What are the first‑line agents to increase potassium excretion in a patient with hyperkalemia?

First-Line Agents to Increase Potassium Excretion in Hyperkalemia

The first-line agents to increase potassium excretion in patients with hyperkalemia are loop diuretics (such as furosemide 40-80 mg daily) for those with adequate renal function, and the newer potassium binders—sodium zirconium cyclosilicate (Lokelma) or patiromer (Veltassa)—for chronic management, particularly in patients requiring continuation of RAAS inhibitor therapy. 1, 2, 3

Acute Potassium Excretion: Loop Diuretics

For patients with adequate kidney function (eGFR >30 mL/min) and sufficient urine output, loop diuretics such as furosemide 40-80 mg IV or oral are the primary agents to increase renal potassium excretion. 1, 3 These agents work by stimulating flow and sodium delivery to the renal collecting ducts, which enhances potassium secretion. 3 However, diuretics should be titrated to maintain euvolemia rather than used primarily for potassium management alone. 3

A critical caveat: Loop diuretics are ineffective in patients with severe renal impairment (eGFR <30 mL/min), oliguria, or anuria—in these cases, hemodialysis becomes the definitive method for potassium removal. 3

Chronic Potassium Excretion: Newer Potassium Binders

Sodium Zirconium Cyclosilicate (Lokelma)

Lokelma is the preferred first-line potassium binder when faster onset is needed, with action beginning within 1 hour. 2, 3 The dosing regimen is:

• Acute correction phase: 10 g three times daily for 48 hours 2, 3, 4
• Maintenance phase: 5-15 g once daily 2, 3

Lokelma achieves a mean potassium reduction of approximately 1.1 mEq/L over 48 hours. 2, 5 It works by binding potassium in exchange for hydrogen and sodium throughout the small and large intestines, with high selectivity for potassium. 1, 4

Important safety considerations:

• Each 10 g dose contains 1200 mg sodium during correction phase and 400-1200 mg sodium daily during maintenance, which may cause dose-dependent edema (2% at 5 g, 6% at 10 g, 14% at 15 g daily). 2, 5
• Monitor for peripheral edema and adjust in patients with heart failure or volume overload. 3, 5
• Most common adverse effects are gastrointestinal (constipation, diarrhea, nausea). 2, 5

Patiromer (Veltassa)

Patiromer is an effective alternative with slower onset (~7 hours) but excellent long-term safety profile. 1, 2 The dosing regimen is:

• Starting dose: 8.4 g once daily with food 2, 3
• Titration: Up to 16.8 g or 25.2 g daily based on potassium response 2, 3

Patiromer binds potassium in exchange for calcium in the colon, increasing fecal excretion. 1, 6 It must be separated from other oral medications by at least 3 hours to avoid reduced absorption. 2, 3

Important safety considerations:

• Monitor magnesium levels, as patiromer can cause hypomagnesemia. 2, 3
• May cause hypercalcemia due to calcium exchange. 3
• Each 8.4 g dose contains 4000 mg sorbitol. 1

Critical Clinical Algorithm

For Acute Hyperkalemia (K+ >6.0 mEq/L):

1. If adequate renal function (eGFR >30 mL/min): Initiate loop diuretics (furosemide 40-80 mg IV) 3
2. If severe renal impairment or oliguria: Hemodialysis is the most effective method 3
3. Concurrent measures: Insulin/glucose, beta-agonists, and calcium (if ECG changes) for intracellular shift while awaiting excretion 3

For Chronic Hyperkalemia (K+ 5.0-6.5 mEq/L):

1. If patient requires RAAS inhibitor continuation: Initiate Lokelma (faster onset) or patiromer (slower onset but excellent safety) 2, 3
2. Optimize diuretic therapy if not already on adequate doses 3
3. Address metabolic acidosis with sodium bicarbonate if present (pH <7.35, bicarbonate <22 mEq/L), as this promotes potassium excretion through increased distal sodium delivery 1, 3

Enabling RAAS Inhibitor Therapy: A Major Benefit

A critical advantage of the newer potassium binders is enabling continuation and optimization of RAAS inhibitors in patients who would otherwise require dose reduction or discontinuation. 2 Discontinuation of RAAS inhibitors leads to adverse cardiorenal outcomes, and both patiromer and Lokelma allow higher proportions of patients to maintain or increase RAAS inhibitor doses. 2 In the PEARL-HF trial, patiromer enabled 86% of heart failure patients to remain on spironolactone 50 mg daily versus 66% with placebo. 2

Agents to Avoid

Sodium polystyrene sulfonate (Kayexalate) should be avoided as a first-line agent due to serious safety concerns. 2, 3 It is associated with intestinal ischemia, colonic necrosis, and a doubling in risk of hospitalization for serious GI adverse events. 2 Additionally, it has variable and delayed onset of action, and causes hypocalcemia and hypomagnesemia. 2 The American College of Physicians recommends against its use due to limited efficacy and safety concerns. 2

Monitoring Protocol

Check potassium within 1 week of starting or escalating any potassium excretion therapy. 3 For patients on RAAS inhibitors, reassess potassium 7-10 days after dose changes. 3 Individualize monitoring frequency based on comorbidities (CKD, diabetes, heart failure) and history of hyperkalemia. 3 Regular monitoring is essential to avoid overcorrection and hypokalemia, particularly in hemodialysis patients. 2

Common Pitfalls to Avoid

• Do not use loop diuretics in patients with severe renal impairment (eGFR <30 mL/min)—they will be ineffective. 3
• Do not use sodium bicarbonate without documented metabolic acidosis—it is ineffective without acidosis. 3
• Do not permanently discontinue RAAS inhibitors due to hyperkalemia—use potassium binders to maintain these life-saving medications. 2, 3
• Remember that calcium, insulin, and beta-agonists do not remove potassium from the body—they only temporize while awaiting definitive excretion. 3