REVIEW

CURRENT
OPINION Advances in the management of hyperkalemia in
chronic kidney disease
Andrea C.J. Cowan a, Elie G. Gharib a, and Matthew A. Weir a,b,c

Purpose of review
Patients with chronic kidney disease (CKD) have an increased risk of hyperkalemia that increases both
short-term and long-term mortality. Historically, managing hyperkalemia has relied upon dietary
modifications, augmentation of urinary potassium excretion and enhanced enteral potassium elimination.
This review discusses current treatments and their limitations and summarizes the evidence supporting novel
agents for potassium lowering in patients with CKD.
Recent findings
The introduction of two novel ion exchange resins represents the first new pharmacologic therapies for
hyperkalemia in the last 50 years. Patiromer, which was recently approved for use in the United States, has
been shown to be well tolerated and effective for decreasing serum potassium in patients with CKD when
taken for up to a year. Sodium zirconium cyclosilicate for which approval is pending has also shown
promise in treating both acute and chronic hyperkalemia in patients with CKD. Both medications have
been well tolerated with minimal adverse events in relatively short-term follow-up.
Summary
Novel ion exchange resins have the potential to provide new strategies for safely and effectively managing
hyperkalemia in the CKD population. This may decrease morbidity and mortality associated with
hyperkalemia and allow more broad use of medications whose use is otherwise limited by hyperkalemia.
Keywords
chronic kidney disease, hyperkalemia, Patiromer, Sodium zirconium cyclosilicate

INTRODUCTION commonly associated with CKD can limit their

Hyperkalemia is a common metabolic complication
of chronic kidney disease (CKD). It arises from CKD
itself, its comorbid conditions and the medications
used to manage CKD. Hyperkalemia increases
patient mortality directly and can limit the use of
important medications.
The incidence of hyperkalemia varies depending
on the patient population studied and how it is
defined; however, it becomes significantly more
prevalent as estimated glomerular filtration rate
(eGFR) drops below 40 ml/min [1]. Although hyper-
kalemia complicates between 2 and 3% of all hos-
pital admissions [2], this increases significantly in
the CKD population, in which the incidence has
been found as high as 31.5% among outpatients
with an eGFR less than 20 ml/min [3]. Decreasing
GFR and impaired sodium delivery to the distal
nephron both limit renal potassium excretion in
patients with CKD. Although eukalemia can be
maintained in mild-to-moderate CKD through a
number of compensatory mechanisms, conditions
effectiveness [4,5]. Diabetes mellitus is associated
with both hyporeninemic hypoaldosteronism,
which limits renal potassium excretion, and insulin
deficiency, which causes extracellular potassium
shifts. Heart failure can also impair potassium
excretion by decreasing distal sodium delivery [4,6].
Therapeutic interventions for CKD can further
exacerbate hyperkalemia. Inhibition of the renin–
angiotensin–aldosterone system (RAAS) is import-
ant for patients with proteinuric CKD, heart failure
and hypertension [7]. However, angiotensin-
converting enzyme (ACE) inhibitors and AT1
a
Department of Medicine, Schulich School of Medicine and Dentistry,
b
Institute of Clinical Evaluative Sciences and cFaculty of Epidemiology
and Biostatistics, Western University, London, Ontario, Canada
Correspondence to Matthew A. Weir, University Hospital, 339 Wind-
ermere Road, A10-213, London, ON, Canada N6A 5A5. Tel: +1 519 663
2998; fax: +1 519 663 3449; e-mail: matthew.weir@lhsc.on.ca
Curr Opin Nephrol Hypertens 2017, 26:235–239
DOI:10.1097/MNH.0000000000000320

1062-4821 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved. www.co-nephrolhypertens.com

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Epidemiology and prevention
KEY POINTS
 Hyperkalemia is a common issue found with patients
with chronic kidney disease that is associated with
increased mortality both acutely and in long term.
 Current management strategies for hyperkalemia are
limited by patient compliance, limited effectiveness and
safety concerns.
