How to manage persistent hyperkalemia in a patient undergoing peritoneal dialysis (PD)?

Management of Persistent Hyperkalemia in Peritoneal Dialysis Patients

For PD patients with persistent hyperkalemia despite adequate dialysis, initiate sodium zirconium cyclosilicate (SZC) 10g three times daily for 48 hours, then 5-15g once daily for maintenance, while simultaneously investigating and addressing reversible causes including dietary indiscretion, inadequate dialysis prescription, medication contributors, and metabolic acidosis. 1, 2

Initial Assessment: Rule Out Reversible Causes

Before escalating treatment, systematically evaluate the following:

Verify Adequate Dialysis Prescription

• Review peritoneal equilibration test (PET) status and adjust dwell times accordingly - high transporters may have inadequate potassium removal with long dwells 3
• Measure 24-hour dialysate effluent volume and calculate peritoneal potassium clearance 3
• Consider switching from CAPD to APD or vice versa to optimize clearance 3
• Evaluate for peritoneal membrane failure if previously well-controlled patients develop new hyperkalemia 4

Assess Residual Kidney Function (RKF)

• Loss of RKF is a critical contributor to hyperkalemia in PD patients - measure 24-hour urine volume and creatinine clearance 3, 4
• In patients with preserved RKF, consider high-dose loop diuretics (furosemide 80-160mg daily) to enhance urinary potassium excretion 3
• ACE inhibitors and ARBs help preserve RKF in PD patients - do not discontinue these medications without first attempting potassium binders 3

Identify Medication Contributors

• Systematically review and eliminate or reduce contributing medications: 1
  • RAAS inhibitors (ACE inhibitors, ARBs, mineralocorticoid antagonists) - temporarily reduce dose if K+ >6.5 mEq/L 1
  • NSAIDs - discontinue if possible 1, 5
  • Potassium-sparing diuretics (spironolactone, amiloride, triamterene) 1
  • Beta-blockers 1
  • Trimethoprim, heparin 1
  • Potassium supplements and salt substitutes 1

Critical caveat: Do not permanently discontinue RAAS inhibitors in patients with cardiovascular disease or proteinuric kidney disease, as these provide mortality benefit - instead, use potassium binders to enable continuation 1

Evaluate for Metabolic Acidosis

• Check serum bicarbonate - if <22 mEq/L, acidosis is contributing to transcellular potassium shift 4, 6
• Optimize dialysate bicarbonate concentration (typically 35-40 mEq/L) 4
• Consider oral sodium bicarbonate supplementation if acidosis persists despite adequate dialysis 6

Dietary Assessment

• Obtain detailed dietary history focusing on high-potassium foods: bananas, oranges, potatoes, tomato products, legumes, chocolate 3
• Refer to dietitian for education on potassium restriction (target <2000-3000mg daily for adults) 3
• Important nuance: Hyperkalemia in PD patients is 3 times more common than hypokalemia, contrary to traditional teaching 4
• Evaluate for dietary non-compliance, particularly in patients with previously stable potassium levels 4, 5

Definitive Treatment: Potassium Binders

First-Line Agent: Sodium Zirconium Cyclosilicate (SZC/Lokelma)

SZC is the preferred potassium binder for PD patients due to rapid onset (1 hour) and proven efficacy in dialysis populations. 1, 2

Dosing Protocol:

• Acute phase: 10g three times daily with meals for 48 hours 2
• Maintenance phase: Start 5-10g once daily, titrate weekly in 5g increments based on potassium levels 2
• Maintenance dose range: 5g every other day to 15g daily 2
• Target potassium: 4.0-5.0 mEq/L 1, 2

Evidence Base:

• In Study 2,92% of hyperkalemic patients (baseline K+ 5.6 mEq/L) achieved normokalemia within 48 hours with SZC 10g TID 2
• Mean potassium decreased from 5.6 to 4.5 mEq/L during acute treatment 2
• Maintenance therapy with 5-15g daily maintained potassium in normal range (80-94% of patients vs 46% with placebo) 2
• In hemodialysis patients with persistent hyperkalemia, 41% achieved target potassium with SZC vs 1% with placebo - this demonstrates efficacy even in dialysis-dependent populations 2

Administration:

• Mix entire packet contents in 3 tablespoons of water, stir well, drink immediately 2
• Separate from other oral medications by at least 2 hours 2
• Can be taken with or without food 2

Second-Line Agent: Patiromer (Veltassa)

Use patiromer if SZC is unavailable or not tolerated, starting at 8.4g once daily with food. 1

Key Differences from SZC:

• Slower onset of action (~7 hours vs 1 hour) 1
• Must be taken with food 1
• Requires 3-hour separation from other medications (vs 2 hours for SZC) 1
• Can cause hypomagnesemia - monitor magnesium levels 1
• Exchanges calcium for potassium (vs sodium for potassium with SZC) 1

Special Considerations for PD Patients

Anuric vs Non-Anuric Patients

• Anuric PD patients have significantly higher risk of hyperkalemia (50.7% vs lower rates in non-anuric patients) 5
• Non-anuric patients may benefit from loop diuretics to enhance urinary potassium excretion 5
• Omeprazole use is associated with hypokalemia in non-anuric PD patients - consider discontinuing if hypokalemia develops 5

Dialysis Prescription Optimization

• For high transporters: Shorten long dwells (nocturnal dwell in CAPD, day dwell in APD) to prevent net fluid reabsorption and inadequate potassium clearance 3
• For low transporters: May tolerate longer dwells but ensure adequate exchange volume 3
• Consider icodextrin for long dwells to optimize ultrafiltration without compromising potassium removal 3
• Switch to APD if CAPD is inadequate - more frequent exchanges may improve potassium clearance 3

Monitoring Protocol

• Check potassium weekly during dose titration of potassium binders 1
• Once stable, monitor monthly along with routine PD adequacy assessment 3
• Monitor for hypokalemia - PD patients can develop hypokalemia with aggressive treatment, which may be more dangerous than mild hyperkalemia 3, 1
• Assess serum bicarbonate, albumin, and creatinine monthly to identify contributing factors 4, 5

Common Pitfalls to Avoid

• Do not discontinue RAAS inhibitors permanently - these medications provide mortality benefit in cardiovascular disease and slow CKD progression; use potassium binders instead 1
• Do not use sodium polystyrene sulfonate (Kayexalate) - ineffective for acute hyperkalemia and associated with bowel necrosis 1, 7
• Do not rely solely on dietary restriction - while important, dietary modification alone is usually insufficient in PD patients with persistent hyperkalemia 3, 4
• Do not overlook metabolic acidosis - this causes transcellular potassium shift and must be corrected 4, 6
• Do not assume adequate dialysis without measuring clearances - calculate peritoneal and renal potassium clearance to verify adequacy 3

When to Consider Transition to Hemodialysis

Consider switching to hemodialysis if: 7

• Hyperkalemia persists despite maximum-dose potassium binders (SZC 15g daily or patiromer 25.2g daily) 1, 2
• Recurrent life-threatening hyperkalemia (K+ >6.5 mEq/L with ECG changes) 1, 7
• Loss of peritoneal membrane function with inadequate clearance 4
• Patient unable to comply with dietary restrictions or medication regimen 4

Hemodialysis is the most effective method for potassium removal in severe, refractory cases - it can rapidly lower potassium by 1-1.5 mEq/L per session 1, 7, 6