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REVIEW

CME LEARNING OBJECTIVE: Readers will assess, find the cause of, and treat hyperkalemia
CREDIT
BIFF F. PALMER, MD DEBORAH J. CLEGG, PhD
Professor of Internal Medicine, Professor of Internal Medicine, Biomedi-
Department of Internal Medicine, cal Research Department, Diabetes and
University of Texas Southwestern Obesity Research Division, Cedars-Sinai
Medical Center, Dallas, TX Medical Center, Los Angeles, CA

Diagnosis and treatment
of hyperkalemia
ABSTRACT
Hyperkalemia results either from the shift of potassium
H yperkalemia is common in patients with
cardiovascular disease. Its consequences
can be severe and life-threatening, and its
out of cells or from abnormal renal potassium excretion. management and prevention require a multi-
Cell shift leads to transient increases in the plasma potas- disciplinary approach that entails reducing in-
sium concentration, whereas decreased renal excretion take of high-potassium foods, adjusting medi-
of potassium leads to sustained hyperkalemia. Impair- cations that cause hyperkalemia, and adding
ments in renal potassium excretion can be the result of medications that reduce the plasma potassium
reduced sodium delivery to the distal nephron, decreased concentration. With this approach, patients at
mineralocorticoid level or activity, or abnormalities in the high risk can receive the cardiorenal benefits
cortical collecting duct. In some instances, all 3 of these of drugs that block the renin-angiotensin-al-
dosterone system without developing hyperka-
perturbations are present. Excessive intake of potassium lemia.
can cause hyperkalemia but usually in the setting of
impaired renal function. We discuss the clinical manifes- ■■ 98% OF POTASSIUM IS INSIDE CELLS
tations of hyperkalemia and outline an approach to its
The body of a typical 70-kg man contains
diagnosis and treatment.
about 3,500 mmol of potassium, 98% of which
KEY POINTS is in the intracellular space; the remaining 2%
is in the extracellular space. This large intra-
Exclude pseudohyperkalemia in patients who have a cellular-to-extracellular gradient determines
normal electrocardiogram and no risk factors for the the cell voltage and explains why disorders in
development of hyperkalemia. plasma potassium give rise to manifestations in
excitable tissues such as the heart and nervous
Decreased distal delivery of sodium, reduced mineralo- system.
corticoid levels or activity, and a distal tubular defect are The most important determinants of po-
tassium distribution between the intracellular
causes of impaired renal potassium secretion.
and extracellular space are insulin and beta-
adrenergic receptor stimulation.
Medical conditions and medications that alter the renin- Maintenance of total-body potassium con-
angiotensin-aldosterone system can give rise to hyperka- tent is primarily the job of the kidneys, with
lemia. a small contribution by the gastrointestinal
tract.1,2 Hyperkalemia is most commonly en-
countered in patients with decreased kidney
function.
The normal kidney can secrete a large
amount of potassium, making hyperkalemia
uncommon in the absence of kidney disease.
This large capacity may have evolved to han-
doi:10.3949/ccjm.84a.17056 dle the diet of Paleolithic humans, which con-
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PALMER AND CLEGG

