 13 AuthorsEj Lamb1
Estimated H-index: 1
(UBC: University of British Columbia)
Cited By148
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Published on Dec 1, 2019in Biomedical Engineering Online2.01
Alexander F. Smith (UMass: University of Massachusetts Amherst), Bin Zhao2
Estimated H-index: 2
(UMass: University of Massachusetts Amherst)
+ 1 AuthorsJuan M. Jiménez (UMass: University of Massachusetts Amherst)
Background Patients with end-stage renal disease (ESRD) have failed kidney function, and often must be treated with hemodialysis to extend the patient’s life by artificially removing excess fluid and toxins from the blood. However, life-threatening treatment complications can occur because hemodialysis protocols are adjusted infrequently, as opposed to the kidneys which filter blood continuously. Infrequent blood tests, about once per month on average, are used to adjust hemodialysis protocols a...
Published on Feb 28, 2019in Annals of Intensive Care3.93
François Dépret3
Estimated H-index: 3
(French Institute of Health and Medical Research),
W. Frank Peacock34
Estimated H-index: 34
(BCM: Baylor College of Medicine)
+ 3 AuthorsMatthieu Legrand24
Estimated H-index: 24
To review the mechanisms of action, expected efficacy and side effects of strategies to control hyperkalemia in acutely ill patients. We searched MEDLINE and EMBASE for relevant papers published in English between Jan 1, 1938, and July 1, 2018, in accordance with the PRISMA Statement using the following terms: “hyperkalemia,” “intensive care,” “acute kidney injury,” “acute kidney failure,” “hyperkalemia treatment,” “renal replacement therapy,” “dialysis,” “sodium bicarbonate,” “emergency,” “acut...
Published on Sep 1, 2019in The Lancet59.10
Rajiv Agarwal62
Estimated H-index: 62
(IU: Indiana University),
Patrick Rossignol40
Estimated H-index: 40
(French Institute of Health and Medical Research)
+ 6 AuthorsBryan Williams63
Estimated H-index: 63
(NIHR: National Institute for Health Research)
Summary Background Spironolactone is effective at reducing blood pressure in patients with uncontrolled resistant hypertension. However, the use of spironolactone in patients with chronic kidney disease can be restricted by hyperkalaemia. We evaluated use of the potassium binder patiromer to allow more persistent use of spironolactone in patients with chronic kidney disease and resistant hypertension. Methods In this phase 2 multicentre, randomised, double-blind, placebo-controlled study, we enr...
Published on Apr 8, 2019in Pediatric Nephrology2.82
Neil J. Paloian2
Estimated H-index: 2
(UW: University of Wisconsin-Madison),
Barbara Bowman (UW: University of Wisconsin-Madison), Sharon M. Bartosh17
Estimated H-index: 17
(UW: University of Wisconsin-Madison)
Background Hyperkalemia is a potentially life-threatening complication of chronic kidney disease (CKD). Dietary potassium restriction is challenging in infants despite low-potassium formulas. Decreasing potassium in formula using patiromer, a new calcium-based cation exchange polymer may be one option to accomplish this; however, data confirming efficacy is lacking.
Published on May 22, 2019in Journal of Nephrology3.70
Stefano Bianchi22
Estimated H-index: 22
,
Filippo Aucella20
Estimated H-index: 20
+ 3 AuthorsGiuseppe Regolisti20
Estimated H-index: 20
Hyperkalemia (HK) is the most common electrolyte disturbance observed in patients with kidney disease, particularly in those in whom diabetes and heart failure are present or are on treatment with renin–angiotensin–aldosterone system inhibitors (RAASIs). HK is recognised as a major risk of potentially life threatening cardiac arrhythmic complications. When an acute reduction of renal function manifests, both in patients with chronic kidney disease (CKD) and in those with previously normal renal ...
Published on Sep 19, 2018in Internal Medicine Journal1.77
Ria Arnold9
Estimated H-index: 9
(UNSW: University of New South Wales),
Timothy J. Pianta9
Estimated H-index: 9
(University of Melbourne)
+ 3 AuthorsArun V. Krishnan29
Estimated H-index: 29
(UNSW: University of New South Wales)
Published on Jun 1, 2019in Current Heart Failure Reports
Mengyang Liu (BCM: Baylor College of Medicine), Zubaid Rafique5
Estimated H-index: 5
(BCM: Baylor College of Medicine)
Purpose of the Review Hyperkalemia is a common electrolyte abnormality that can lead to life-threatening cardiac arrhythmia. Medical management of acute hyperkalemia revolves around three strategies—stabilizing the myocardium, intracellular shifting of serum potassium, and enhancing elimination of total body potassium via urinary or fecal excretion. In this review, we outline the current evidence behind the acute medical management of hyperkalemia.
Published on Apr 1, 2019in Esc Heart Failure
Cecilia Linde51
Estimated H-index: 51
(Karolinska University Hospital),
Lei Qin2
Estimated H-index: 2
(AstraZeneca)
+ 6 AuthorsPhil McEwan21
Estimated H-index: 21
(Swansea University)
Published on Mar 1, 2019in Heart Failure Reviews4.01
David Goldgrab1
Estimated H-index: 1
(University of Connecticut Health Center),
Kathir Balakumaran1
Estimated H-index: 1
(University of Connecticut Health Center)
+ 1 AuthorsSara Tabtabai2
Estimated H-index: 2
(University of Connecticut Health Center)
Heart failure (HF) and HF 30-day readmission rates have been a major focus of efforts to reduce health care cost in the recent era. Since the implementation of the Affordable Care Act (ACA) in 2012 and the Hospital Readmission Reduction Program (HRRP), concerted efforts have focused on reduction of 30-day HF readmissions and other admission diagnoses targeted by the HRRP. Hospitals and organizations have instituted wide-ranging programs to reduce short-term readmissions, but the data supporting ...
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