Can ketones be analyzed in urine, serum, or both?

Ketone Analysis in Urine and Serum

Ketones can be analyzed in both urine and serum/blood, with each method having specific applications and limitations. 1

Blood Ketone Analysis

Types of Blood Ketone Testing

• Specific β-hydroxybutyrate (bOHB) measurement:

  • Recommended for diagnosis of diabetic ketoacidosis (DKA) 1
  • Should be used for monitoring during treatment of DKA 1
  • Requires blood samples collected into heparin, EDTA, fluoride, citrate, or oxalate 1
  • Specimens are stable at 4°C for up to 24 hours; serum/plasma specimens stable for up to 1 week at room temperature 1

• Nitroprusside-based blood ketone testing:

  • Not recommended for DKA diagnosis as it doesn't quantify bOHB (the predominant ketone in DKA) 1
  • Should not be used to monitor treatment of DKA 1
  • Only measures acetoacetate (AcAc) and sometimes acetone, but not bOHB 1
  • Can provide misleading results during DKA treatment as AcAc and acetone may increase while bOHB falls during successful therapy 1, 2

Urine Ketone Analysis

• Uses colorimetric nitroprusside reaction that detects acetoacetate (AcAc) 1
• Available in dipstick and tablet forms 1
• Does not detect bOHB, the predominant ketone body in DKA 1, 2
• False-positive results may occur with highly colored urine 1
• Positive urine ketone readings suggest possibility of impending or established DKA in patients with hyperglycemia and typical symptoms 1
• Urine ketone testing has high sensitivity and negative predictive value for DKA 1
• Positive readings can occur in non-diabetic conditions:
  • Alcoholic ketoacidosis (without hyperglycemia) 1
  • Up to 30% of first morning specimens from pregnant women 1
  • During starvation and after hypoglycemia 1

Clinical Applications and Recommendations

For DKA Diagnosis and Monitoring

1. For diagnosis: Specific measurement of bOHB in blood is recommended 1

   • DKA diagnosis requires hyperglycemia, increased blood ketone bodies/bOHB, and acidosis with increased anion gap 1
   • Urine ketone determinations alone should not be relied upon for DKA diagnosis 1

2. For monitoring treatment:

   • Blood bOHB measurement is recommended 1
   • Resolution of acidosis or reduction in blood bOHB is the marker for successful treatment 1
   • Avoid using nitroprusside-based blood ketone tests for monitoring 1

For Preventive Monitoring

• Ketosis-prone individuals should check urine or blood ketones during:
  • Illness 1
  • Deterioration in glycemic control 1
  • When using SGLT2 inhibitors (especially important as these medications can mask hyperglycemia typically seen in DKA) 1, 2

Important Considerations

• During DKA, bOHB is the predominant ketone in blood, while acetoacetate is the predominant ketone in urine 2
• As DKA resolves, bOHB is oxidized to acetoacetate, creating a lag where urine ketones might appear to increase even as DKA is resolving 2
• The ketone body ratio (3HB:AcAc) rises from normal (1:1) to as high as 10:1 in acute DKA 3
• Point-of-care devices for measuring capillary blood ketones (bOHB) have improved monitoring capabilities 4

Pitfalls to Avoid

1. Don't rely solely on urine ketone testing for DKA diagnosis 1
2. Don't use nitroprusside-based blood ketone tests to monitor DKA treatment 1
3. Be aware that urine ketone levels may lag behind clinical improvement in DKA 2
4. Remember that positive urine ketones can occur in non-diabetic conditions (pregnancy, starvation, after hypoglycemia) 1
5. Consider that SGLT2 inhibitors can cause DKA without significant hyperglycemia, making ketone monitoring particularly important 1, 2