Interpreting Urine Ketone Levels: Clinical Significance and Management
Urine ketone testing is highly sensitive for detecting diabetic ketoacidosis (DKA) with excellent negative predictive value, making it valuable for ruling out DKA in patients with diabetes, though blood ketone testing (specifically β-hydroxybutyrate) is more accurate and preferred for diagnosis and monitoring of ketoacidosis. 1, 2
Normal Ketone Levels and Physiology
- Ketone bodies are normally present in urine and blood but in very low concentrations (total serum ketones <0.5 mmol/L)
- The three main ketone bodies are:
- β-hydroxybutyrate (βOHB) - most abundant in pathological states
- Acetoacetate (AcAc)
- Acetone (present in smaller quantities)
- Normally, ketone concentrations in urine are below detection limits of commercial testing methods 1
Clinical Significance of Elevated Ketones
Pathological Causes
- Diabetic ketoacidosis (DKA) - most common pathological cause 1, 3
- Indicates impending or established DKA, a medical emergency
- Results from absolute or relative insulin deficiency and increased counterregulatory hormones
- In acute DKA, the ketone body ratio (βOHB:AcAc) rises from normal (1:1) to as high as 10:1 4
Non-Pathological Causes
- Fasting or prolonged exercise
- Pregnancy (up to 30% of first morning urine specimens may show positive ketones) 3
- Very-low-carbohydrate (ketogenic) diets 1, 5
Interpretation of Urine Ketone Results
Diagnostic Value
- Highly sensitive for DKA detection (sensitivity 99%, 95% CI 97-100%)
- Excellent negative predictive value (100%, 95% CI 99-100%) for excluding DKA 2
- Lower specificity (69%, 95% CI 66-73%) means positive results require further evaluation 2
Limitations of Urine Ketone Testing
- Detects primarily acetoacetate, not β-hydroxybutyrate (the predominant ketone in DKA)
- May underestimate total ketone body concentration in DKA 1
- False-positive results can occur with:
- Highly colored urine
- Sulfhydryl drugs (including captopril)
- False-negative results can occur with:
Blood vs. Urine Ketone Testing
Blood Ketone Testing Advantages
- Measures β-hydroxybutyrate directly, which is the predominant ketone in DKA
- More accurate for total ketosis assessment
- Preferred for diagnosis and monitoring of ketoacidosis 3
- Children randomized to blood ketone testing had almost half the number of emergency department visits or hospitalizations compared to urine ketone testing 1
When to Use Each Method
- Blood ketone testing: Preferred for diagnosis and monitoring of DKA
- Urine ketone testing: Useful as a screening tool due to high sensitivity and negative predictive value 2
Recommendations for Ketone Testing
Who Should Test
- Individuals prone to ketosis should measure ketones when indicated:
When to Test
- During unexplained hyperglycemia (>300 mg/dL or >16.7 mmol/L)
- When experiencing symptoms of ketosis (abdominal pain, nausea)
- During acute illness or stress
- During pregnancy with pre-existing diabetes or gestational diabetes
- When any symptoms of ketoacidosis are present 1
Action Based on Results
- Implement sick day rules if ketones are elevated:
- Oral hydration
- Additional short/rapid-acting insulin and oral carbohydrates
- Frequent monitoring of blood glucose and ketones
- Seek medical advice if symptoms worsen or ketone concentrations increase
- Present to emergency room if sufficient oral hydration cannot be maintained due to vomiting or mental status changes 1
Future Directions
Continuous ketone monitoring (CKM) via interstitial fluid is emerging as a promising technology that may provide real-time ketone readings every 5 minutes, potentially benefiting those at high risk of DKA, including people with type 1 diabetes, pregnant women, those on SGLT2 inhibitors, and individuals on low-carbohydrate diets 6.