tained 4 times as much potassium as contem- TABLE 1
porary diets.3,4 With the onset of agriculture,
dietary intake of potassium has progressively Causes of hyperkalemia
declined while sodium intake has risen. A
popular theory suggests this mismatch be- Pseudohyperkalemia
tween the modern diet and the nutritional Cellular redistribution
requirements encoded in the human genome Mineral acidosis
during evolution may contribute to chronic Hypertonicity
diseases such as hypertension, stroke, kidney Insulin deficiency
stones, and bone disease.5 Beta-blockers (impair cell uptake of potassium)
Alpha adrenergic stimulation
Hyperkalemic periodic paralysis
■■ MANY POTENTIAL CAUSES
Cell injury
OF HYPERKALEMIA
Excess intake
Causes of hyperkalemia are outlined in Table (almost always in setting of impaired renal
1. Shifting of potassium from the cells to the potassium excretion)
extracellular space is a cause of transient hy-
perkalemia, while chronic hyperkalemia in- Decreased renal excretion
dicates an impairment in renal potassium se- Decreased distal delivery of sodium (oliguric renal
cretion. The following discussion is a guide to failure)
Mineralocorticoid deficiency
the approach to the hyperkalemic patient. Defect of cortical collecting tubule
Is the patient’s hyperkalemia
really pseudohyperkalemia? due to increased fragility or altered sodium-
Pseudohyperkalemia, an artifact of measure- potassium ATPase pump activity.7 This phe-
ment, occurs due to mechanical release of po- nomenon is unusual but occurs because the
tassium from cells during phlebotomy or speci- cells are so fragile.
men processing.6 This diagnosis is made when A spurious increase in plasma potassium
the serum potassium concentration exceeds concentration along with a low plasma cal- Hyperkalemia
the plasma potassium concentration by more cium concentration raises the possibility of is most common
than 0.5 mmol/L, and should be considered calcium chelation and release of potassium in
when hyperkalemia occurs in the absence of a a sample tube contaminated with the antico- in patients
clinical risk factor. Fist-clenching, application agulant ethylenediaminetetraacetic acid. with decreased
of a tight-fitting tourniquet, or use of small-
bore needles during phlebotomy can all cause Is there increased potassium intake?
kidney function
pseudohyperkalemia. Increased potassium intake is a potential cause
Mechanism of pseudohyperkalemia. Since of hyperkalemia in patients with decreased
serum is the liquid part of blood remaining after kidney function or adrenal disease.
coagulation, release of potassium from cells in- Foods naturally rich in potassium include
jured during the process of coagulation raises bananas (a medium-sized banana contains
the potassium level in the serum. Plasma is the 451 mg or 12 mmol of potassium) and po-
cell-free part of blood that has been treated tatoes (844 mg or 22 mmol in a large baked
with anticoagulants; it has no cells that can potato with skin). Other potassium-rich foods
be injured and release potassium. Thus, the are melons, citrus juice, and avocados. Less-
serum potassium level will be higher than that obvious food sources include raw coconut
in the plasma. juice (potassium concentration 44.3 mmol/L)
Reverse pseudohyperkalemia, in contrast, and noni juice (56 mmol/L).
occurs when the plasma potassium level is Salt substitutes, recommended to hyper-
falsely elevated but the serum value is normal. tensive patients with chronic kidney disease,
This situation has been described in hemato- can be a hidden source of dietary potassium.
logic disorders characterized by pronounced Clay ingestion is a potential cause of dys-
leukocytosis in which malignant cells are kalemia. White clay consumption causes hy-
prone to lysis with minimal mechanical stress pokalemia due to potassium binding in the
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HYPERKALEMIA

