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INTRODUCTION

Chronically elevated serum potassium levels can significantly impact patient health and resource utilization. In adults, hyperkalemia is defined as a serum potassium level greater than 5.5 mEq/L, though depending on the source, it may also be defined more strictly, as greater than 5.0 mEq/L.^1-3 Still, most laboratories define a normal serum potassium range as 3.5 to 5.5 mEq/L.^1,2 Potassium elevations are commonly associated with diseases, such as chronic kidney disease (CKD), congestive heart failure (CHF), and diabetes mellitus (DM), but may also be caused by certain medications. While treatment has remained unchanged for many years, recent approvals of several medications by the United States Food and Drug Administration (FDA) require this disorder to be revisited.

POTASSIUM HOMEOSTASIS

Potassium is 1 of the most abundant electrolytes in the body and is maintained almost exclusively intracellularly.^1,2 Normal potassium homeostasis is maintained primarily through renal elimination, in that approximately 90% of potassium excretion takes place in the kidney.² Other means of excretion also exist, including excretion through the gastrointestinal tract, sweat, or vomit, though these are involved to a lesser extent.^1,2 Further, homeostasis is impacted by potassium metabolism in the liver and muscles mediated by insulin and aldosterone.¹

Within the kidneys, potassium secretion primarily takes place within the distal nephron, including the distal convoluted tubule, the connecting tubule, and the collecting duct.⁴ The electrochemical gradient created by sodium/potassium adenosine triphosphatase (Na+/K+ ATPase) and luminal sodium channels leads to secretion of excess K+ ions through luminal potassium channels.^4,5

Aldosterone also plays an important role in maintaining potassium homeostasis. In the presence of volume depletion, aldosterone release is triggered by the renin-angiotensin-aldosterone system (RAAS).^1,5 Increasing circulating levels of aldosterone leads to sodium reabsorption through an increase in luminal sodium channels in the collecting tubule and a subsequent increase in potassium excretion.¹ Alternatively, in the presence of hyperkalemia, high potassium levels also trigger aldosterone release, which enhances potassium excretion without affecting the circulating sodium concentration.^1,5 Aldosterone may also increase intestinal potassium excretion.²

Prevalence, Complications, and Impact

The prevalence of hyperkalemia is difficult to define based on several factors. First, studies use various diagnostic thresholds inconsistently to define hyperkalemia.^3,6 Additionally, differences in prevalence are seen when researchers change the number of blood samples required to make a diagnosis.³ Regardless, some estimates are available.

Chronic hyperkalemia is rare in the community-dwelling population, with an estimated prevalence of 1.57% in 2014.³ The likelihood of developing hyperkalemia increases with age, such that those over the age of 85 years are almost 20 times more likely to receive this diagnosis compared with those under the age of 20.³ The prevalence of hyperkalemia is also significantly higher in those with CKD, and, as the disease progresses, so does the risk of chronic hyperkalemia to the point that more than 40% of patients on dialysis had a diagnosis of hyperkalemia in 2014.³

In most instances, hyperkalemia is asymptomatic and identified only after a serum level is drawn.¹ However, elevations in serum potassium may be associated with serious adverse events. As a result of hyperpolarization of cardiac tissue, cardiac complications may arise, ranging from small electrocardiogram (ECG) changes to bradycardia to sudden cardiac arrest.^1,2 Mild elevations in serum potassium (levels between 5.5 mEq and 6.5 mEq) are thought to produce fewer complications than severe elevations (levels above 8.0 mEq), though even mild elevations are associated with increased mortality risk or cardiac changes evident on an ECG.^2,6,7 Thus, it is important to recognize that although serum potassium levels may correlate with complications, they also may not, and clinicians should not ignore even slight elevations.

Other complications of hyperkalemia involve the skeletal muscle system, which may present as benignly as muscle weakness or fatigue or as seriously as temporary paralysis.⁸ Further, hyperkalemia is a common reason for patients with CKD to progress to dialysis.⁶ Individuals with hyperkalemia are not only at risk for these important complications. They also consume significantly more health care resources than those without hyperkalemia. For instance, patients with hyperkalemia were shown to incur health care costs more than $4,000 higher than similar patients without this diagnosis over a 30-day period, and almost $16,000 more over the course of a year.⁹ Individuals with stage 5 CKD and hyperkalemia incurred costs of almost $53,000 over 1 year as compared with those without hyperkalemia.⁹

Case 1: 79 yo female with stage 3 CKD, 24-year history of hypertension (HTN), and 19-year history of type 2 DM, and a 2-year history of osteoarthritis. She has had numerous bouts of hyperkalemia that have generally been mild. Current medications: losartan 25 mg once daily, hydrochlorothiazide 25 mg once daily, furosemide 80 mg once daily, and ibuprofen 200 mg, 1-2 tablets as needed for pain. What risk factors does this patient have for the continued development of hyperkalemia?