 Novel ion exchange resins such as Patiromer and
Sodium zirconium cyclosillcate (ZS-9) have been shown
in clinical trials to effectively manage hyperkalemia in
chronic kidney disease patients on a long-term basis
and have a favorable side effect profile.
blockers (ARBs) associate with increased rates of
hyperkalemia, which often prevents their use or
limits their dose [8–10]. Mineralocorticoid receptor
antagonists are also indicated for some patients with
CKD and associate with risk of hyperkalemia, com-
plicating and limiting their use in these patients
[11].
The need to keep potassium levels below critical
levels is well understood; however, even moderate
levels of hyperkalemia are associated with poor out-
comes. Increases in both short-term and long-term
mortality have been demonstrated in patients with a
potassium levels greater than 5.5 mmol/l [8,12,13].
This evidence underscores the delicate balance that
clinicians’ must achieve when trying to apply appro-
priate therapies while minimizing the risk of hyper-
kalemia in a population of patients already
predisposed to it. In this review, we discuss the
options for outpatient management of hyperkale-
mia with a focus on novel therapies for enhanced
enteral elimination of potassium.
OUTPATIENT MANAGEMENT OF
HYPERKALEMIA
The acute treatment of hyperkalemia focuses prim-
arily on the translocation of potassium from the
extracellular space to the intracellular space, provid-
ing a temporary decrease in the serum concen-
tration of potassium [14]. Treatments commonly
used for severe hyperkalemia, such as intravenous
calcium, insulin, sodium bicarbonate and inhaled b-
adrenergic agonists, do not eliminate excess potass-
ium and are not typically feasible in the outpatient
setting [9,15]. Rather, the control of serum potass-
ium concentrations among outpatients with CKD
involves limitation of potassium intake, augmenta-
tion of urinary excretion and enteral elimination
using exchange resins.
236 www.co-nephrolhypertens.com
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
DIETARY POTASSIUM RESTRICTION
In patients with less-severe chronic hyperkalemia,
an important early intervention is to limit potass-
ium intake. Low-potassium diets can be restrictive
and difficult to follow [16], but lists of potassium-
rich foods are widely available [17], and dieticians
with expertise in CKD can uncover dietary potass-
ium sources and improve adherence. In patients
with persistent hyperkalemia, less-common dietary
sources of potassium should also be considered such
as salt substitutes [18], herbal remedies [19] and low
potassium foods that may be consumed in large
quantities such as strawberries or grapes.
AUGMENTATION OF URINARY
POTASSIUM EXCRETION
When dietary restriction is not effective, increasing
the urinary excretion of potassium may be necess-
ary. This can be accomplished by cessation or dose-
reduction of drugs associated with potassium
retention or by adding potassium-wasting drugs.
Commonly used drugs associated with potassium
retention include RAAS inhibitors such as ACE
inhibitors, ARBs and mineralocorticoid receptor
antagonists. Other less commonly used drugs that
affect potassium excretion include calcineurin
inhibitors and NSAIDs that inhibit renin release,
heparin and ketoconazole that inhibit the pro-
duction of aldosterone, and potassium-sparing
diuretics, trimethoprim and pentamidine that blunt
the effect of aldosterone on the collecting duct
[20–22]. Although reducing the doses of these medi-
cations may restore serum potassium concen-
trations to normal, their beneficial effects may be
lost as a consequence. Alternatively, potassium
excretion can be enhanced by loop diuretics alone
or in combination with thiazide diuretics, but these
drugs are only appropriate in the right clinical con-
text and their effectiveness diminishes as CKD
advances [23].
ENHANCED ENTERAL POTASSIUM
ELIMINATION
Eliminating excess potassium via the gastrointesti-
nal tract is an attractive option because it can allow
continued use of RAAS inhibitors at adequate doses.
A commonly used agent for promoting enteral pot-
assium excretion is the nonspecific polymeric
exchange resin sodium polystyrene sulfonate (SPS)
[24]. Although previously in popular use, its niche in
the treatment of hyperkalemia is uncertain [25].