gastrointestinal tract. Red clay or river bed In contrast, organic acidosis (due to lactic,
clay, on the other hand, is enriched in potas- beta-hydroxybutyric, or methylmalonic acid)
sium (100 mmol of potassium in 100 g of clay) tends not to cause a potassium shift, since most
and can cause life-threatening hyperkalemia organic anions readily cross the cell mem-
in patients with chronic kidney disease.8 brane along with hydrogen. Lactic acidosis is
Eating burnt match heads. Some indi- often associated with potassium shift, but this
viduals chew and ingest burnt match heads, effect is due to loss of cell integrity as a result
a condition called cautopyreiophagia. In one of cell ischemia. The hyperkalemia typically
reported case,9 this activity contributed an ad- present on admission in patients with diabetic
ditional 80 mmol of daily potassium intake in ketoacidosis is the result of insulin deficiency
a dialysis patient, resulting in a plasma potas- and hypertonicity and not the underlying or-
sium concentration of 8 mmol/L. ganic acidosis.10
Hypertonic states can cause hyperkalemia
Is the hyperkalemia the result due to cell shift. For example, hyperglycemia,
of a cellular shift? as in diabetic ketoacidosis, pulls water from
Acute hyperkalemia can be the result of re- the intracellular into the extracellular com-
distribution of cellular potassium. Shifting of partment, thereby concentrating intracellu-
as little as 2% of the body’s potassium from lar potassium and creating a more favorable
the intracellular to the extracellular space can gradient for potassium efflux through mem-
double the plasma potassium concentration. brane channels. This same effect can occur in
Tissue injury. Hyperkalemia frequently neurosurgical patients given large amounts of
occurs in diseases that cause tissue injury such hypertonic mannitol. Repetitive doses of im-
as rhabdomyolysis, trauma, massive hemolysis, munoglobulin can lead to extracellular accu-
and tumor lysis. mulation of sorbitol, maltose, or sucrose, since
Insulin deficiency. Insulin and catechol- these sugars are added to the preparations to
amines are major regulators of potassium prevent immunoglobulin aggregation.11
distribution within the body. After a meal,
The Paleolithic release of insulin not only regulates the plas- Is a disturbance in renal potassium
ma glucose concentration, it also causes po- excretion present?
diet contained tassium to move into cells until the kidneys Sustained hyperkalemia is more commonly as-
4 times as much have had sufficient time to excrete the dietary sociated with decreases in renal potassium ex-
potassium potassium load and reestablish total-body po- cretion than with a cellular shift. In most in-
tassium content. stances the clinician can distinguish between
as ours Exercise, beta-blockers. During exercise, cell shift and impaired renal excretion based
potassium is released from skeletal muscle on the available clinical data.
cells and accumulates in the interstitial com- The transtubular potassium gradient has
partment, where it exerts a vasodilatory effect. been used to determine whether there is a dis-
The simultaneous increase in circulating cat- turbance in renal potassium excretion and to
echolamines regulates this release by promot- assess renal potassium handling.12
ing cell potassium uptake through beta-adren-
ergic receptor stimulation. Transtubular potassium gradient =
Metabolic acidosis can facilitate exit (ie, [urine potassium concentration /
shift) of potassium from cells, but this effect (urine osmolality / serum osmolality)] /
depends on the type of acidosis. Hyperchlo- serum potassium concentration
remic normal anion gap acidosis (mineral
acidosis) most commonly causes this effect This calculation is based on the assump-
due to the relative impermeability of the cell tion that only water is reabsorbed past the
membrane to the chloride anion. As hydrogen cortical collecting duct, and not solutes. It has
ions move into the cell due to accumulation fallen out of favor since we have found this
of ammonium chloride or hydrogen chloride, assumption to be incorrect; a large amount
electrical neutrality is maintained by potas- of urea is reabsorbed daily in the downstream
sium exit. medullary collecting duct as a result of intra-
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PALMER AND CLEGG

