Significance and Management of Ketones in Urine
Ketones in urine indicate increased fatty acid metabolism and require immediate assessment for diabetic ketoacidosis (DKA) in individuals with diabetes, while in non-diabetic individuals they typically represent physiologic starvation ketosis from fasting or pregnancy. 1, 2
Clinical Significance
In Diabetic Patients
- Urine ketones are highly sensitive for DKA with high negative predictive value, making them useful for ruling out DKA but not for monitoring treatment. 1, 2
- Even mild ketonuria (1+ ketones) in ketosis-prone individuals (type 1 diabetes, history of DKA) suggests insufficient insulin and may indicate impending or established DKA, which is a medical emergency. 2, 3
- Individuals treated with SGLT2 inhibitors are at increased risk for euglycemic DKA (DKA with relatively normal blood glucose levels), making ketone monitoring particularly critical in this population. 3, 4
In Non-Diabetic Individuals
- Up to 30% of first morning urine specimens from pregnant women show positive ketones as a normal physiologic finding due to fasting or nausea/vomiting. 2, 5
- Positive ketone readings can occur in normal individuals during fasting states. 2
Critical Limitations of Urine Ketone Testing
Urine ketone tests using nitroprusside-containing reagents only detect acetoacetate and acetone, NOT β-hydroxybutyrate, which is the predominant ketone body in DKA. 1, 2, 6
Key Pitfalls
- This limitation may severely underestimate total ketone body concentration and provide misleading clinical information. 1, 5
- As DKA resolves, β-hydroxybutyrate is oxidized to acetoacetate, causing urine ketones to paradoxically increase even as the patient improves. 6
- False-positive results can occur with highly colored urine and sulfhydryl drugs including captopril. 2
- False-negative results can occur with expired test strips or highly acidic urine specimens. 2
Management Algorithm
For Diabetic Patients with Positive Urine Ketones
Immediate Actions:
- Increase oral fluid intake to prevent dehydration. 2, 3
- Monitor blood glucose and ketone levels every 3-4 hours. 2, 3
- Administer additional short or rapid-acting insulin if blood glucose is elevated. 2, 3
- For patients with normal blood glucose but elevated ketones, consume carbohydrates along with insulin to suppress ketone production. 2
Seek Emergency Medical Attention If:
- Unable to tolerate oral hydration due to vomiting. 3
- Blood glucose levels do not improve with insulin administration. 3
- Altered mental status develops. 3, 7
- Ketone levels continue to increase despite interventions. 3
- Symptoms of DKA develop: abdominal pain, nausea, vomiting, fruity breath odor, heavy breathing, rapid pulse. 7
For Pregnant Women with Ketonuria
- Measure blood glucose immediately to rule out undiagnosed diabetes. 5
- Check for DKA symptoms (abdominal pain, nausea, vomiting, altered mental status). 5
- Blood β-hydroxybutyrate is the preferred test over urine ketones for diagnosing DKA in pregnancy. 5
- For physiologic starvation ketosis, increase oral fluid and carbohydrate intake with close monitoring. 5
- Pregnant individuals may present with euglycemic DKA and should seek immediate medical attention if ketones are elevated. 3
Preferred Testing Method
Blood ketone testing that measures β-hydroxybutyrate is strongly preferred over urine ketone testing for diagnosis and monitoring of DKA. 1, 3
Advantages of Blood Ketone Testing
- Directly measures β-hydroxybutyrate, the predominant ketone in DKA. 1, 6
- Children with type 1 diabetes using blood ketone testing had almost half the number of emergency department visits or hospitalizations compared to urine ketone testing. 1
- Blood ketone determinations using nitroprusside should NOT be used to monitor DKA treatment. 1
Special Populations Requiring Ketone Monitoring
The American Diabetes Association recommends that ketosis-prone individuals check urine or blood ketones during:
- Acute illness or infection. 1, 3
- Symptoms of deteriorating glycemic control. 1
- Blood glucose exceeding target thresholds. 3
- Nausea, vomiting, or malaise. 1, 3
High-risk groups include: