What does the presence of urine ketones indicate?

Understanding Urine Ketones: Clinical Significance and Interpretation

The presence of urine ketones indicates a state of increased fat metabolism where the body is producing ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone) as an alternative energy source due to insufficient glucose utilization, which can signal impending or established diabetic ketoacidosis in diabetic patients or physiological ketosis in non-diabetic conditions. 1, 2

What Are Ketone Bodies?

Ketone bodies are catabolic products of free fatty acids that include:

• β-hydroxybutyrate (bOHB) - the predominant ketone in blood during ketosis
• Acetoacetate (AcAc) - the predominant ketone in urine
• Acetone - present in smaller quantities, derived from spontaneous decarboxylation of acetoacetate 1, 3

Clinical Significance of Urine Ketones

Pathological Causes

• Diabetic Ketoacidosis (DKA): The most common pathological cause of elevated ketones

  • Indicates impending or established DKA in patients with diabetes (particularly type 1)
  • Results from absolute or relative insulin deficiency with increased counterregulatory hormones 1
  • Highly sensitive for DKA with high negative predictive value 1

• SGLT2 Inhibitor-Associated Ketosis: Patients on SGLT2 inhibitors are at increased risk of developing ketosis or DKA 2

Physiological Causes

• Fasting: Prolonged periods without food
• Very Low-Carbohydrate Diets: Ketogenic diets (<20-30g carbohydrates daily)
• Prolonged Exercise: Increased energy demands
• Pregnancy: Normal physiological state
• Neonatal Period: Normal in newborns 4, 2

Interpretation of Ketone Levels

Blood Ketone Levels (β-hydroxybutyrate)

• <0.5 mmol/L: Normal range
• 0.5-1.5 mmol/L: Mild elevation (may be due to fasting or exercise)
• 1.5-3.0 mmol/L: Moderate elevation (requires monitoring)

• 3.0 mmol/L: Dangerous level (medical attention needed)

• 7.0-8.0 mmol/L: Severe ketoacidosis 2

Urine Ketones

• Normally below detection limits
• Positive results indicate increased ketone production
• During DKA resolution, urine ketones may appear to increase even as blood ketones decrease due to the shift from β-hydroxybutyrate to acetoacetate 3

Clinical Applications and Monitoring

Who Should Monitor Ketones?

• Type 1 diabetes patients: Especially those with a history of DKA
• Patients treated with SGLT2 inhibitors: Due to increased risk of DKA
• Individuals with unexplained hyperglycemia: To detect early ketosis
• Patients with symptoms of ketosis: Abdominal pain, nausea, vomiting 1, 2

When to Check Ketones

• During illness or infection ("sick days")
• With unexplained hyperglycemia
• When experiencing symptoms of ketosis
• During pregnancy with diabetes 1, 2

Clinical Management Based on Ketone Results

• Negative or trace urine ketones: Continue routine management
• Moderate to high urine ketones with hyperglycemia:
  • Implement sick day rules
  • Increase fluid intake
  • Take additional insulin as needed
  • Monitor blood glucose and ketones frequently
  • Seek medical advice if symptoms worsen or ketones increase 1
• High ketones (blood >3.0 mmol/L) with hyperglycemia:
  • Adults: IV insulin according to protocols
  • Children: Continuous insulin infusion without initial bolus 2

Important Caveats and Limitations

1. Urine ketone testing limitations:

   • Only detects acetoacetate, not β-hydroxybutyrate (the predominant ketone in DKA)
   • May show false-positive results with highly colored urine
   • Provides only semiquantitative assessment
   • Poor sensitivity for detecting mild ketosis (35-76% depending on threshold) 3, 5

2. Blood ketone testing advantages:

   • More accurate for diagnosis and monitoring of DKA
   • Measures β-hydroxybutyrate directly
   • Provides quantitative results
   • Requires only small blood samples 2, 3

3. Ketone ratio changes during treatment:

   • In acute DKA, the ketone body ratio (3HB:AcAc) rises from normal (1:1) to as high as 10:1
   • During treatment, β-hydroxybutyrate levels decrease before acetoacetate levels
   • This can lead to misleading results if only urine ketones are monitored 4

Blood ketone measurement is preferred over urine ketone testing for accurate assessment of ketosis, especially in diabetic patients at risk for DKA 2, 3.