renal recycling of urea. In contrast, in nonoliguric patients, the re-
The one situation in which the transtu- nal injury tends to be less severe, and enough
bular potassium gradient may be of use is de- sodium and water are usually delivered distally
termining whether hyperkalemia is a result of to prevent hyperkalemia.
low aldosterone levels as opposed to aldoste- In chronic kidney disease, nephron drop-
rone resistance. One can compare the trans- out and reduction in collecting tubule mass
tubular potassium gradient before and after a also lead to a global decline in distal potassium
physiologic dose (0.05 mg) of 9-alpha fludro- secretion. However, this is countered by an in-
cortisone. An increase of more than 6 over a creased capacity of the remaining individual
4-hour period favors aldosterone deficiency, nephrons for potassium secretion. High flow,
whereas smaller changes would indicate aldo- increased distal sodium delivery, and increased
sterone resistance. activity and number of sodium-potassium
24-hour potassium excretion, spot urine ATPase pumps in the remaining nephrons ac-
potassium-creatinine ratio. A better way to count for this increased secretory capacity.14
assess renal potassium handling is to measure As renal function declines over time, colonic
the amount of potassium in a 24-hour urine potassium secretion progressively increases.15
collection or determine a spot urine potassi- These adaptive changes help to keep the
um-creatinine ratio. A 24-hour urinary po- plasma potassium concentration within the
tassium excretion of less than 15 mmol or a normal range until the glomerular filtration
potassium-creatinine ratio less than 1 suggests rate falls to less than 10 or 15 mL/min. De-
an extrarenal cause of hypokalemia. A ratio velopment of hyperkalemia with more mod-
greater than 20 would be an appropriate renal est reductions in the glomerular filtration rate
response to hyperkalemia. suggest decreased mineralocorticoid activity
One or more of 3 abnormalities should be or a specific lesion of the tubule.
considered in the hyperkalemic patient with
impaired renal excretion of potassium: Mineralocorticoid deficiency
• Decreased distal delivery of sodium Decreased mineralocorticoid levels or activity
• Mineralocorticoid deficiency due to disturbances in the renin-angiotensin- Hyperkalemia
• Abnormal cortical collecting tubule function.13 aldosterone system will impair renal potassium
secretion. Such disturbances can be the result is a frequent
Decreased distal delivery of sodium of diseases or drugs (Figure 1).13,16,17 problem
Under normal circumstances, potassium is Aldosterone deficiency can occur alone or when oliguria
freely filtered across the glomerulus and then in combination with decreased cortisol levels.
mostly reabsorbed in the proximal tubule and Destruction of the adrenal glands is suggested is present
thick ascending limb. Potassium secretion be- when both hormones are reduced. Enzyme
gins in the distal convoluted tubule and in- defects in cortisol metabolism can result in
creases in magnitude into the collecting duct. either isolated deficiency of aldosterone or
Tubular secretion is the component of potas- adrenogenital syndromes associated with de-
sium handling that varies and is regulated ac- creased mineralocorticoid activity.
cording to physiologic needs. Heparin administration leads to a revers-
In acute kidney injury, the rapid decline ible defect in adrenal synthesis of aldosterone.
in glomerular filtration rate and reduction in Drugs that block the stimulatory effect of an-
functioning nephron mass lead to decreased giotensin II on the zona glomerulosa cells of
distal potassium secretion. the adrenal gland will lower aldosterone.
Hyperkalemia is a frequent problem when Renin-angiotensin-aldosterone system
oliguria is present, since the reduction in dis- blockers. Angiotensin-converting enzyme in-
tal delivery of sodium and water further im- hibitors block the formation of angiotensin II,
pairs potassium secretion. Patients with oligu- whereas angiotensin II receptor blockers pre-
ric acute kidney injury are more likely to have vent angiotensin II from binding to its adrenal
a more severe underlying disease state, and receptor. The direct renin inhibitor aliskiren
therefore tissue breakdown and catabolism lowers angiotensin II levels by blocking the
further increase the risk of hyperkalemia. enzymatic activity of renin and lowers the cir-
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HYPERKALEMIA

Angiotensin-converting
enzyme inhibitors Angiotensin II receptor
Direct renin inhibitor blockers

NSAIDs
Beta-blockers
Cyclosporine, tacrolimus Angiotensin I Angiotensin II Adrenal gland
Diabetes
Elderly
Renin
Impaired release Impaired aldosterone
of renin metabolism
Adrenal disease
Heparin
Collecting Ketoconzaole
duct
(–)
Aldosterone

(–) +
Na+
+
+ +
(–) + +
+ Aldosterone receptor
+
+ blockers
+
Na+ channel (–) +
+
Spironolactone
blockers Eplerenone
K+ +
Amiloride Drospirenone
K+
+
Triamterene Aldosterone
Trimethoprim K+ K+
K+
receptor
Pentamidine (–)
K+ K+  CCF
K+ ©2017
Medical Illustrator: David Schumick