This uncertainty arises from its only moderate effec-
tiveness and potential adverse effects. Although
some studies have demonstrated significant
Volume 26  Number 3  May 2017

reductions in serum potassium with SPS [26,27],
these studies were uncontrolled, and more recent
studies have failed to confirm their findings [28]. In
the past, SPS was frequently administered with 70%
sorbitol to avoid constipation and to enhance
potassium elimination, but the combination of
these two agents has been associated with serious,
even fatal gastrointestinal complications, which led
the US Food and Drug Administration to recom-
mend avoiding its use in 2009 [29]. SPS is now
administered with lower concentrations of sorbitol
but it continues to be associated with serious adverse
gastrointestinal reactions, although the incidence
appears to be low [30,31]. Despite the problems with
SPS, the concept of achieving adequate levels of
RAAS blockade while eliminating excess potassium
via the gastrointestinal tract remains an attractive
one. Therefore, there is a need for a novel, effective
and well tolerated mechanism to enhance enteral
potassium elimination.
Patiromer
Patiromer, Relypsa, Inc. Redwood City, California,
USA. is an ion exchange resin that was approved in
November 2015. It is a nonabsorbable polymer bead
that acts in the colon to bind potassium in exchange
for calcium and promote fecal potassium excretion.
A number of studies have examined its safety and
efficacy in populations at risk of hyperkalemia. The
first randomized controlled trial was PEARL-HF that
studied patients with heart failure and high-normal
potassium (4.3–5.1 mmol/l) and a predisposing fac-
tor for hyperkalemia: either CKD with a GFR less
than 60 ml/min/1.73 m2 or hyperkalemia requiring
cessation of ACE inhibitors, ARBs or beta blockers
[32]. Patients were then initiated on spironolactone,
a potassium-sparing diuretic and either patiromer or
a placebo. This study showed a statistically signifi-
cant reduction in serum potassium levels in the
patiromer group over the 28-day follow-up period,
and a larger number of participants tolerated an
increase in the spironolactone dose from 25 to
50 mg. A subgroup analysis of patients with an
eGFR less than 60 ml/min/1.73 m2 showed similar
findings.
AMETHYST was the first trial to demonstrate
patiromer’s efficacy in an exclusively CKD popu-
&
lation [33 ]. Patients with diabetes, stages 3–4
CKD (eGFR 15–60 ml/min/1.73 m2) and preexisting
hyperkalemia or hyperkalemia after an increase in
losartan were started on patiromer at doses ranging
from 4.2 to 16.8 g twice daily and followed for 52
weeks. Compared with placebo, patiromer produced
a statistically significant decrease in serum potass-
ium from baseline as early as 48 h after initiation.
1062-4821 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Hyperkalemia and chronic kidney disease Cowan et al.
When the study drug was withdrawn at the end of
the study period, there was a significant increase in
serum potassium within 3 days indicating the need
for ongoing therapy.
The largest study of patiromer in the CKD popu-
lation included 243 patients with stages 3–4 CKD
and serum potassium of 5.1–6.6 mmol/l who had
been stable on all medications including RAAS
&&
blockade and diuretics for 28 days [34 ]. All patients
completed a 4-week run-in on patiromer and were
then randomized to received placebo or patiromer
for 8 weeks. Patiromer decreased serum potassium
levels significantly and increased the number of
patients who were able to continue on RAAS inhi-
bition during the 8-week study period. For patients
randomized to the placebo, there was a significant
increase in serum potassium after the withdrawal of
patiromer following the 4-week run-in.
The safety profile of patiromer was similar in all
three studies. The most common adverse event was
constipation that leads to patiromer discontinu-
& &&
ation in 6–9% of patients [32,33 ,34 ]. Mild hypo-
magnesemia was also observed with a decrease in
serum magnesium of up to 0.1 mmol/l compared
with placebo; however, no patients developed
& &&
severe hypomagnesmia [32,33 ,34 ]. Hypokalemia
was also more common in treatment groups with
5% of participants experiencing a serum potassium
less than 3.8, which resolved with drug withdrawal
&&
[34 ]. The AMETHYST trial also found a 9.2% rate of
worsening of CKD among patients treated with
patiromer, although it is difficult to tell if this was
secondary to drug effect, progression of CKD or
because of the increased doses of RAAS blockade
&
used in the treatment arm [33 ]. Finally, patiromer
has been shown to bind and prevent absorption of
many other medications in animal models, which
prompted the FDA to issue a black box warning
stating that it should not be taken within 6 h of
any other medications. Overall, patiromer is a prom-
ising new medication for the treatment of chronic
hyperkalemia in CKD and appears to be well toler-
ated. Although no severe adverse events were
reported in any of the trials, there is no safety data
on patiromer beyond 1 year, and further postmarket
monitoring will be necessary to establish its safety.