Causes of Hyperkalemia

Hyperkalemia can be caused by 1 of 3 mechanisms: increased potassium intake, impaired excretion, or impaired potassium balance within the extracellular fluid (ECF) and intracellular fluid (ICF). Table 1 lists risk factors.

Increased Potassium Intake

The first mechanism by which chronic hyperkalemia may be caused is excessive potassium intake. In otherwise healthy individuals, the body is able to cope with an unusually high potassium load through increased excretion via the kidneys. However, in those with underlying impaired renal function, as impairment worsens, so does the body's ability to maintain normal potassium homeostasis.⁸

The recommended daily potassium intake for most adults is 4,700 mg, though most individuals consume significantly less.¹¹ In patients with hypertension, however, greater potassium intake may be warranted, though specific recommendations are unclear regarding their ideal potassium intake. Data has shown increased potassium intake is linked to reduced stroke risk and may also be associated with lower cardiovascular mortality.^12,13 This may be related to increased sodium excretion in the urine.¹⁴ Interestingly, in those with HTN in the early stages of CKD, high potassium intake may also have renoprotective effects, slowing the progression of the disease.¹⁵ However, data is limited at this time, so the potential benefits of increasing potassium intake must be weighed against the risk of hyperkalemia.

The majority of potassium intake comes from 3 notable sources: diet, supplements, and salt substitutes. Table 2 lists foods containing high levels of potassium. Apricots, lentils, and prunes have some of the highest quantities of potassium per serving, while milk, coffee, and potatoes are major sources of potassium in American diets.¹¹ Supplements typically make up only a minor portion of potassium intake, as FDA limits doses in over-the-counter supplements to a maximum of less than 100 mg.¹¹ Finally, salt substitutes typically contain potassium chloride and may be quite potent (up to 2,800 mg of potassium per tablespoon).¹¹ Balancing potassium intake with medications that increase serum levels or limit potassium excretion is an important consideration when treating patients with any stage of CKD.

Impaired Excretion

As previously stated, 90% of the body's potassium is excreted through the kidneys. Any impairment in normal renal function can reduce elimination and increase serum potassium levels. While the body attempts to compensate for impaired renal excretion by increasing aldosterone secretion and excreting additional potassium through the gastrointestinal tract, these compensatory mechanisms are often insufficient to maintain a normal serum potassium concentration.¹ It is no surprise then, that impaired renal function is the primary driver of hyperkalemia.⁶

Chronic kidney disease is the most common reason for impaired renal excretion of potassium.¹⁶ As CKD progresses, functionality of the distal nephron continuously declines, reducing the kidneys' ability to effectively eliminate potassium.⁷ Typically, hyperkalemia arises in the latest stages of the disease, but may present sooner if patients have additional risk factors, such as male sex, increased age, comorbidities, and medications, including RAAS inhibitors, mineralocorticoid receptor antagonists, and beta blockers.^7,8,16

Other medical conditions, such as DM and CHF, may worsen hyperkalemia in the presence of CKD, but may also be independent risk factors for developing hyperkalemia.⁷ Diabetes mellitus is associated with hyporeninemic hypoaldosteronism, a complication that reduces serum aldosterone levels due to dysfunctional RAAS.¹⁷ CHF is also associated with impaired renal excretion due to reduced renal perfusion and subsequent kidney injury.⁸ Additionally, patients with CHF also experience high levels of aldosterone, which counterintuitively causes more sodium absorption earlier within the nephron. In turn, less sodium is passively reabsorbed in the distal nephron, leading to decreased potassium excretion.⁵

The relationship between CKD, CHF, and DM with hyperkalemia is convoluted by the fact that these conditions often coexist.⁸ Further complicating things, common medications are used to treat these conditions and may independently impact serum potassium concentrations.

