Ketones in Urine: Clinical Significance and Management
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. 1, 2
What Are Ketones?
- Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available 3
- The principal ketone bodies are beta-hydroxybutyrate (bOHB) and acetoacetate (AcAc), with acetone present in smaller quantities 4
- Normally, ketones are present in blood and urine at concentrations below detection limits of routine testing methods 1
Clinical Significance of Urine Ketones
In Diabetic Patients:
- Ketones in urine are highly sensitive for detecting DKA with high negative predictive value, making urine ketone testing useful for ruling out DKA 4, 1
- For individuals with diabetes, especially type 1 diabetes, elevated ketones suggest insufficient insulin and may indicate impending or established DKA, which is a medical emergency 1, 5
- Inadequate insulin dosing or discontinuation of treatment may lead to hyperglycemia and, in patients with type 1 diabetes, diabetic ketoacidosis 5
In Non-Diabetic Individuals:
- Positive ketone readings can be found in normal individuals during fasting states 1, 3
- Ketones may be present in up to 30% of first morning urine specimens from pregnant women 1
- Ketosis is normal during prolonged exercise and when consuming a high-fat diet 6
Interpretation of Ketone Testing
- Urine ketone tests using nitroprusside-containing reagents only detect acetoacetate and not β-hydroxybutyrate, which may underestimate total ketone body concentration 4, 1
- During DKA, the ratio of bOHB:AcAc rises from normal (1:1) to as high as 10:1, making bOHB the predominant ketone body 3, 7
- Blood ketone testing is preferred over urine ketone testing as it measures β-hydroxybutyrate directly 4, 1, 2
- As DKA resolves with treatment, bOHB is oxidized to acetoacetate, which can cause urine ketone tests to show increasing levels even as the condition improves 7
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 4, 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 1, 2
Special Considerations:
- Individuals treated with SGLT2 inhibitors are at increased risk for DKA, even with relatively normal blood glucose levels (euglycemic DKA) 2
- Pregnant individuals may present with euglycemic DKA and should seek immediate medical attention if ketones are elevated 2
- Hypoalbuminemic patients with diabetes may have a higher risk of developing ketosis 8
Important Caveats and Limitations
- False-positive urine ketone results can occur with highly colored urine 4, 1
- False-negative readings can occur when test strips have been exposed to air for an extended period 1
- False-negative readings can also occur when urine specimens are highly acidic 1
- Currently available urine ketone tests are not reliable for diagnosing or monitoring treatment of ketoacidosis 1
- Blood ketone determinations that rely on the nitroprusside reaction should not be used to monitor treatment of DKA 4
Warning Signs Requiring Medical Attention
- Symptoms of DKA include nausea, vomiting, drowsiness, flushed dry skin, dry mouth, increased urination, thirst, loss of appetite, and acetone breath 5
- Severe symptoms such as altered mental status, inability to tolerate oral hydration due to vomiting, or persistently elevated ketone levels despite interventions require immediate medical attention 2, 5