What is the management of hyperkalemia in patients with Chronic Kidney Disease (CKD)?

Management of Hyperkalemia in CKD

Immediate Treatment Approach

For patients with CKD and hyperkalemia, prioritize newer potassium binders (patiromer or sodium zirconium cyclosilicate) over sodium polystyrene sulfonate to allow continuation of life-saving RAAS inhibitor therapy while effectively managing potassium levels. 1, 2

Severity-Based Treatment Algorithm

Mild Hyperkalemia (K+ 5.0-5.5 mEq/L):

• Start patiromer 8.4g once daily OR sodium zirconium cyclosilicate (SZC) 5g once daily 2
• Continue RAAS inhibitors at current dose 1, 2
• Check potassium and renal function within 1 week 1
• Implement dietary potassium restriction targeting <2,000-3,000 mg daily (approximately 30-40 mg/kg/d) 1

Moderate Hyperkalemia (K+ 5.5-6.0 mEq/L):

• Initiate patiromer 8.4g once daily OR SZC 10g once daily 2
• Consider temporary RAAS inhibitor dose reduction by 50% 1
• Recheck potassium within 3-7 days 1, 2
• Avoid high-potassium foods: bananas, oranges, potatoes, tomato products, legumes, yogurt, chocolate 1

Severe Hyperkalemia (K+ >6.0 mEq/L):

• Refer to emergency department for acute management with IV calcium gluconate, insulin/glucose, and beta-agonists 1, 2
• Temporarily discontinue RAAS inhibitors until K+ <5.0 mEq/L 1
• Start SZC 10g three times daily for 48 hours, then 5-10g daily for maintenance 1, 3
• Monitor potassium every 2-4 hours during acute phase 2

Pharmacologic Management

Preferred Potassium Binders

Sodium Zirconium Cyclosilicate (SZC/Lokelma):

• Mechanism: Highly selective K+ binding in exchange for H+ and Na+ throughout the GI tract 1
• Onset of action: 1 hour (fastest available) 1
• Dosing: 10g TID for 48 hours (acute), then 5-15g once daily (maintenance) 1, 3
• Mean K+ reduction: 1.1 mEq/L over 48 hours 2
• Contains 400mg sodium per 5g dose—monitor for edema in heart failure patients 3

Patiromer (Veltassa):

• Mechanism: Binds K+ in exchange for Ca2+ in the colon 1, 4
• Onset of action: 7 hours 1
• Dosing: 8.4g once daily, titrate up to 25.2g daily as needed 1, 4
• Mean K+ reduction: 1.01 mEq/L at 4 weeks 2
• Critical: Separate from other oral medications by 3 hours (6 hours if gastroparesis) 1, 4

Sodium Polystyrene Sulfonate (SPS/Kayexalate)—Avoid:

• Associated with intestinal necrosis, colonic ischemia, and 33% mortality rate when complications occur 1, 2
• Inconsistent efficacy with variable onset (hours to days) 1
• Nonselective binding causes hypocalcemia and hypomagnesemia 1
• Only use if newer agents unavailable due to formulary restrictions 1

Dietary Management

Implement strict potassium restriction through renal dietitian:

• Target <2,000-3,000 mg (50-75 mmol) daily for adults 1
• Avoid processed foods with high bioavailable potassium 1, 2
• Never use salt substitutes—they contain potassium chloride and cause life-threatening hyperkalemia 1
• Pre-soaking root vegetables (including potatoes) reduces potassium by 50-75% 1
• Foods <100mg or <3% DV are low potassium; >200-250mg or >6% DV are high potassium 1

RAAS Inhibitor Optimization

The goal is maintaining cardioprotective and renoprotective RAAS inhibitor therapy, not discontinuing it:

• 86% of patients on patiromer remained on spironolactone vs 66% on placebo 1
• Mortality rates are highest among patients who discontinue RAAS inhibitors 5
• Suboptimal RAAS inhibitor dosing increases mortality compared to full dosing 5
• Use potassium binders to enable continuation of RAAS inhibitors rather than stopping these life-saving medications 1, 2

Monitoring Protocol

Initial Phase (First Week):

• Check K+ and creatinine within 1 week of starting potassium binder 1
• If on RAAS inhibitors: recheck at 3 days and 7 days 1

Titration Phase:

• Weekly monitoring during dose adjustments 2
• Target K+ range: 4.0-5.0 mEq/L 1, 2

Maintenance Phase:

• Check at 1-2 weeks after stable dose achieved 2
• Then at 3 months 1, 2
• Subsequently every 6 months 1, 2

Adjunctive Strategies

Address Contributing Factors:

• Correct metabolic acidosis (increases K+ release from cells) 1, 6
• Treat constipation (increases colonic K+ losses when resolved) 1
• Consider SGLT2 inhibitors—reduce hyperkalemia risk (HR 0.84; 95% CI 0.76-0.93) 1, 2
• Use loop diuretics if residual kidney function present (GFR >10-15 mL/min/1.73m²) 1

Medication Review:

• Stop herbal supplements that raise K+: alfalfa, dandelion, horsetail, nettle 1
• Avoid NSAIDs—worsen renal function and increase hyperkalemia risk 1
• Monitor closely if on verapamil, mannitol, or direct renin inhibitors 1

Critical Pitfalls to Avoid

Never discontinue RAAS inhibitors as first-line approach for mild-to-moderate hyperkalemia—these medications provide critical cardiorenal benefits that outweigh hyperkalemia risk when managed with potassium binders 1, 2

Avoid sodium polystyrene sulfonate when possible due to serious gastrointestinal adverse events including intestinal necrosis 1, 2

Do not rely solely on dietary restriction—this deprives patients of heart-healthy potassium-rich foods (fruits, vegetables) without addressing the underlying problem 1, 7

Never combine potassium-sparing diuretics with potassium supplements in CKD patients—this dramatically increases hyperkalemia risk 1

Renal potassium excretion typically maintained until GFR <10-15 mL/min/1.73m²—earlier hyperkalemia suggests medication effect or other contributing factors 1