One of the classes of medications used most frequently for these conditions are RAAS inhibitors, including angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor antagonists or "blockers" (ARBs), and the newest addition, the angiotensin receptor-neprilysin inhibitor (ARNI), valsartan/sacubitril. While medications within these classes have been shown to be effective for CKD, CHF, and DM and their use is supported in particular patient populations by current guidelines, they are also a known cause of hyperkalemia.^18-20 Though less frequently used, another RAAS inhibitor is the direct renin inhibitor, aliskiren. This drug is also associated with infrequent hyperkalemia.²¹

RAAS inhibitors can increase serum potassium levels by blocking angiotensin II's effects on the adrenal glands. This, in turn, reduces aldosterone secretion, which then decreases potassium excretion.²² These medications have been shown to cause hyperkalemia in about 10% of patients treated on an outpatient basis.²³ ARNIs have also been shown to increase serum potassium, though to a lesser extent than ACE inhibitors.^24,25 Appropriate monitoring for all of these agents may help prevent hyperkalemia. However, evidence-based monitoring timelines have yet to be developed and patient and provider adherence is lacking to consensus-based recommendations.²²

In addition, mineralocorticoid receptor antagonists are commonly used in heart failure, and have been shown to more than double the risk of hyperkalemia.^20,26 Drugs within this class work in 1 of 2 of ways – either through antagonism of aldosterone receptors (eplerenone, spironolactone) or through blockade of sodium reabsorption within the collecting duct (amiloride, triamterene).²² Both mechanisms lead to reduced renal excretion of potassium.

One additional medication class that affects potassium excretion, the non-steroidal anti-inflammatory drugs (NSAIDs), is worth noting. NSAIDs may cause or exacerbate hyperkalemia by several mechanisms. First, NSAIDs inhibit prostaglandins, which in turn inhibits release of renin. Through the RAAS, this reduces aldosterone release, and thus, potassium excretion.²⁷ Next, similar to what is seen in CHF, NSAIDs induce sodium reabsorption earlier within the nephron, which decreases the amount of sodium to be exchanged with potassium in the luminal channels of the distal nephron.²⁷ Finally, NSAIDs may also be associated hyporeninemic hypoaldosteronism.²⁷ NSAIDs are associated with severe renal adverse and cardiac events, so it is best to avoid these agents in individuals with CHF and/or CKD.^28,29

Extracellular/Intracellular Potassium Imbalance

Ninety-eight percent of the body's potassium is maintained in the ICF, while the remaining 2% resides in the ECF.² The body's primary mechanism for maintaining this balance is through the aforementioned Na+/K+ ATPase. This enzyme, located in the membrane of most cells, moves 3 sodium ions out of the cell and 2 potassium ions against their concentration gradient into the cell.^1,8 Defects in this enzyme increase serum potassium levels through impaired movement of potassium from the ECF to the ICF.²

Another situation in which the extracellular/intracellular potassium balance is not appropriately maintained is in metabolic acidosis. Potassium ions shifts to the ECF in exchange for hydrogen ions in an attempt to balance the body's pH.⁸ Also, in addition to the previously described means by which DM impacts serum potassium levels, insulin deficiency is also associated with movement of potassium from the ICF to the ECF.⁶ In the acute treatment of hyperkalemia insulin may be used to counter these effects.

Medications, including beta-blockers and digoxin, can also decrease potassium uptake into cells. Stimulation of beta-2 adrenergic receptors is partially responsible for movement of potassium from the ECF to the ICF.² Thus, inhibition of these receptors with use of beta-blockers, particularly those that exhibit non-selective receptor blockade, can raise serum potassium levels.^2,8 This is why beta agonists, such as albuterol, may be used in the acute treatment of hyperkalemia. Digoxin may also impact potassium transport through direct interference with the Na+/K+ ATPase. This dose-dependent interaction is often not clinically significant but may worsen existing hyperkalemia.⁸

Returning to Case 1: What risk factors does this patient have for the continued development of hyperkalemia? Since the patient has stage 3 CKD, her risk of developing hyperkalemia is increased compared to patients without. Further, DM may also increase the risk of hyperkalemia through various mechanisms. Additionally, the patient is currently treated with 2 medications that can increase her risk for hyperkalemia – an ARB (losartan) and an NSAID (ibuprofen). Next, it would be prudent to inquire about diet, as the patient's intake may need to be adjusted given her comorbidities. Finally, given her lengthy history of HTN, it is plausible she is using potassium-containing salt substitutes.