Figure 1. A number of pharmacologic agents and conditions can interfere with the renin-angiotensin-
aldosterone system, altering renal potassium excretion. Reabsorption of sodium in the collecting duct
increases the luminal electronegativity, providing a more favorable gradient for potassium secretion.
Aldosterone is critical for this reabsorptive process. A number of drugs and conditions interfere with the
production of aldosterone and, as a result, reduce renal potassium secretion. In some patients, more than
1 disturbance may be present. NSAIDs = nonsteroidal anti-inflammatory drugs.
Based on information in Palmer BF. A physiologic-based approach to the evaluation of a patient with hyperkalemia. Am J Kidney Dis 2010; 56:387–393.

culating levels of both angiotensin I and II.16 Calcineurin inhibitors impair potassium
The syndrome of hyporeninemic hypoal- secretion by suppressing renin release and by
dosteronism is a common cause of hyperkale- direct tubular effects.19
mia in patients who have a glomerular filtra- Beta-blockers. Beta-1 and to a lesser ex-
tion rate between 40 and 60 mL/min. Diabetic tent beta-2 receptor blockade can also result
nephropathy and interstitial renal disease are in a hyporeninemic state.
the most common clinical entities associated
with this syndrome.10 Other causes include Distal tubular defect
analgesic nephropathy, urinary tract obstruc- Hyperkalemia can result from interstitial renal
tion, sickle cell disease, systemic lupus erythe- diseases that specifically affect the distal neph-
matosus, and amyloidosis. ron. In this setting, the glomerular filtration
Nonsteroidal anti-inflammatory drugs can rate is only mildly reduced, and circulating al-
cause hyperkalemia by suppressing renin re- dosterone levels are normal.
lease and reducing delivery of sodium to the Renal transplant, lupus erythematosus,
distal nephron.18 amyloidosis, urinary obstruction, and sickle
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PALMER AND CLEGG

cell disease are conditions in which an im-
pairment in renin release may coexist with a Depressed ST segment
defect in tubular secretion. Hypokalemia Diphasic T wave
Potassium-sparing diuretics impair the Prominent U wave
ability of the cortical collecting tubule to se-
crete potassium. Specifically, amiloride and
triamterene inhibit sodium reabsorption me- Normal
diated by the epithelial sodium channel lo-
cated on the apical membrane of the principal
cell. This effect abolishes the lumen’s nega- Peaked T wave
tive potential and thereby removes a driving
force for potassium secretion.
Trimethoprim and pentamidine cause Increasing Wide PR interval
similar effects. severity of Wide QRS duration
Spironolactone and eplerenone compete hyperkalemia Peaked T wave
with aldosterone at the level of the mineralo-
corticoid receptor and can result in hyperka- Loss of P wave
lemia. Sinusoidal wave
Drospirenone, a non-testosterone-derived
Figure 2. Electrocardiographic signs of hyperkalemia
progestin contained in certain oral contracep-
tives, possesses mineralocorticoid-blocking
effects similar to those of spironolactone. • Widening of the QRS interval
The plasma potassium level should be • Loss of the P wave
monitored when these drugs are prescribed • A sine-wave pattern—an ominous de-
in patients receiving potassium supplements, velopment and a harbinger of impending
renin-angiotensin-aldosterone system block- ventricular fibrillation and asystole.
ers, or nonsteroidal anti-inflammatory drugs.20 The plasma potassium concentration often
correlates poorly with cardiac manifestations. The plasma
■■ CLINICAL FEATURES OF HYPERKALEMIA In a retrospective review, only 16 of 90 cases
met strict criteria for electrocardiographic potassium
Neuromuscular manifestations of hyperkale- changes reflective of hyperkalemia (defined concentration
mia include paresthesias and fasciculations in as new peaked and symmetric T waves that
the arms and legs. Severe elevation in potas- resolved on follow-up).22 In 13 of these cas- often correlates
sium can give rise to an ascending paralysis es, the electrocardiogram was interpreted as poorly with
with eventual flaccid quadriplegia. Typically, showing no T-wave changes even when read
the trunk, head, and respiratory muscles are cardiac
by a cardiologist. In addition, electrocardio-
spared, and respiratory failure is rare. graphic criteria for hyperkalemia were noted manifestations
Cardiac signs in only 1 of 14 patients who manifested ar-
Hyperkalemia has depolarizing effects on the rhythmias or cardiac arrest attributed to in-
heart that are manifested by changes in the creased plasma potassium concentration.
electrocardiogram (Figure 2). The progres-
sive changes of hyperkalemia are classically ■■ TREATMENT OF ACUTE HYPERKALEMIA
listed as: The treatment of hyperkalemia depends on
• Peaked T waves that are tall, narrow, and the magnitude of increase in the plasma po-
symmetrical and can occasionally be con- tassium concentration and the presence or
fused with the hyperacute T-wave change absence of electrocardiographic changes or
associated with an ST-segment elevation neuromuscular symptoms.23 Acute treatment
myocardial infarction.21 However, in the is indicated for marked electrocardiographic
latter condition, the T waves tend to be changes and severe muscle weakness.
more broad-based and asymmetric in shape. Intravenous calcium rapidly normalizes
• ST-segment depression membrane excitability by antagonizing the
• Widening of the PR interval potassium-induced decrease in membrane ex-
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HYPERKALEMIA