Sodium zirconium cyclosilicate
Sodium zirconium cyclosilicate (ZS-9) AstraZeneca
PLC, Cambridge, United Kingdom is another novel
treatment for hyperkalemia that has completed
phase III trials. It acts as a nonabsorbed cation
exchanger that selectively binds potassium in the
gastrointestinal tract. It was evaluated in the HAR-
MONIZE trial that was designed to determine the
www.co-nephrolhypertens.com 237
Epidemiology and prevention
efficacy and safety of zirconium cyclosilicate for up
to 4 weeks in patients with hyperkalemia [35].
Findings demonstrated that zirconium cyclosilicate
was effective both in rapidly lowering potassium to
normal range and maintaining normal potassium
levels for up to 4 weeks in patients with various
degrees of hyperkalemia. The potassium-lowering
effect of zirconium cyclosilicate was consistent
across all patient subgroups and observed 1 h after
the first dose. Normokalemia was achieved in 84%
of the patients within 24 h and 98% within 48 h of
treatment initiation. When compared with placebo,
all three doses of zirconium cyclosilicate resulted in
significantly higher proportions of patients with
normal potassium levels throughout the 28-day
trial. The tolerability profile did not differ signifi-
cantly from that of placebo.
The second large trial involving ZS-9 in patients
with CKD and hyperkalemia used lower dose ranges
than HARMONIZE and followed patients for 14 days
&&
[36 ]. ZS-9 appeared to act as a potent and selective
potassium trap and corrected hyperkalemia within
48 h. A clinically significant treatment effect was
observed within 1 h of administration. The decline
in the potassium level was rapid and dose-depend-
ent and most pronounced in patients with the high-
est potassium levels at baseline. ZS-9 also effectively
normalized potassium levels in patients who were
receiving RAAS inhibitors for the treatment of
cardiovascular or renal disease, and normal serum
potassium levels were maintained with once-daily
&&
doses of 5 or 10 g of ZS-9 [36 ]. The drug was equally
effective across various subgroups, including
patients with a combination of heart failure, CKD
and diabetes.
From a safety standpoint, no clinically signifi-
cant changes in vital signs or serum concentrations
of sodium, calcium or magnesium were observed
[35]. No dose-dependent increase in urinary sodium
excretion was seen. There was a predictably higher
rate of hypokalemia with higher ZS-9 doses but all
episodes were mild.
Despite the promising results for both
patiromer and ZS-9, some limitations still exist.
Patiromer has won FDA approval but the warning
against its use within 6 h of another oral medication
may limit its clinical applicability. In May 2016,
ZS-9 was denied approval by the FDA over ‘obser-
vations arising from a preapproval manufacturing
inspection’ [37]. As of October 2016, ZS-9 has been
submitted to the FDA for reassessment. Finally, all
studies to date have been short in duration and as
such have not been in a position to evaluate the
potential long-term role for these agents in patients
in whom hyperkalemia has prevented adequate
RAAS blockade.
238 www.co-nephrolhypertens.com
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
CONCLUSION
The treatment of chronic hyperkalemia has
remained relatively unchanged since the 1950s.
Limitation of dietary potassium and enhancing its
urinary excretion are the cornerstones of out-
patient therapy for mild-to-moderate hyperkalemia.
Despite its popularity, the role of SPS is limited by
questions over its safety and effectiveness. However,
enteral elimination of potassium has the potential
to change significantly over the coming years with
the introduction of promising new ion exchange
resins. Although further research is needed to
establish the long-term safety profile of these medi-
cations and their effect on clinical outcomes in
patients with CKD, they hold promise for improving
our treatment of hyperkalemia in patients with
CKD.
Acknowledgements
Please note that despite sharing a first and last name,
M.R.W., the primary author of Weir et al. N Engl J Med.
