Initial Workup for Persistent Hyperkalemia
The initial workup for persistent hyperkalemia should include a comprehensive evaluation of medication use, renal function, assessment of acid-base status, and evaluation for endocrine disorders, with laboratory testing including serum electrolytes, renal function tests, urinalysis, and electrocardiogram. 1
Step 1: Immediate Assessment
Check ECG immediately to assess for cardiac effects of hyperkalemia:
- Mild (K+ 5.5-6.5 mmol/L): Peaked/tented T waves, nonspecific ST-segment abnormalities
- Moderate (K+ 6.5-7.5 mmol/L): PR interval prolongation, P wave flattening
- Severe (K+ >7.5 mmol/L): QRS widening, sine wave pattern, risk of ventricular fibrillation 2
Verify true hyperkalemia by ruling out:
- Hemolysis during blood collection (pseudohyperkalemia)
- Thrombocytosis or leukocytosis (pseudohyperkalemia)
- Fist clenching during blood draw
Step 2: Essential Laboratory Tests
- Complete blood count - to assess for hemoconcentration, leukocytosis, thrombocytosis
- Serum electrolytes (sodium, potassium, chloride, bicarbonate) 1
- Renal function tests (BUN, creatinine, eGFR) 1
- Urinalysis - to evaluate for hematuria, proteinuria suggesting kidney disease 1
- Blood glucose - to assess for diabetic ketoacidosis or hyperosmolar states
- Arterial blood gas - to evaluate acid-base status
- Urine potassium, creatinine, and osmolarity - to determine renal potassium handling
Step 3: Medication Review
- Identify medications that impair potassium excretion:
- RAAS inhibitors (ACEIs, ARBs, aldosterone antagonists) 1
- NSAIDs
- Calcineurin inhibitors (cyclosporine, tacrolimus)
- Potassium-sparing diuretics (spironolactone, eplerenone, amiloride, triamterene)
- Trimethoprim
- Heparin
- Beta-blockers
Step 4: Evaluate for Underlying Causes
Decreased Renal Excretion
- Chronic kidney disease - most common cause of persistent hyperkalemia 3
- Acute kidney injury - assess for recent changes in renal function
- Hyporeninemic hypoaldosteronism (Type 4 RTA) - common in diabetic nephropathy 4
- Obstructive uropathy
Transcellular Shifts
- Metabolic acidosis - most common precipitating factor 3
- Insulin deficiency or resistance
- Hypertonicity (hyperglycemia, mannitol)
- Medications causing cellular potassium release (digoxin toxicity, beta-blockers)
Increased Potassium Load
- Dietary intake - high potassium foods, salt substitutes
- Supplements - potassium supplements
- Cell lysis - tumor lysis syndrome, rhabdomyolysis, hemolysis, severe tissue trauma
Step 5: Specialized Testing (Based on Initial Findings)
- Plasma renin activity and aldosterone levels - if hyporeninemic hypoaldosteronism suspected
- 24-hour urine potassium excretion - to assess renal potassium handling
- Transtubular potassium gradient (TTKG) - to determine if hyperkalemia is due to impaired renal excretion
Special Considerations
- In patients on RAAS inhibitors: Assess the risk-benefit ratio of continuing therapy versus hyperkalemia risk 1
- In patients with heart failure: Monitor potassium levels more frequently, especially when initiating or titrating RAAS inhibitors 1
- In patients with CKD: More frequent monitoring is required as they are at higher risk for persistent hyperkalemia 5
Common Pitfalls to Avoid
- Failure to verify true hyperkalemia before initiating treatment
- Overlooking medications as potential causes
- Not considering transcellular shifts as a cause of hyperkalemia
- Inadequate follow-up monitoring after initial treatment
- Discontinuing beneficial RAAS inhibitors without trying potassium binders first 1
Remember that persistent hyperkalemia, especially with levels ≥6.5 mEq/L, is associated with increased mortality and requires thorough evaluation and management to prevent life-threatening complications 3.