TABLE 2
Reducing the risk of hyperkalemia when using
renin-angiotensin-aldosterone system blockers
Assess renal function to define overall risk of hyperkalemia
Discontinue medications that can impair renal potassium excretion, including herbal preparations and over-
the-counter nonsteroidal anti-inflammatory drugs
Reduce potassium in diet, avoid salt substitutes containing potassium
Ensure effective diuretic therapy (loop diuretics should be used if the estimated glomerular filtration rate
is < 30 mLmin/1.73 m2)
Correct metabolic acidosis when present
Start with low doses of renin-angiotensin-aldosterone system blockers and monitor closely

citability but does not alter the plasma potas- may be a hidden source of dietary potassium.
sium concentration. Dietary counseling. Patients should be
Insulin lowers the plasma potassium con- instructed to reduce their dietary intake of po-
centration by promoting its entry into cells. tassium and to avoid salt substitutes that con-
To avoid hypoglycemia, 10 units of short-act- tain potassium.
ing insulin should be accompanied by a 50-g Diuretic therapy is beneficial in minimiz-
infusion of glucose, increased to 60 g if 20 ing hyperkalemia in patients with chronic
units of insulin are given.24 kidney disease. Thiazide and loop diuretics en-
Beta-2 receptor agonists produce a similar hance renal potassium excretion by increasing
effect. The shift of potassium into cells with flow and delivery of sodium to the collecting
insulin and beta-2-adrenergic receptor stimu- duct. Thiazide diuretics are effective when the
Acute lation is brought about by increases in sodium- estimated glomerular filtration rate is greater
treatment potassium ATPase pump activity, primarily in than 30 mL/min, while loop diuretics should
is indicated skeletal muscle cells. be used in patients with more severe renal in-
Sodium bicarbonate, in the absence of sufficiency (Table 2).
for marked acidosis, lowers the plasma potassium con- Sodium bicarbonate is an effective agent
electrocardio- centration only slightly. It should be reserved to minimize increases in the plasma potassium
for hyperkalemic patients who have coexist- concentration in patients with chronic kidney
graphic ing metabolic acidosis after the patient has disease and metabolic acidosis. This drug in-
changes and received insulin and glucose, an adrenergic creases renal potassium excretion by increas-
agent, and calcium. ing distal sodium delivery and shifts potassium
severe muscle into cells as the acidosis is corrected. The
These acute treatments need to be fol-
weakness lowed by therapies designed to lower the to- likelihood of developing volume overload as
tal body potassium content such as diuretics, a complication of sodium bicarbonate admin-
potassium-binding drugs, and dialysis. istration can be minimized with effective di-
uretic therapy.
■■ TREATMENT OF CHRONIC HYPERKALEMIA
Avoiding hyperkalemia if renin-angiotensin-
Review medications. Once the diagnosis of aldosterone system blockers are needed
hyperkalemia has been made, the initial ap- Renin-angiotensin-aldosterone system block-
proach should be to review the patient’s medi- ers can be problematic, as these drugs cause
cations and make every effort to discontinue hyperkalemia, often in the very patients who
drugs that can impair renal potassium excre- derive the greatest cardiovascular benefit from
tion.16 Patients should be asked about their use them.16 A number of steps can reduce the risk
of over-the-counter nonsteroidal anti-inflam- of hyperkalemia and allow these drugs to be
matory drugs and herbal remedies, since herbs used.
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PALMER AND CLEGG