2015 and M.A.W., the supervising author of this review,
have no personal or financial relationship.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Moranne O, Froissart M, Rossert J, et al. Timing of onset of CKD-related
metabolic complications. J Am Soc Nephrol 2009; 20:164–171.
2. Fleet JL, Shariff SZ, Gandhi S, et al. Validity of the International Classification
of Diseases 10th revision code for hyperkalaemia in elderly patients at
presentation to an emergency department and at hospital admission. BMJ
Open 2012; 2:e002011.
3. Sarafidis PA, Blacklock R, Wood E, et al. Prevalence and factors associated
with hyperkalemia in predialysis patients followed in a low-clearance clinic.
Clin J Am Soc Nephrol 2012; 7:1234–1241.
4. Musso CG. Potassium metabolism in patients with chronic kidney disease
(CKD), Part I: patients not on dialysis (stages 3–4). Int Urol Nephrol 2004;
36:465–468.
5. Einhorn LM, Zhan M, Hsu VD, et al. The frequency of hyperkalemia and its
significance in chronic kidney disease. Arch Intern Med 2009; 169:1156–
1162.
6. Lazich I, Bakris GL. Prediction and management of hyperkalemia across the
spectrum of chronic kidney disease. Semin Nephrol 2014; 34:333–339.
7. Remuzzi G, Perico N, Macia M, Ruggenenti P. The role of renin–angiotensin–
aldosterone system in the progression of chronic kidney disease. Kidney Int
Suppl 2005; 68:S57–65.
8. Korgaonkar S, Tilea A, Gillespie BW, et al. Serum potassium and outcomes in
CKD: insights from the RRI-CKD cohort study. Clin J Am Soc Nephrol 2010;
5:762–769.
9. Jain N, Kotla S, Little BB, et al. Predictors of hyperkalemia and death in
patients with cardiac and renal disease. Am J Cardiol 2012; 109:1510–
1513.
10. Raebel MA. Hyperkalemia associated with use of angiotensin-converting
enzyme inhibitors and angiotensin receptor blockers. Cardiovasc Ther
2012; 30:e156–e166.
Volume 26  Number 3  May 2017

11. Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on
proteinuria and kidney function in patients with chronic kidney disease. Kidney
Int 2006; 70:2116–2123.
12. Chen Y, Chang AR, McAdams DeMarco MA, et al. Serum potassium,
mortality, and kidney outcomes in the Atherosclerosis Risk in Communities
Study. Mayo Clin Proc 2016; 91:1403–1412.
13. Hayes J, Kalantar-Zadeh K, Lu JL, et al. Association of hypo- and hyperkalemia
with disease progression and mortality in males with chronic kidney disease:
the role of race. Nephron Clin Pract 2012; 120:c8–c16.
14. Blumberg A, Weidmann P, Ferrari P. Effect of prolonged bicarbonate admin-
istration on plasma potassium in terminal renal failure. Kidney Int 1992;
41:369–374.
15. Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GFM. Aldosterone
antagonists for preventing the progression of chronic kidney disease: a sys-
tematic review and meta-analysis. Clin J Am Soc Nephrol 2009; 4:542–551.
16. Goraya N, Wesson DE. Dietary management of chronic kidney disease:
protein restriction and beyond. Curr Opin Nephrol Hypertens 2012;
21:635–640.
17. National Kidney Foundation. Potassium and your CKD diet. New York:
National Kidney Foundation; 2016; Available from: https://www.kidney.org/
atoz/content/potassium. [Cited 25 November 2016]
18. Ray K, Dorman S, Watson R. Severe hyperkalaemia due to the concomitant
use of salt substitutes and ACE inhibitors in hypertension: a potentially life
threatening interaction. J Hum Hypertens 1999; 13:717–720.
19. Miller LG. Herbal medicinals: selected clinical considerations focusing on
known or potential drug-herb interactions. Arch Intern Med 1998; 158:2200–
2211.
20. Palmer BF. Managing hyperkalemia caused by inhibitors of the renin–angio-
tensin–aldosterone system. N Engl J Med 2004; 351:585–592.
21. Perazella MA. Trimethoprim-induced hyperkalaemia: clinical data, mechanism,
prevention and management. Drug Saf 2000; 22:227–236.
