Significance of Ketones in Urine
The presence of ketones in urine indicates increased fatty acid metabolism and may suggest impending or established diabetic ketoacidosis (DKA), especially in individuals with diabetes, although it can also represent normal physiological responses in non-diabetic individuals. 1
Clinical Significance in Different Populations
In Diabetic Patients:
- For individuals with diabetes, especially type 1 diabetes, ketones in urine suggest insufficient insulin and may indicate impending or established diabetic ketoacidosis (DKA), which is a medical emergency 1
- The presence of urine ketones is highly sensitive for DKA with high negative predictive value, making it useful for ruling out DKA 1
- Patients with type 1 diabetes should test for ketones during acute illness or stress, as recommended by the American Diabetes Association 1
- Individuals treated with SGLT2 inhibitors are at increased risk for euglycemic DKA (DKA with relatively normal blood glucose levels) 2
In Non-Diabetic Individuals:
- Ketones may represent a normal physiological response to fasting, with ketone bodies being normally present in urine and blood but usually at concentrations below detection limits 1
- Positive ketone readings can be found in up to 30% of first morning urine specimens from pregnant women 1
- Ketones may indicate compliance with low carbohydrate diets 3
- Spontaneous fasting ketonuria has been associated with a reduced risk of developing diabetes in some studies 4
Interpretation of Ketone Testing
- Blood ketone testing is preferred over urine ketone testing as it measures β-hydroxybutyrate directly, which is the predominant ketone body in DKA 1, 5
- Urine ketone tests using nitroprusside-containing reagents only detect acetoacetate and not β-hydroxybutyrate 1, 3
- During DKA, β-hydroxybutyrate is the predominant ketone in blood, while acetoacetate is the predominant ketone in urine 3
- As DKA resolves, β-hydroxybutyrate is oxidized to acetoacetate, which means urine ketone levels might increase even as DKA is resolving 3
Management Recommendations
For Diabetic Patients with Ketones:
- Increase oral fluid intake to prevent dehydration 2
- Monitor blood glucose and ketone levels every 3-4 hours 2
- Consider additional short or rapid-acting insulin if ketone levels increase or symptoms develop 2
- For patients with normal blood glucose but elevated ketones, consuming some carbohydrates along with insulin may help suppress ketone production 1
- Seek medical advice if ketone levels increase despite interventions or if symptoms of ketoacidosis develop 2
For All Patients:
- If ketones are detected, assess for symptoms of DKA including thirst, frequent urination, nausea, vomiting, abdominal pain, fruity breath odor, confusion, or difficulty breathing 6
- In patients with type 1 diabetes and ketones, evaluate for prolonged hyperglycemia which can result in DKA 6
- For non-diabetic patients with ketones, consider other causes such as fasting state, pregnancy, or low-carbohydrate diets 5
Important Caveats and Limitations
- False-positive urine ketone results can occur with highly colored urine 1
- False-positive results can also occur with several sulfhydryl drugs, including the antihypertensive drug captopril 1
- False-negative readings can occur when test strips have been exposed to air for an extended period or when urine specimens are highly acidic 1
- Currently available urine ketone tests are not reliable for diagnosing or monitoring treatment of ketoacidosis 1
- The optimal time for detecting ketonuria appears to be in the early morning and post-dinner urine 7
When to Seek Medical Attention
- Diabetic patients should seek immediate medical attention if they have ketones in urine along with:
- Pregnant individuals with elevated ketones should seek immediate medical attention due to risk of euglycemic DKA 2
- At least one urinary ketone measurement should be performed in all severely ill patients without a clear understanding of the underlying pathological processes 8