What is the initial workup for a patient with hyperkalemia by a nephrologist?

Nephrologist Workup for Hyperkalemia

The nephrologist workup for hyperkalemia should systematically exclude pseudohyperkalemia, assess cardiac risk with ECG, identify the underlying mechanism through targeted laboratory testing, and review all contributing medications—particularly RAAS inhibitors—while determining whether acute intervention or chronic management strategies are needed. 1

Initial Verification and Risk Stratification

Exclude Pseudohyperkalemia

• Repeat the potassium measurement with proper technique or obtain an arterial sample to rule out pseudohyperkalemia from hemolysis, repeated fist clenching, or poor phlebotomy technique before initiating any treatment 1, 2
• Pseudohyperkalemia is a critical pitfall that can lead to unnecessary interventions 1

Obtain Immediate ECG

• Perform ECG immediately to detect life-threatening changes: peaked T waves, flattened P waves, prolonged PR interval, widened QRS complexes 1, 2
• ECG changes indicate urgent treatment regardless of the absolute potassium level 1
• ECG findings can be highly variable and less sensitive than laboratory tests, so their absence does not exclude significant hyperkalemia 1

Classify Severity

• Mild hyperkalemia: 5.0-5.9 mEq/L 1
• Moderate hyperkalemia: 6.0-6.4 mEq/L 1
• Severe hyperkalemia: ≥6.5 mEq/L 1

Comprehensive Laboratory Assessment

Renal Function Evaluation

• Measure serum creatinine and calculate eGFR to assess kidney function, as impaired renal potassium excretion is the dominant cause of sustained hyperkalemia 1, 2, 3
• Reduced kidney function (eGFR <50 mL/min) substantially increases hyperkalemia risk 2
• Check for acute kidney injury (AKI), particularly in the setting of sepsis/infection, as all cases of hyperkalemia-induced cardiac arrest in one study had AKI present 2

Urine Studies

• Obtain urine potassium, creatinine, and osmolarity as the first step in determining the cause of hyperkalemia, which directs long-term treatment 4
• These studies help differentiate between renal and extrarenal causes of hyperkalemia 3

Additional Laboratory Tests

• Measure serum glucose to detect hyperglycemia, which causes transcellular potassium shifts due to hyperosmolarity and insulin deficiency 2
• Check arterial blood gas or serum bicarbonate to identify metabolic acidosis, which shifts potassium from intracellular to extracellular space 1, 2
• Assess serum sodium as hyponatremia may indicate volume depletion or renal dysfunction, both impairing potassium excretion 2

Medication Review

Systematically Evaluate All Medications

RAAS inhibitors are the most common culprits and require careful assessment 1, 2:

• ACE inhibitors 1, 2
• ARBs 1, 2
• Mineralocorticoid receptor antagonists (spironolactone) 1, 2
• Sacubitril/valsartán 2

Other potassium-retaining medications 1, 2:

• Potassium-sparing diuretics (amiloride, triamterene) 1, 2
• NSAIDs (commonly used for pain/infection, reduce renal potassium excretion) 1, 2
• Beta-blockers 1, 2
• Trimethoprim-sulfamethoxazole 1, 2
• Heparin and derivatives 1, 2
• Calcineurin inhibitors (cyclosporine, tacrolimus) 2

Dietary sources 1, 2:

• Potassium supplements 1, 2
• Salt substitutes (high potassium content) 1, 2

Critical Pitfall

Do not permanently discontinue RAAS inhibitors in patients with cardiovascular disease, heart failure, or proteinuric CKD, as these medications provide mortality benefit and slow disease progression 1, 5

Identify Underlying Mechanisms

Three Primary Mechanisms 2

1. Impaired Renal Potassium Excretion (most common) 3:

• Chronic kidney disease 1, 2
• Acute kidney injury 2
• Reduced distal sodium and water delivery to the nephron 3
• Hyporeninemic hypoaldosteronism (common in diabetic nephropathy) 4

2. Transcellular Potassium Shift 2:

• Metabolic acidosis 1, 2
• Hyperglycemia with insulin deficiency 2
• Tissue breakdown (rhabdomyolysis, tumor lysis syndrome) 1

3. Excessive Potassium Intake (only in setting of impaired renal function) 2, 3:

• High-potassium diet 2
• Potassium supplements or salt substitutes 1, 2

Assess Comorbidities and Risk Factors

High-Risk Conditions

• Diabetes mellitus increases hyperkalemia risk, particularly with diabetic nephropathy and hyporeninemic hypoaldosteronism 1, 2, 4
• Heart failure patients require RAAS inhibitors but are at increased risk for hyperkalemia 1, 6
• Chronic kidney disease is the most common underlying condition 1, 6, 7
• Advanced age combined with renal insufficiency and diabetes increases risk 2

Rate of Potassium Rise

• The rate of potassium increase is as important as the absolute value—rapid increases are more dangerous than gradual elevations 1
• Acute hyperkalemia requires immediate attention due to potentially life-threatening cardiac manifestations 5

Monitoring Protocol

Initial Monitoring

• Check potassium within 1 week of starting or escalating RAAS inhibitors 1
• Reassess potassium 7-10 days after dose changes in patients on RAAS inhibitors 1

Ongoing Monitoring

• Individualize monitoring frequency based on eGFR, heart failure status, diabetes, and history of hyperkalemia 1
• High-risk patients (CKD, diabetes, heart failure, prior hyperkalemia) require more frequent monitoring 1, 2
• Monitor potassium every 2-4 hours after acute interventions in severe hyperkalemia (>6.5 mEq/L) or ongoing potassium release states 1

Determine Management Strategy

Acute vs. Chronic Hyperkalemia

Acute hyperkalemia 5:

• Requires immediate cardiac membrane stabilization with IV calcium if ECG changes present 1
• Followed by intracellular potassium shifting with insulin/glucose and beta-agonists 1
• Ultimately requires strategies to decrease total body potassium (diuretics, dialysis, binders) 1, 5

Chronic hyperkalemia 5:

• Focus on medication optimization, not discontinuation of RAAS inhibitors 1, 5
• Initiate newer potassium binders (patiromer or sodium zirconium cyclosilicate) to maintain RAAS inhibitor therapy 1, 5
• Ensure effective diuretic therapy and correct metabolic acidosis if present 5
• Avoid stringent dietary potassium restrictions—evidence linking dietary intake to serum levels is limited, and potassium-rich diets provide cardiovascular benefits 1, 5

Common Pitfalls to Avoid

• Do not treat without excluding pseudohyperkalemia first 1, 2
• Do not rely solely on ECG findings—they are variable and less sensitive than laboratory tests 1
• Do not use sodium bicarbonate without metabolic acidosis—it is only indicated when acidosis is present (pH <7.35, bicarbonate <22 mEq/L) 1
• Do not permanently discontinue RAAS inhibitors—use potassium binders to maintain these life-saving medications 1, 5
• Do not delay ECG in moderate to severe hyperkalemia 2
• Do not forget to monitor for AKI in acute presentations, especially with infection/sepsis 2

Team Approach

Optimal chronic hyperkalemia management involves a multidisciplinary team: nephrologists, cardiologists, primary care physicians, nurses, pharmacists, social workers, and dietitians 1