A to Z Health Guide

Clinical Highlights: Hyerkalemia in CKD Patients

A brief collection of recent and/or notable journal articles about hyperkalemia in patients with chronic kidney disease (CKD) can be accessed here. 


Epidemiology of hyperkalemia: an update

By Kovesdy, C.P.
Kidney Inter, 2016. 6: p. 3-6.
Hyperkalemia is relatively rare in patients with normal kidney function but much more common among patients with CKD, especially in those exposed to exacerbating factors.  Of the factors causing hyperkalemia, lower GFR and treatment with RAASis are perhaps the most significant. Read More


Association between serum potassium and outcomes in patients with reduced kidney function

By Luo, J., et al.
Clin J Am Soc Nephrol, 2016. 11(1): p. 90-100.
The association of serum postassium (K+) with mortality and hospitalization rates among 55,266 CKD patients with serum K+ data were studied between 2009 to 2013 in order to understand how the burden of hyperkalemia varies by CKD severity.  Mortality, major adverse cardiovascular events, hospitalization, and discontinuation of RAAS blockers were considered. Read More

Serum potassium and cause-specific mortality in a large peritoneal dialysis cohort

By Torlen, K., et al.
Clin J Am Soc Nephrol, 2012. 7(8): p. 1272-84.
Data from patients treated in DaVita facilities between July 1, 2001 and June 30, 2006 (n=10,468 PD patients; n=111,651 HD patients) were used to determine association of serum potassium with mortality.  Read More

Serum potassium and short-term clinical outcomes among hemodialysis patients: impact of the long interdialytic interval

By Brunelli, S.M., et al.
Am J Kidney Dis, 2017. DOI: 10.1053/j.ajkd.2016.10.024. [Epub ahead of print]
The interplay among serum potassium, dialysis cycle phase, and clinical outcomes is examined in a retrospective observational study of 52,734 patients receiving in-center hemodialysis at a large dialysis organization during 2010 and 2011. Read More


Current and future treatment options for managing hyperkalemia

By Weir, M.R.
Kidney Inter Supp., 2016. 6: p. 29-34.
Hyperkalemia remains a vexing problem for clinicians, particularly in the care of patients with chronic kidney disease and cardiovascular disease. Read More

Emergency management of severe hyperkalemia: Guideline for best practice and opportunities for the future

By Rossignol, P., et al.
Pharmacol Res, 2016. 113(Pt A): p. 585-591.
Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT) aimed to evaluate the current knowledge pertaining to the emergency treatment of hyperkalemia. The INI-CRCT developed a treatment algorithm reflecting expert opinion of best practices in the context of current evidence, identified gaps in knowledge, and set priorities for future research. Read More

Management of hyperkalaemia in chronic kidney disease

By Kovesdy, C.P.
Nat Rev Nephrol, 2014. 10(11): p. 653-62.
Hyperkalaemia is common in patients with chronic kidney disease (CKD), in part because of the effects of kidney dysfunction on potassium homeostasis and in part because of the cluster of comorbidities (and their associated treatments) that occur in patients with CKD. The emergence of new medications that specifically target hyperkalaemia could lead to a therapeutic paradigm shift.  Read More

Treatment of hyperkalemia: something old, something new

By Sterns, R.H., M. Grieff, and P.L. Bernstein
Kidney Inter, 2016. 89(3): p. 546-54.
Although there are some concerns about hypomagnesemia and positive calcium balance from patiromer, and sodium overload from sodium polystyrene sulfonate (ZS-9) , both agents have been shown to be effective and well tolerated when taken chronically.  Read More

Updates in hyperkalemia: Outcomes and therapeutic strategies

By Kovesdy,  C.P.
Rev Endocr Metab Disord., 2016. Sep 6. doi:10.1007/s11154-016-9384-x
This review article examines the incidence and clinical consequences of hyperkalemia, and its various treatment options, with special emphasis on novel therapeutic agents and the potential benefits of their application. Read More