The initial dose should be low and the plasma potassium concentration in the setting
plasma potassium should be measured within of ongoing use of renin-angiotensin-aldoste-
1 to 2 weeks after drug initiation. If the potas- rone system blockers.
sium level is normal, the dose can be titrated Patiromer is a nonabsorbed polymer ap-
upwards with remeasurement of the plasma proved for clinical use to treat hyperkalemia.
potassium after each dose titration. If the The drug binds potassium in exchange for
plasma potassium concentration rises to 5.5 calcium in the gastrointestinal tract, predomi-
mmol/L, in some cases lowering the dose will nantly in the colon, and lowers the plasma
reduce the potassium concentration and allow potassium concentration in a dose-dependent
the patient to remain on the drug. manner, with the greatest reduction in those
In patients at risk of hyperkalemia, angio- with higher starting values.27,28
tensin II receptor blockers and direct renin in- Patiromer effectively controlled plasma
hibitors should be used with the same caution potassium concentrations in a 1-year ran-
as angiotensin-converting enzyme inhibitors. domized trial in high-risk patients on renin-
If the plasma potassium concentration ex- angiotensin-aldosterone system blockers.29
ceeds 5.5 mmol/L despite the above precau-
The main adverse events in clinical trials
tions, one can consider using a potassium-bind-
have been constipation and hypomagnesemia,
ing drug (see below) before deciding to avoid
which required magnesium replacement in a
renin-angiotensin-aldosterone system blockers.
Sodium polystyrene sulfonate binds small number of patients, but overall, the drug
potassium in the gastrointestinal tract in is well tolerated.
exchange for sodium and has been used to Sodium zirconium cyclosilicate is a non-
manage hyperkalemia. This drug is most absorbed microporous compound that binds
commonly given along with sorbitol as a potassium in exchange for sodium throughout
therapy for acute hyperkalemia. Although the gastrointestinal tract. It has been found ef-
the drug is widely used, most of the potas- fective in lowering plasma potassium concen- Use loop
sium-lowering effect is due to an increase in tration in a dose-dependent fashion in high- diuretics,
stool volume caused by sorbitol.25,26 In addi- risk patients, most of whom were receiving
tion, long-term use is poorly tolerated, and renin-angiotensin-aldosterone system block- not thiazides,
the drug has been linked to gastrointestinal ers.30–32 Adverse events were generally com- if the estimated
toxicity in rare cases. parable to those with placebo in clinical tri- glomerular
Patiromer and sodium zirconium cyclosili- als; however, edema occurred more frequently
cate are two new potassium-binding drugs that when higher doses were used. This drug is not filtration rate
have been shown to be effective in reducing yet approved for clinical use. ■ is < 30 mL/min
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942  CLEV ELA N D C LI N I C JOURNAL OF MEDICINE   VOL UME 84  •  N UM BE R 12   DE CE M BE R  2017