TREATMENT

Treatment for hyperkalemia should involve a multimodal approach, incorporating lifestyle changes, adjustments to modifiable risk factors, and pharmacologic intervention. It is important to note that hyperkalemia can either be an acute, life-threatening issue or a chronic concern. Clinicians manage these 2 presentations quite differently. The decision to implement outpatient management of hyperkalemia should be based on the severity of hyperkalemia. Patients with mild disease (serum potassium between 5.0 and 6.0 mEq/L) can generally be managed outpatient. Higher levels require additional cardiac assessment but may still be treated appropriately in an outpatient setting.³⁰

Lifestyle Changes

The first intervention to discuss with patients is dietary adjustment. Individuals at risk for hyperkalemia should closely monitor their potassium intake. Appropriate dietary modification can reduce the prevalence of hyperkalemia, decrease serum potassium fluctuations, and even resolve elevated potassium levels.³¹ Unfortunately, the relationship between high potassium intake and improved or worsened outcomes is still unclear and recommending limited potassium intake in all individuals may be premature.¹⁵ Additionally, in those for whom dietary reduction of potassium intake is appropriate, intervention may have limited efficacy due poor adherence.⁶

Adjustments to Modifiable Risk Factors

Various risk factors for hyperkalemia exist, including comorbidities and medications discussed previously. Many of these are modifiable and should be considered as potential targets for intervention. First, the primary driver for the severity of chronic hyperkalemia is the degree of impairment in renal function.³² Interventions to minimize CKD progression should be made, including maintaining blood pressure and glycemic control and the initiation of ACE inhibitor or ARB therapy in those with proteinuria.¹⁸

Next, clinicians should make an effort to limit patient exposure to unnecessary medications, both prescription and over-the-counter, that may increase risk of hyperkalemia. For instance, NSAIDs should be discontinued and alternative pain management modalities, such as acetaminophen, should be instituted.³² Patients should be maintained on therapies that have proven clinical advantage until the risk of continuation outweighs the potential benefits. RAAS inhibitors may be discontinued prematurely or inappropriately avoided on the basis of renal impairment, which may lead to worse cardiovascular and renal outcomes.³² Instead, high risk patients should undergo laboratory monitoring within 1 to 2 weeks of initiation and periodically thereafter to ensure serum potassium levels remain within normal limits.¹⁰

Finally, clinicians should minimize the risk of combining medications. To do so, providers should first avoid dual blockade of the RAAS in those who are already at an increased risk of hyperkalemia.²² Additionally, providers should recognize that combination therapy with mineralocorticoid receptor antagonists and RAAS inhibitors significantly increases the risk of hyperkalemia compared with either drug alone.³³ They should consider lower doses of each of these drugs when combining therapy, along with closer monitoring.²² Finally, in patients with CHF at risk for hyperkalemia, clinicians should consider ARNI therapy over ACE inhibitors, as valsartan/sacubitril was shown to have a lesser risk of hyperkalemia than enalapril.²⁵

Pharmacologic Intervention

Case 2: 57 yo male with NYHA class III systolic CHF and estimated glomerular filtration rate (eGFR) 62 mL/min/1.73 m2 treated with guideline-directed medical therapy, including an ACE inhibitor, beta-blocker, loop diuretic. His electrolytes are within normal limits. Spironolactone 25 mg is added to address ongoing CHF symptoms. One month later, his dyspnea has improved, but his potassium level is found to be 6.2 mEq/L. ECG is normal. He is experiencing nausea and generalized weakness. The provider determines, based on the patient's normal ECG, that he will be managed outpatient. How would you recommend this patient be treated?

Potassium-wasting diuretics, including loop and thiazide diuretics, work by inhibiting reabsorption of sodium early in the nephron. This delivers more sodium for exchange in the distal nephron, which leads to increased potassium excretion.¹⁰ Diuretics have been shown to decrease the incidence of hyperkalemia by nearly 60%, making them important medications to consider in patients at risk for developing hyperkalemia.³⁴ Either loop diuretics (e.g. furosemide, torsemide) or thiazide diuretics (e.g. hydrochlorothiazide, chlorthalidone) may be considered appropriate options in most patients, while loop diuretics are preferred in those with more advanced CKD (eGFR below 30 mL/min/m²).¹⁰ Caution must be exercised when prescribing diuretics to maintain normokalemia, however, as mortality related to potassium homeostasis follows a U-shaped curve. That is, the risk of death increases if potassium levels fall below 3.5 mEq/L or climb above 5.5 mEq/L.¹⁶ Additionally, diuretics have the potential to worsen renal function in the presence of hypovolemia.⁶ Careful monitoring of serum potassium and volume status is required.

