How to manage hyperkalemia in patients with Chronic Kidney Disease (CKD)?

Management of Hyperkalemia in Chronic Kidney Disease

For CKD patients with hyperkalemia, use the newer potassium binders patiromer or sodium zirconium cyclosilicate (SZC) as first-line therapy to effectively lower potassium while maintaining cardioprotective RAAS inhibitor therapy, rather than discontinuing these life-saving medications. 1, 2

Severity-Based Treatment Algorithm

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

• Start patiromer 8.4g once daily OR SZC 5g once daily 2
• Continue RAAS inhibitors at current dose 1, 2
• Monitor serum potassium within 1 week of starting therapy 1
• If not on maximum guideline-recommended RAAS inhibitor dose, consider up-titration with close potassium monitoring 1

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

• Initiate patiromer 8.4g once daily OR SZC 10g once daily 2
• Consider temporary reduction (not discontinuation) of RAAS inhibitor dose 2
• Recheck potassium within 3-7 days 1
• Once potassium <5.0 mEq/L, resume full RAAS inhibitor dosing 1

Severe Hyperkalemia (K+ >6.0 mEq/L)

• Refer to emergency department for acute management if K+ >6.5 mEq/L 1, 2
• Temporarily discontinue RAAS inhibitors until K+ <5.0 mEq/L 1, 2
• Start potassium binder therapy once acute management complete 2
• For acute correction with SZC: 10g three times daily for 48 hours, then 5-10g daily for maintenance 2, 3
• Reintroduce RAAS inhibitors one at a time with close monitoring once potassium controlled 1

Potassium Binder Selection and Characteristics

Sodium Zirconium Cyclosilicate (SZC)

• Fastest onset of action at 1 hour 1, 2
• Highly selective for potassium (also binds NH4+) 1
• Works in both small and large intestines 1
• Mean serum K+ reduction of 1.1 mEq/L over 48 hours 2
• Contains 400mg sodium per 5g dose 1
• Dosing: 10g TID for 48 hours (acute), then 5g every other day to 15g daily (maintenance) 1

Patiromer

• Onset of action approximately 7 hours 1, 2, 3
• Binds potassium in exchange for calcium in the colon 1, 3
• Mean serum K+ reduction of 1.01 mEq/L at 4 weeks in CKD patients on RAAS inhibitors 2, 3
• Sodium-free formulation (advantageous in CKD) 2
• Contains 1.6g calcium per 8.4g dose 1
• Must be separated from other oral medications by 3 hours (6 hours if gastroparesis) 2, 3
• Dosing: 8.4g once daily, titrate up to 16.8g or 25.2g daily as needed 1, 3

Sodium Polystyrene Sulfonate (SPS/Kayexalate)

• Avoid when possible due to serious gastrointestinal adverse events including intestinal necrosis 1, 2, 4
• Variable onset of action (several hours to days) 1, 4
• High sodium content (1500mg per 15g dose) 1
• Never use with sorbitol due to increased risk of intestinal necrosis 2
• Nonselective binding causes hypocalcemia and hypomagnesemia 1, 4
• Overall mortality rate of 33% in patients experiencing GI complications 2

Dietary Management

Potassium Restriction Approach

• Limit intake of foods rich in bioavailable potassium (especially processed foods) for CKD G3-G5 patients with history of hyperkalemia 1
• Target <2000-3000mg (50-75 mmol) potassium daily for adults 1
• Equivalent to <30-40 mg/kg/day (0.8-1 mmol/kg/day) 1
• Avoid potassium-containing salt substitutes which can cause life-threatening hyperkalemia 1

Practical Dietary Strategies

• Restrict high-potassium foods: bananas, oranges, potatoes, tomato products, legumes, yogurt, chocolate 1
• Presoaking root vegetables (including potatoes) lowers potassium content by 50-75% 1
• Foods with <100mg or <3% daily value are low in potassium 1
• Foods with >200-250mg or >6% daily value are high in potassium 1
• Dietary counseling through renal dietitian is advised 1

RAAS Inhibitor Management Strategy

Key Principle

Do NOT discontinue RAAS inhibitors as first-line approach for mild-to-moderate hyperkalemia, as these medications provide critical cardiorenal benefits 2

Monitoring Protocol

• Check serum potassium and GFR within 1 week of starting RAAS inhibitor or any dose escalation 1
• Monitor potassium at 3 days, 1 week, and monthly for first 3 months when on potassium binders 2
• Recheck within 1-2 weeks of any medication change 2

Reinitiation After Hyperkalemia

• Restart RAAS inhibitors once concurrent conditions contributing to hyperkalemia are controlled AND serum K+ <5.0 mEq/L 1
• Reintroduce agents one at a time with monitoring of kidney function and electrolytes 1
• For moderate/severe hyperkalemia, wait until K+ within patient's usual range (whichever is higher between <5.0 mEq/L or usual range) 1

Additional Contributing Factors to Address

Medications to Review

• Potassium-sparing diuretics 1
• Direct renin inhibitors, verapamil, mannitol 1
• Herbal products: potassium supplements, alfalfa, dandelion, horsetail, Lily of the Valley, milkweed, nettle 1

Clinical Conditions

• Metabolic acidosis 1
• Constipation 1
• Urinary obstruction 1
• Rhabdomyolysis, hemolysis, tumor lysis 1

Adjunctive Strategies

• SGLT2 inhibitors may reduce hyperkalemia risk (HR 0.84; 95% CI 0.76-0.93) 2
• Optimize diuretic therapy (effectiveness depends on residual kidney function) 2
• Address hypertension and hypervolemia 1

Critical Pitfalls to Avoid

• Never discontinue RAAS inhibitors without attempting potassium binder therapy first - mortality rates are highest among patients who discontinue RAASi therapy 2, 5
• Avoid triple combination of ACE inhibitor + ARB + aldosterone antagonist due to significantly increased hyperkalemia risk 2
• Do not use sodium polystyrene sulfonate when newer agents are available due to serious GI adverse events 2
• Do not rely solely on dietary potassium restriction as this deprives patients of beneficial potassium-rich foods 2
• Remember to separate patiromer from other oral medications by 3 hours to avoid drug interactions 2, 3
• Do not initiate RAAS inhibitors if K+ >5.0 mEq/L per NICE guidelines 1

Laboratory Monitoring Considerations

• Be aware of variability in potassium measurements including diurnal and seasonal variation, plasma versus serum samples 1
• Renal potassium excretion typically maintained until GFR <10-15 mL/min/1.73 m² 1
• Rule out spurious values and hemolysis before treatment escalation 1