Hyperkalaemia in Chronic Kidney Disease

Hyperkalaemia in chronic kidney disease is serum potassium above 5.5 mmol/L, classed as mild (5.5 to 5.9), moderate (6.0 to 6.4) and severe (6.5 or more). It affects up to 40% of patients with stage G4 to G5 disease and arises when potassium intake and release exceed renal and colonic excretion.

Chronic kidney disease reduces distal flow and aldosterone dependent secretion, while renin-angiotensin-aldosterone system inhibitors, mineralocorticoid antagonists, NSAIDs, trimethoprim, heparin and calcineurin inhibitors raise the risk. Hyperkalaemia is a leading reason for stopping renoprotective drugs and a recognised cause of sudden death on dialysis.

Causes and precipitants

• Acute kidney injury on chronic kidney disease, low urine volume, volume depletion.
• Drugs: ACE inhibitors, angiotensin receptor blockers, spironolactone, eplerenone, finerenone, amiloride, trimethoprim, NSAIDs, heparin, ciclosporin, tacrolimus, beta blockers, digoxin toxicity, potassium supplements and salt substitutes.
• Metabolic acidosis, insulin deficiency and hyperglycaemia, tissue breakdown (rhabdomyolysis, tumour lysis, haemolysis, gastrointestinal bleeding), constipation, type 4 renal tubular acidosis, high potassium diet, missed dialysis.

• Often asymptomatic; detected on routine blood tests.
• Muscle weakness, ascending flaccid paralysis, paraesthesia, palpitations, nausea, reduced reflexes.
• ECG sequence: peaked T waves, PR prolongation and P wave flattening, QRS widening, sine wave pattern, bradycardia, atrioventricular block, ventricular fibrillation or asystole. The ECG can be normal despite severe hyperkalaemia.

Red flags

• Potassium 6.5 mmol/L or more, or 6.0 mmol/L or more with ECG changes, acute kidney injury or rapid rise.
• Broad QRS, bradycardia, sine wave pattern, or neuromuscular weakness.
• Hyperkalaemia in an oliguric patient or with rhabdomyolysis, tumour lysis or ongoing tissue injury.

• Repeat potassium on a fresh sample taken without a tourniquet or clenched fist; whole blood gas potassium returns faster and avoids haemolysis. Pseudohyperkalaemia occurs with haemolysis, thrombocytosis (platelets above 1000 x 10⁹/L), leucocytosis, and delayed processing.
• 12-lead ECG and continuous monitoring if potassium is 6.0 mmol/L or more.
• Creatinine, urea, bicarbonate, glucose, calcium, magnesium, creatine kinase, blood gas, urine electrolytes; digoxin level if relevant.
• Medication review and dietary history; transtubular potassium gradient is of limited use in advanced chronic kidney disease.

Differential diagnosis (cause)

• Reduced excretion (kidney injury, hypoaldosteronism, drugs), shifts (acidosis, insulin deficiency, beta blockade, exercise, digoxin toxicity), release (rhabdomyolysis, haemolysis, tumour lysis), excess intake.

Emergency (potassium 6.5 mmol/L or more, or 6.0 mmol/L or more with ECG changes)

• Continuous ECG monitoring and intravenous access.
• Membrane protection: calcium gluconate 10% 10 mL intravenously over 10 minutes; repeat after 5 to 10 minutes if ECG changes persist (up to 3 doses). Do not mix with bicarbonate.
• Shift potassium: soluble insulin 10 units with glucose 25 g (50 mL of 50% glucose) intravenously over 15 minutes.
  • Check capillary glucose hourly for 6 hours, and give 10% glucose at 50 mL/hour for 5 hours if pre-treatment glucose is under 7 mmol/L.
  • In renal failure, hypoglycaemia is common; consider 5 units of insulin in frail or low weight patients.
• Salbutamol 10 to 20 mg nebulised over 10 minutes, additive to insulin; avoid in unstable angina or tachyarrhythmia.
• Sodium bicarbonate 1.26% 500 mL over 30 minutes only if acidosis (pH under 7.2 or bicarbonate under 18 mmol/L) and no fluid overload.
• Remove potassium:
  • Furosemide 40 to 80 mg intravenously if the patient is passing urine and not hypovolaemic.
  • Sodium zirconium cyclosilicate 10 g orally three times daily for up to 48 hours.
  • Haemodialysis if potassium stays above 6.5 mmol/L despite therapy, in oliguric kidney injury, or with ongoing tissue breakdown (refractory hyperkalaemia is an indication for renal replacement therapy).
• Recheck potassium at 1 hour, 4 hours and 24 hours after treatment; shifting agents last 4 to 6 hours and rebound occurs.

Moderate hyperkalaemia (6.0 to 6.4 mmol/L, no ECG change)

• Stop potassium retaining drugs temporarily, treat the cause, sodium zirconium cyclosilicate 10 g three times daily for up to 48 hours, loop diuretic if urine output is preserved, repeat potassium in 6 to 12 hours, and consider admission.

Mild hyperkalaemia (5.5 to 5.9 mmol/L)

• Repeat within 3 days; dietitian input; review drugs; correct acidosis with sodium bicarbonate 500 mg to 1 g two to three times daily to bicarbonate at least 22 mmol/L; loop or thiazide diuretic if volume expanded; treat constipation.

Chronic management and renoprotective drugs

• Continue ACE inhibitor or angiotensin receptor blocker if potassium is 6.0 mmol/L or less (reduce dose or stop if over 6.0 mmol/L); finerenone 10 mg daily (20 mg when eGFR is at least 60) only if potassium is under 5.0 mmol/L.
• Potassium binder to enable renin-angiotensin-aldosterone system inhibition:
  • Sodium zirconium cyclosilicate 5 to 10 g daily (maintenance; adjust at weekly intervals in 5 g steps to a maximum of 15 g daily).
  • Or patiromer 8.4 g daily with food, titrated weekly in 8.4 g steps to a maximum of 25.2 g daily; separate other oral drugs by 3 hours.
  • Monitor potassium weekly for the first month, magnesium and oedema (sodium zirconium cyclosilicate contains about 400 mg of sodium in each 5 g).
• Dietary potassium 2 to 3 g daily in advanced disease; reduce processed foods with potassium additives and salt substitutes; boil and drain vegetables.
• Dialysis patients: dialysate potassium 2 mmol/L (3 mmol/L if pre-dialysis potassium is under 4.5 mmol/L), avoid prolonged inter-dialytic interval, ensure adequate sessions, and check before the long interval.

Referral and escalation. Emergency admission for potassium 6.5 mmol/L or more or any ECG change; urgent nephrology review for oliguria; renal replacement therapy for refractory disease.

Special groups

• Children: calcium gluconate 10% 0.5 mL/kg (maximum 20 mL) intravenously over 10 minutes; insulin 0.1 units/kg with glucose 0.5 g/kg intravenously; salbutamol 2.5 to 5 mg nebulised.
• Pregnancy: avoid ACE inhibitors, angiotensin receptor blockers and finerenone; cyclosilicate has limited data.
• Transplant recipients: tacrolimus and trimethoprim are common causes; reduce dose or switch.