Until recently, the use of medications to help maintain normokalemia other than diuretics has remained unchanged for decades.¹⁰ The recent availability of 2 new agents, patiromer and sodium zirconium cyclosilicate (SZC), has significantly improved the treatment of this condition. Prior to this, sodium polystyrene sulfonate (SPS) was the mainstay of potassium-removal therapy, though efficacy data to support its use are very limited.^35,36

Sodium polystyrene sulfonate

Sodium polystyrene sulfonate is available as a suspension for oral administration or in an enema and is dosed 4 times daily.³⁷ It is a cation exchange resin that works to remove potassium by exchanging sodium ions for potassium ions in the gastrointestinal tract.³⁷ Unfortunately, SPS is associated with serious complications, including intestinal necrosis, particularly when combined with sorbitol.³⁶ Additionally, in late 2017, FDA issued a warning to avoid co-administration of other oral medications within 3 hours of SPS because of its ability to reduce other medications' absorption and subsequent effectiveness.³⁸ Further, since sodium is exchanged for excreted potassium, patients with conditions that may be affected adversely by additional sodium absorption or increased fluid load, such as those with hypertension or CHF, respectively, should use SPS with caution.^37,39 Other common adverse events include anorexia, nausea, vomiting, and constipation.³⁷ Given its limited efficacy, its propensity to cause adverse events, and the availability of 2 new agents, the role of SPS has been significantly minimized.

Patiromer

In 2015, FDA approved patiromer (Veltassa) for the treatment of non-emergent hyperkalemia.⁴⁰ Patiromer is non-absorbable and exerts its effects by binding to potassium in the gastrointestinal tract to reduce absorption.⁴⁰ Patiromer begins working within 7 hours, peaks within 48 hours, and maintains its effects for approximately 24 hours after the last dose is taken.⁴⁰ Patiromer has been shown to be effective in decreasing serum potassium and maintaining normokalemia in patients with a variety of background comorbidities and concomitant medications.

In the phase II AMETHYST-DN trial, patients treated with patiromer with diabetic kidney disease on RAAS inhibitor therapy successfully had their serum potassium levels lowered between 0.35 mEq/L and 0.97 mEq/L, depending on their assigned dose. Effects were seen at 4 weeks and were maintained through 52 weeks.⁴¹ Another phase II trial, PEARL-HF, examined patiromer's effects on normokalemic CHF patients starting spironolactone. These patients also had either CKD and were on at least 1 CHF medication (ACE inhibitor, ARB, or beta-blocker), or had a history of hyperkalemia leading to discontinuation of a RAAS inhibitor, aldosterone antagonist, or beta-blocker within the preceding 6 months. At 4 weeks, patiromer was associated with significantly lower serum potassium levels (difference of -0.45 mEq/L compared with placebo), allowed for higher spironolactone doses (91% versus 74% of patiromer-treated patients and placebo-treated patients, respectively, were able to increase their dose to 50 mg per day), and reduced the incidence of hyperkalemia compared with placebo.⁴²

One phase III trial, OPAL-HK, was also completed.⁴³ Patiromer was shown to reduce serum potassium levels in patients with hyperkalemia and CKD currently treated with RAAS inhibitors by 1.01 mEq/L. Through 8 weeks, patiromer-treated patients experienced a 75% risk reduction in the development of hyperkalemia compared with placebo-treated patients.⁴³ Several post-hoc analyses were also completed. Patiromer was shown to reduce serum aldosterone levels, blood pressure, and urinary albumin excretion.⁴⁴ It has also been shown to have consistent effects regardless of background diuretic therapy and in patients 65 years of age and older.^45,46

Patiromer is available as a powder for oral suspension, to be mixed with one-third cup of water immediately prior to administration.⁴⁰ The dose should initiated at 8.4 g once daily, then, based on current and target serum potassium levels, the dose should be titrated in increments of 8.4 g no more frequently than every 1 week up to a maximum of 25.2 g once daily.⁴⁰ Though it is well tolerated overall, it may worsen preexisting gastrointestinal conditions like severe constipation or bowel obstruction and should be avoided in these patients.^39,40 Patients should be monitored for hypomagnesemia, as this was seen in more than 5% of patients in clinical trials, though no adverse sequelae were observed as a result.^40,47 Other adverse events were limited to gastrointestinal complications, including constipation, diarrhea, nausea, and abdominal discomfort.