New Potassium-Binding Agents (Reviews & Meta-Analysis)

Advances in the management of hyperkalemia in chronic kidney disease

By Cowan, A.C., E.G. Gharib, and M.A. Weir
Curr Opin Nephrol Hypertens, 2017.  doi: 10.1097/MNH.0000000000000320. [Epub ahead of print]
Patients with chronic kidney disease (CKD) have an increased risk of hyperkalemia that increases both short-term and long-term mortality. This review discusses current treatments and their limitations and summarizes the evidence supporting novel agents for potassium lowering in patients with CKD. Read More

Potassium-binding agents for the clinical management of hyperkalemia

By Chaitman, M., D. Dixit, and M.B. Bridgeman
P & T, 2016. 41(1): p. 43-50.
Sodium zirconium cyclosilicate (ZS-9) and patiromer are expected to offer greater binding selectivity for potassium compared with that of sodium polystyrene sulfonate (SPS). Read More

Potassium-binding agents to facilitate renin-angiotensin-aldosterone system inhibitor therapy

By Schaefer, J.A. and M.A. Gales
Ann Pharmacother., 2016. 50(6): p. 502-10.
The literature does not currently support sodium polystyrene sulfonate (SPS) and calcium polystyrene sulfonate (CLP) for preventing RAAS inhibitor-associated hyperkalemia. Patiromer and sodium polystyrene sulfonate (ZS-9) safely and effectively lower serum potassium and prevent hyperkalemia redevelopment in patients receiving RAAS inhibitors for up to 4 and 8 weeks.  Read More

Potential new agents for the management of hyperkalemia

By Packham, D.K. and M. Kosiborod
Am J Cardiovas Drugs , 2016. 16(1): p. 19-31.
This review discusses the merits of patiromer and sodium zirconium cyclosilicate (ZS-9) and how they may help optimize the future management of patients with hyperkalemia.  Patiromer sorbitex calcium is a polymer resin and sorbitol complex that binds potassium in exchange for calcium; ZS-9 is a non-absorbed, highly selective inorganic cation exchanger that traps potassium in exchange for sodium and hydrogen. Read More

Systematic review and meta-analysis of patiromer and sodium zirconium cyclosilicate: A new armamentarium for the treatment of hyperkalemia

By Meaney, C.J., et al.
Pharmacotherapy, 2017.
A systematic review and meta-analysis of phase II and III clinical trial data was completed in order to compare the efficacy and safety of patiromer and sodium zirconium cyclosilicate (ZS-9) in the treatment of hyperkalemia.  The authors concluded that patiromer and ZS-9 represent significant pharmacologic advancements in the treatment of hyperkalemia. Both agents exhibited statistically and clinically significant reductions in potassium for the primary endpoint of this meta-analysis.  Read More

Pivotal Clinical Studies

Sodium Zirconium Cyclosilicate (ZS-9)

A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient

By Ash, S.R., et al.
Kidney Int., 2015. 88(2): p. 404-11
The results of a phase 2, randomized, double-blind, placebo-controlled dose-escalation study to assess safety and efficacy of sodium polystyrene sulfonate (ZS-9) are presented. Read More

Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial

By Kosiborod, M., et al.
JAMA, 2014. 312(21): p. 2223-33.
HARMONIZE was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating zirconium cyclosilicate in outpatients with hyperkalemia recruited from 44 sites in the United States, Australia, and South Africa (March-August 2014). Read More

Sodium zirconium cyclosilicate in hyperkalemia

By Packham, D.K., et al.
N Engl J Med, 2015. 372(3): p. 222-31.
The results of a multicenter, two-stage, double-blind, phase 3 trial, in which 753 patients with hyperkalemia were randomized to receive either sodium polystyrene sulfonate (ZS-9)  or placebo three times daily for 48 hours are presented. Patients with normokalemia at 48 hours were randomly assigned to receive either ZS-9 or placebo once daily on days 3 to 14 (maintenance phase). The primary end point was the exponential rate of change in the mean serum potassium level at 48 hours.  Read More

Sodium zirconium cyclosilicate for urgent therapy of severe hyperkalemia

N Engl J Med, 2015; p 372:1577-1578
By Kosiborod, M., W. F. Peacock, and D. K. Packham
This letter to the editor, published in the New England Journal of Medicine, reports the short-term changes in the serum potassium level within the first 4 hours after an initial 10-g dose of sodium polystyrene sulfonate (ZS-9) in a subgroup of patients with severe hyperkalemia.  Read More


Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: The AMETHYST-DN randomized clinical trial

By Bakris, G.L., et al.
JAMA, 2015. 314(2): p. 151-61.
A phase 2, multicenter, open-label, dose-ranging, randomized clinical trial (AMETHYST-DN), conducted at 48 sites in Europe from June 2011 to June 2013, evaluated patiromer in 306 outpatients with type 2 diabetes (eGFR, 15 to <60  and serum potassium level >5.0 mEq/L). All patients received RAAS inhibitors prior to and during study treatment.  Read More

Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial

By Pitt, B., et al.
Eur Heart J,  2011. 32(7): p. 820-8.
A phase 2b, randomized, placebo-controlled, double-blind trial (PEARL-HF) was conducted to evaluate the safety and efficacy of patiromer in 104 heart failure patients who had CKD or a documented history of hyperkalemia which had led to discontinuation of therapy (RAASi or beta-blocker).  Read More

Patiromer induces rapid and sustained potassium lowering in patients with chronic kidney disease and hyperkalemia

By Bushinsky, D.A, et al.
A phase 1, open-label study of 25 CKD patients with sustained hyperkalemia on a sodium- and potassium-restricted diet taking at least one RAASi was conducted to determine whether patiromer can induce an early and sustained reduction in serum potassium from baseline during 48H.  Read More

Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors

By Weir, M.R., et al.
N Engl J Med., 2015. 372(3): p. 211-21.
A phase 3, randomized, placebo-controlled trial (OPAL-HK) was conducted to evaluate the safety and efficacy of patiromer in 237 hyperkalemic patients with CKD receiving RAAS inhibitor therapy.  Read More

Sodium Polystyrene Sulfonate (SPS)

Asking the question again: Are cation exchange resins effective for the treatment of hyperkalemia?

Nephrol Dial Transplant. 2012. 27(12): p. 4294-7.
By Kamel , S. K., and M. Schreiber
In this editorial, the authors ask whether cation exchange resins are effective in treatment of hyperkalemia.  Their analysis is based on considerations of the binding characteristics of sodium polystyrene sulfonate (SPS), the concentration of electrolytes in the lumen of different segments of the GI tract, what is required to achieve a high rate of excretion of K+ in stool, and on examining the available evidence in the literature. Read More

Ion-Exchange Resins for the Treatment of Hyperkalemia: Are They Safe and Effective?

By Sterns, R.H., M. Rojas, P. Bernstein, and S. Chennupati
J Am Soc Nephrol, 2010. 21: p. 733–735, 2010. doi: 10.1681/ASN.2010010079
In this commentary, the authors discuss the history of sodium polystyrene sulfonate (SPS), and whether the risks outweigh the benefits. Read More

Randomized Clinical Trial of Sodium Polystyrene Sulfonate for the Treatment of Mild Hyperkalemia in CKD.

By Lepage, L., et al.
Clin J Am Soc Nephrol. 2015; 10(12): p. 2136-42.
A randomized, double-blind clinical trial of 33 CKD outpatients with mild hyperkalemia who were randomly assigned to receive either placebo or sodium polystyrene sulfonate (SPS) of 30 g orally one time per day for 7 days. The authors conclude that SPS can lower serum potassium, but admit that the study size was too small to make conclusions about safety. Read More