What does the presence of ketones in the urine indicate?

Ketones in Urine: Clinical Significance and Interpretation

The presence of ketones in urine primarily indicates that the body is breaking down fat for energy instead of using glucose, which may signal impending or established diabetic ketoacidosis (DKA), a potentially life-threatening condition requiring immediate medical attention. 1

What Are Ketones?

• Ketone bodies are produced by the liver when glucose is not readily available as an energy source
• Three main ketone bodies exist:
  • Beta-hydroxybutyrate (3HB) - the predominant ketone in DKA
  • Acetoacetate (AcAc)
  • Acetone (least abundant)

Normal vs. Abnormal Ketone Levels

• Ketones are normally present in urine but usually below detectable levels 2
• Positive ketone readings can be found in:
  • Normal individuals during fasting
  • Up to 30% of first morning urine specimens from pregnant women 2, 1
  • During prolonged exercise
  • In neonates

Clinical Significance of Ketones in Urine

Diabetic Ketoacidosis

• Most serious cause of elevated ketones
• Occurs due to insulin deficiency and elevated counterregulatory hormones
• Characterized by:
  • Blood glucose >250 mg/dL (though euglycemic DKA can occur)
  • Metabolic acidosis (pH <7.3, bicarbonate <15 mEq/L)
  • Elevated ketones in blood or urine 1

Other Causes of Ketonuria

1. Physiologic:

   • Fasting/starvation
   • Low-carbohydrate diets
   • Prolonged exercise
   • Pregnancy

2. Pathologic:

   • Alcoholic ketoacidosis (hyperketonemia without hyperglycemia) 3
   • SGLT2 inhibitor use (can cause euglycemic DKA) 4
   • Severe illness or stress

When to Test for Ketones

Ketone testing is particularly important for:

• Type 1 diabetes patients
• Pregnant women with pre-existing or gestational diabetes
• During acute illness or stress
• When blood glucose levels are consistently elevated (>300 mg/dL)
• When symptoms of ketoacidosis are present (nausea, vomiting, abdominal pain) 2, 1
• SGLT2 inhibitor users (should measure ketones at any sign of illness regardless of glucose levels) 1

Limitations of Urine Ketone Testing

• Urine ketone tests (nitroprusside method) only detect acetoacetate and acetone, not beta-hydroxybutyrate, which is the predominant ketone in DKA 5, 6
• During treatment of DKA, beta-hydroxybutyrate is converted to acetoacetate, which can make urine ketone tests appear to worsen even as the condition improves 6
• False-positive results can occur with:
  • Sulfhydryl drugs (including captopril) 2, 1
  • Highly colored urine
• False-negative results can occur with:
  • Test strips exposed to air for extended periods
  • Highly acidic urine (e.g., after large intakes of ascorbic acid) 2
  • Delayed testing (ketones can degrade in urine samples)

Clinical Recommendations

• Blood ketone testing methods that quantify beta-hydroxybutyrate are preferred over urine ketone testing for diagnosing and monitoring ketoacidosis 2, 1
• Urine ketone tests are not reliable for diagnosing or monitoring treatment of ketoacidosis 2
• Home monitoring supplies for beta-hydroxybutyrate should be provided to high-risk patients 1
• Immediate action is required when ketones are elevated, including:
  • Frequent blood glucose and ketone monitoring
  • Hydration
  • Insulin administration 1

Warning Signs Requiring Urgent Medical Attention

• Elevated ketones with symptoms such as:
  • Nausea or vomiting
  • Abdominal pain
  • Difficulty breathing
  • Fruity-smelling breath
  • Confusion or extreme fatigue
• These may indicate developing or established DKA requiring emergency treatment 1, 7

Remember that ketones in urine can be an early warning sign of metabolic decompensation, particularly in diabetes, and should never be ignored in at-risk populations.