What is the expected serum beta-hydroxybutyrate (bOHB) level in a patient with ketones in their urine?

Relationship Between Urine Ketones and Serum Beta-Hydroxybutyrate Levels

Urine ketone measurements do not reliably correlate with serum beta-hydroxybutyrate (bOHB) levels, as urine tests only detect acetoacetate and sometimes acetone, but not bOHB which is the predominant ketone body in diabetic ketoacidosis (DKA). 1

Understanding Ketone Body Measurement

Types of Ketone Bodies

• Beta-hydroxybutyrate (bOHB) - predominant ketone in DKA
• Acetoacetate (AcAc)
• Acetone (in smaller quantities)

Testing Methods

1. Urine ketone testing:

   • Uses nitroprusside reaction (dipsticks/tablets)
   • Only detects acetoacetate and sometimes acetone
   • Cannot detect bOHB 1
   • Qualitative rather than quantitative

2. Blood ketone testing:

   • Specific bOHB measurement is recommended for DKA diagnosis
   • Quantitative measurement
   • More accurate reflection of ketosis severity

Correlation Between Urine Ketones and Serum bOHB

Research shows significant discordance between urine ketone measurements and actual serum bOHB levels:

• In children, a serum bOHB level of ≥3.0 mmol/L corresponds to the threshold for DKA diagnosis 2
• In adults, a serum bOHB level of ≥3.8 mmol/L corresponds to the threshold for DKA diagnosis 2

Important Clinical Considerations:

• Patients may have significant elevations in serum bOHB even when urine ketones appear to be clearing 3
• The equilibrium between AcAc and bOHB shifts toward bOHB in conditions that alter the redox state of hepatic mitochondria (hypoxia, fasting, DKA, alcoholic ketoacidosis) 1
• This shift means urine ketone tests may significantly underestimate total ketone body concentration 1

Clinical Implications

• For diagnosis: Blood bOHB testing is superior to urine ketone testing for DKA diagnosis 1, 4

  • At a 3 mmol/L cutoff point for serum bOHB, sensitivity is 100% with specificity of 94% 4
  • At a 5 mmol/L cutoff point for serum bOHB, positive predictive value reaches 100% 4

• For monitoring: Blood bOHB measurements should be used rather than urine ketones 1

  • Urine ketones may become positive during recovery as bOHB converts to acetoacetate 1
  • This can lead to misleading clinical information during treatment

Pitfalls in Ketone Measurement

• False reassurance: Negative or low urine ketones may occur despite high serum bOHB levels
• Treatment confusion: During DKA treatment, as bOHB decreases, AcAc may increase, causing urine ketones to appear to worsen while the patient is actually improving 1
• Delayed detection: Urine testing may take longer to obtain results (median 21 minutes, >2 hours in 10% of cases) 4
• Common attempts to improve urine testing such as using hydrogen peroxide, alkalinization, or silver nitrate catalysts do not improve clinically meaningful urine bOHB detection 5

Blood bOHB testing has been shown to reduce emergency department assessments, hospitalizations, time to recovery from DKA, and potentially lower healthcare expenditure compared to urine ketone testing 6.