What level of ketones in urine is considered ketonuria?

Defining Ketonuria: Threshold for Ketones in Urine

Ketonuria is defined as the presence of ketone bodies in urine at a level of 1+ or greater on a urine dipstick test, which corresponds to approximately 10-20 mg/dL of ketones. 1

Understanding Ketone Bodies and Their Detection

• Ketone bodies (acetoacetate, acetone, and β-hydroxybutyrate) are normally present in urine and blood but at very low concentrations, typically below the detection limits of routine testing methods 2
• Standard urine dipsticks use the nitroprusside reaction, which produces a purple color when reacting with acetoacetate and acetone, but importantly does not measure β-hydroxybutyrate (bOHB) 2, 3
• The nitroprusside method is much more sensitive to acetoacetate than acetone with respect to color generation 2
• Semi-quantitative urine ketone measurements typically report results as negative, trace, 1+, 2+, 3+, or 4+ 1

Clinical Significance of Different Ketone Levels

• Negative: No detectable ketones or below the threshold of detection 1
• Trace: Minimal ketones present, usually not clinically significant 1
• 1+ (10-20 mg/dL): Indicates mild ketosis, which may be physiological or pathological depending on clinical context 1
• 2+ (30-40 mg/dL): Moderate ketosis, requires clinical correlation 1, 4
• 3+ (≥80 mg/dL): Significant ketosis, strongly suggestive of diabetic ketoacidosis (DKA) when accompanied by hyperglycemia and acidosis 1, 4

Clinical Context for Interpreting Ketonuria

• In diabetic patients, especially those with type 1 diabetes, even 1+ ketones may suggest impending or established DKA, which is a medical emergency 2, 1
• Positive ketone readings (≥1+) can be found in normal individuals during fasting and in up to 30% of first morning urine specimens from pregnant women 2, 3
• At a two-cross (2+) cutoff point for ketonuria, the sensitivity for detecting ketoacidosis is 100%, but specificity is only 77% 4
• The presence of urine ketones is highly sensitive for DKA with high negative predictive value, making it useful for ruling out DKA 2

Limitations of Urine Ketone Testing

• Urine dipsticks do not measure β-hydroxybutyrate, which is often the predominant ketone body in DKA 2, 3
• This limitation can lead to underestimation of total ketone body concentration in ketoacidosis 2
• False-positive results can occur with highly colored urine 1, 3
• 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

Blood Ketone Testing vs. Urine Ketone Testing

• Blood β-hydroxybutyrate (bOHB) measurement is more accurate than urine ketone testing, as bOHB is the predominant ketone body in DKA 2, 5
• A blood bOHB value lower than 3 mmol/L enables ketoacidosis to be excluded (negative predictive value 100%) 4
• At the 3 mmol/L cutoff point for blood ketonemia, the sensitivity is 100% and specificity is 94%, which is significantly higher than that of urine ketone testing (77% specificity) 4
• Abnormal plasma bOHB levels without ketonuria are prevalent in poorly controlled diabetics, with 43% of abnormal bOHB values not associated with ketonuria 6

Clinical Recommendations

• For ketosis-prone individuals (those with type 1 diabetes, history of DKA, or treated with SGLT2 inhibitors), even mild ketonuria (1+) requires monitoring and potential intervention 2, 1
• Blood ketone testing is preferred over urine ketone testing as it measures β-hydroxybutyrate directly 2, 5
• Diagnosis of DKA in clinical settings should not rely solely on urine ketone determinations but requires the presence of hyperglycemia, increased blood ketone bodies or bOHB, and acidosis with increased anion gap 2
• Currently available urine ketone tests are not reliable for diagnosing or monitoring treatment of ketoacidosis 2, 1