22. Perazella MA. Drug-induced hyperkalemia: old culprits and new offenders. Am
J Med 2000; 109:307–314.
23. Weiner ID, Wingo CS. Hyperkalemia: a potential silent killer. J Am Soc
Nephrol 1998; 9:1535–1543.
24. Kessler C, Ng J, Valdez K, et al. The use of sodium polystyrene sulfonate in the
inpatient management of hyperkalemia. J Hosp Med 2011; 6:136–140.
25. Sterns RH, Rojas M, Bernstein P, Chennupati S. Ion-exchange resins for the
treatment of hyperkalemia: are they safe and effective? J Am Soc Nephrol
2010; 21:733–735.
26. Scherr L, Ogden DA, Mead AW, et al. Management of hyperkalemia with a
cation-exchange resin. N Engl J Med 1961; 264:115–119.
27. Flinn RB, Merrill JP, Welzant WR. Treatment of the oliguric patient with a new
sodium-exchange resin and sorbitol; a preliminary report. N Engl J Med 1961;
264:111–115.
1062-4821 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Hyperkalemia and chronic kidney disease Cowan et al.
28. Gruy-Kapral C, Emmett M, Santa Ana CA, et al. Effect of single dose resin–
cathartic therapy on serum potassium concentration in patients with end-
stage renal disease. J Am Soc Nephrol 1998; 9:1924–1930.
29. Watson M, Abbott KC, Yuan CM. Damned if you do, damned if you don’t:
potassium binding resins in hyperkalemia. Clin J Am Soc Nephrol 2010;
5:1723–1726.
30. Gerstman BB, Kirkman R, Platt R. Intestinal necrosis associated with post-
operative orally administered sodium polystyrene sulfonate in sorbitol. YAJKD
1992; 20:159–161.
31. McGowan CE, Saha S, Chu G, et al. Intestinal necrosis due to sodium
polystyrene sulfonate (Kayexalate) in sorbitol. South Med J 2009; 102:493–
497.
32. Pitt B, Anker SD, Bushinsky DA, et al. Evaluation of the efficacy and safety of
RLY5016, a polymeric potassium binder, in a double-blind, placebo-con-
trolled study in patients with chronic heart failure (the PEARL-HF) trial. Eur
Heart J 2011; 32:820–828.
33. Bakris GL, Pitt B, Weir MR, et al. Effect of patiromer on serum potassium level
& in patients with hyperkalemia and diabetic kidney disease: the AMETHYST-
DN randomized clinical trial. JAMA 2015; 314:151–161.
This was the first trial to demonstrate the efficacy of Patiromer in treating
hyperkalemia in chronic kidney disease patients.
34. Weir MR, Bakris GL, Bushinsky DA, et al. Patiromer in patients with kidney
&& disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med 2015;
372:211–221.
This was the largest study showing that Patiromer can be used to safely treat
hyperkalemia on an ongoing basis. This has important implications for the pos-
sibility of using Patiromer on a chronic basis in kidney disease patients, potentially
to counteract the hyperkalemic effects of other medications.
35. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium
cyclosilicate on potassium lowering for 28 days among outpatients with
hyperkalemia: the HARMONIZE randomized clinical trial. JAMA 2014;
312:2223–2233.
36. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate
&& in hyperkalemia. N Engl J Med 2015; 372:222–231.
This trial demonstrated the ability of sodium zirconium cyclosilicate to acutely lower
potassium and maintain normal levels when taken chronically for up to 2 weeks.
This was seen across a wide spectrum of comorbidities and holds promise for both
acute and chronic potassium management.
37. AstraZeneca receives Complete Response Letter from US FDA for
sodium zirconium cyclosilicate (ZS-9) for oral suspension for treatment of
hyperkalemia. [Internet]. astrazeneca.com. 2016; [cited 15 November 2016].
Available from: https://www.astrazeneca.com/media-centre/press-releases/
2016/astrazeneca-receives-complete-response-letter-from-us-fda-for-sodium-
zirconium-cyclosilicate-zs-9-for-oral-suspension-for-treatment-of-hyperkalaemia-
27052016.html.
www.co-nephrolhypertens.com 239