Are urinary ketones (urine ketones) reliable for monitoring diabetic ketoacidosis (DKA)?

Urinary Ketones Are Not Reliable for Monitoring Diabetic Ketoacidosis

Urinary ketones should not be used for monitoring diabetic ketoacidosis (DKA) as they fail to measure beta-hydroxybutyrate (bOHB), the predominant ketone in DKA, and can be misleading during treatment.

Limitations of Urine Ketone Testing

• Urine ketone tests using nitroprusside reaction only detect acetoacetate (AcAc) and not beta-hydroxybutyrate (bOHB), which is the predominant ketone body in DKA 1
• During DKA treatment, as the patient improves, bOHB is converted to AcAc, which can paradoxically cause urine ketone readings to increase even as the clinical condition improves 2
• False-positive results can occur with highly colored urine samples 1, 3
• False-negative readings can occur when test strips have been exposed to air for an extended period or when urine specimens are highly acidic 4
• Positive urine ketone readings can be found in up to 30% of first morning urine specimens from pregnant women, during starvation, and after hypoglycemia, making interpretation challenging 1, 3

Recommended Approach for DKA Monitoring

• Specific measurement of blood beta-hydroxybutyrate (bOHB) should be used for diagnosis of DKA and for monitoring during treatment 1
• Blood bOHB measurements show better correlation with the degree of acidosis (pH and HCO3) compared to urinary ketones 5
• For diagnosis of DKA, the American Diabetes Association recommends using blood bOHB levels (preferred cutoff ≥6.3 mmol/L) in combination with evidence of metabolic acidosis (venous pH <7.3 and serum bicarbonate <18 mEq/L) 6
• During treatment, monitoring should include blood glucose, electrolytes, BUN, creatinine, venous pH, anion gap, and blood bOHB levels every 2-4 hours 6

Clinical Significance of Ketone Measurements

• In patients with diabetes presenting with typical symptoms and hyperglycemia, positive urine ketone readings only suggest the possibility of impending or established DKA but are not sufficient for diagnosis 1
• Diagnosis of DKA requires the presence of hyperglycemia, increased blood ketone bodies (particularly bOHB), and acidosis with increased anion gap 1, 6
• While urine ketone tests have high negative predictive value (can help rule out DKA when negative), they have poor positive predictive value for confirming DKA 7

Emerging Technologies for Ketone Monitoring

• Point-of-care tests for blood ketone measurement are now widely available and provide more accurate assessment of ketosis 2
• Continuous ketone monitoring (CKM) via interstitial fluid is an emerging technology that may provide more comprehensive monitoring for patients at risk of DKA 8
• CKM could be particularly beneficial for individuals with type 1 diabetes, pregnant patients, those on SGLT2 inhibitors, people with recurrent DKA, and those on low carbohydrate diets 8

Special Considerations

• For patients on SGLT2 inhibitors, which can cause euglycemic DKA, blood ketone monitoring is especially important as these medications can decrease the hyperglycemia typically associated with DKA 1
• In patients unable to access blood ketone testing, urine ketone testing combined with other clinical and laboratory parameters (blood glucose, pH, bicarbonate, anion gap) may be used, but with clear understanding of its limitations 9

Practical Algorithm for DKA Monitoring

1. Use blood bOHB measurement as the primary method for diagnosing and monitoring DKA 1
2. Monitor blood bOHB levels every 2-4 hours during DKA treatment 6
3. Consider DKA resolution when anion gap normalizes (≤12 mEq/L), serum bicarbonate reaches ≥18 mEq/L, venous pH >7.3, and blood bOHB levels decrease 6
4. If blood ketone testing is unavailable, use urine ketone testing with caution, understanding that values may paradoxically increase during successful treatment 2
5. Never rely solely on urine ketone measurements to guide DKA treatment decisions 1