Sodium Zirconium Cyclosilicate

The newest agent to market for hyperkalemia is sodium zirconium cyclosilicate, which FDA approved in May 2018 under the brand name Lokelma.⁴⁸ Similar to patiromer, SZC is a non-absorbable potassium binding agent that targets potassium in the gastrointestinal tract.⁴⁸

Two phase III trials were completed to determine SZC's safety and efficacy. The HARMONIZE trial compared the change in serum potassium between several doses of SZC to placebo in patients with hyperkalemia.⁴⁹ After a 48-hour open-label run-in period, patients achieving normokalemia received 1 of 3 doses of SZC (5 g, 10 g, or 15 g) once daily or placebo for 28 days. In the open-label period, serum potassium levels decreased 1.1 mEq/L at 48 hours with 98% of patients achieving normokalemia. At 28 days, serum potassium was statistically significantly lower and significantly more patients achieved normokalemia in each of the 3 SZC groups compared with placebo.⁴⁹ Importantly, at doses of 10 g and 15 g daily, SZC significantly reduced serum potassium levels across all subgroups, including those with CKD, DM, CHF, and those on RAAS inhibitors. The difference was not significant for patients with DM or those taking RAAS inhibitors on the 5 g dose.⁴⁹

The second phase III trial completed investigated the rate of change in serum potassium secondary to various doses of SZC compared with placebo using a similar design to the HARMONIZE trial.⁵⁰ During the 48-hour open-label run-in period, serum potassium levels decreased at a significantly faster rate compared with placebo in those treated with 2.5 g, 5 g, and 10 g of SZC. These results were seen regardless of baseline renal function, potassium level, use of RAAS inhibitors, or comorbid conditions (DM, CKD, or CHF). At the end of the second stage, the 14-day maintenance period, the 5 g and 10 g doses were more effective than placebo at maintaining normokalemia. Hyperkalemia recurred 1 week after discontinuation of the 10 g dose.⁵⁰

While FDA placed a Limitation of Use note in SZC's labeling that it should not be used for emergency treatment of life-threatening hyperkalemia, it is reported to exert its effects more quickly than patiromer.⁴⁸ Specifically, while patiromer begins working within 7 hours, SZC was shown to lower serum potassium levels by 0.4 mEq/L in slightly over 1 hour, and by 0.7 mEq/L at 4 hours.⁵¹

Sodium zirconium cyclosilicate is available in 5 g or 10 g powder packets and is dosed 10 g 3 times daily initially, then reduced to 10 g once daily after 48 hours. The dose may then be adjusted based on serum potassium levels in intervals of at least one week, with the maintenance dose falling between 5 g every other day to 15 g daily.⁴⁸ Other medications should be administered 2 hours before or after administration of SZC.⁴⁸ Though SZC was well-tolerated in clinical trials, similarly to patiromer, SZC may worsen preexisting gastrointestinal issues and should be avoided in patients with severe constipation or other motility disorders.⁴⁸ It should be used with caution in patients at risk for edema due to the 400 mg sodium contained in each 5 g dose.⁴⁸

Returning to Case 2: The provider determines, based on the patient's normal ECG, that he will be managed in an outpatient setting. How would you recommend this patient be treated? Initial treatment should consist of nonpharmacologic treatment interventions, including dietary counseling (decreased potassium intake, counseling on potassium-rich foods, and avoidance or limitation of salt substitutes) and reduction of risk factors (avoidable medications, controlling comorbidities). Unfortunately, in this case, the addition of a medication intended to control the patient's underlying CHF better appears to be causing the hyperkalemia. Consider the addition of patiromer as it may maintain normokalemia and allow higher doses of the spironolactone, if necessary. Sodium zirconium cyclosilicate is another potential option but contains 400 mg sodium in every 5 g dose, which may cause problematic edema in a patient with CHF.

The approval of patiromer and SZC provides effective new tools to combat chronic hyperkalemia. Perhaps the most important role of these products, however, is their ability to prevent premature discontinuation of medications shown to improve outcomes in common comorbidities, including the RAAS inhibitors and aldosterone antagonists. This provides the opportunity to maintain therapy with these valuable medications, while shedding some concern about a hyperkalemia, a side effect that once frequently precluded their use.

CONCLUSION

Hyperkalemia may represent an acute, life-threatening issue, but increases in serum potassium on a chronic basis also confer negative outcomes for patients and society. Understanding which medications and conditions increase the chances of hyperkalemia can help pharmacists identify at risk patients. Further, chronic hyperkalemia is now a very treatable condition with the availability of patiromer and SZC. These effective, well-tolerated medications have changed the landscape of treatment for this condition. Appreciating the evidence and safety considerations for these products allows clinicians to individualize care to achieve the best outcomes for every patient.

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