What is the appropriate approach to diagnose and manage ketonuria?

Diagnosis and Management of Ketonuria

When ketonuria is detected, immediately check blood glucose to distinguish benign starvation ketosis from life-threatening diabetic ketoacidosis (DKA), as this single test determines whether urgent intervention is needed. 1, 2

Initial Diagnostic Algorithm

Step 1: Measure Blood Glucose Immediately

• If glucose >250 mg/dL with ketones present: This is a medical emergency requiring immediate DKA evaluation 1, 2
• If glucose <250 mg/dL or normal: Most likely starvation ketosis from reduced caloric intake, particularly during illness or fasting 1, 3

Step 2: Use Blood Ketone Testing, Not Urine

Blood beta-hydroxybutyrate measurement is strongly preferred over urine testing for all clinical decision-making because urine dipsticks only detect acetoacetate and significantly underestimate total ketone concentration, missing beta-hydroxybutyrate which is the predominant ketone body in DKA. 4, 1, 2

• Urine ketone tests are unreliable for diagnosing or monitoring treatment of ketoacidosis 4
• The nitroprusside method (standard urine dipstick) does not measure beta-hydroxybutyrate at all 1

Blood Ketone Action Thresholds

For patients with diabetes, use these specific cutoffs for beta-hydroxybutyrate: 1, 2

• <0.5 mmol/L: No intervention needed
• 0.5-1.5 mmol/L: Initiate sick-day rules (oral hydration, additional short-acting insulin, oral carbohydrates, frequent monitoring)
• ≥1.5 mmol/L: Immediate medical attention and likely IV insulin required

Complete DKA Diagnostic Criteria

All of the following must be present to diagnose DKA: 1, 2

• Plasma glucose >250 mg/dL
• Arterial pH <7.30 (venous pH <7.3 acceptable)
• Serum bicarbonate <15 mEq/L
• Positive ketones (preferably blood beta-hydroxybutyrate)
• Anion gap >10 mEq/L

When to Test for Ketones

Type 1 diabetes patients should test for ketones during: 4

• Blood glucose consistently >300 mg/dL (>16.7 mmol/L)
• Acute illness or stress
• Pregnancy
• Symptoms of ketoacidosis (nausea, vomiting, abdominal pain)

High-risk patients requiring immediate evaluation include: 1

• Known type 1 diabetes
• History of prior DKA
• Currently on SGLT2 inhibitors (can cause euglycemic DKA with glucose <250 mg/dL)
• Unexplained hyperglycemia or symptoms of ketosis

Differential Diagnosis of Ketonuria

Starvation Ketosis (Most Common in Non-Diabetics)

• Normal or low blood glucose 1, 3
• Serum bicarbonate usually not lower than 18 mEq/L 1, 3
• Blood ketones 0.3-4 mmol/L with normal pH 3
• Recent decreased oral intake 1
• No abdominal pain or altered mental status 1

Diabetic Ketoacidosis

• Glucose typically >250 mg/dL (but can be lower with SGLT2 inhibitors) 1
• Ketones >7-8 mmol/L 3
• Low pH, low bicarbonate 1
• Often precipitated by infection (50% of cases), particularly urinary tract infections 1

Alcoholic Ketoacidosis

• Positive urine ketones but hyperglycemia usually not present 1
• May have hematuria from trauma or coagulopathy 1

Important Caveats and Pitfalls

False-positive results occur with: 4, 2

• Sulfhydryl drugs including captopril (antihypertensive)

False-negative results occur with: 4, 2

• Test strips exposed to air for extended periods
• Highly acidic urine (after large ascorbic acid intake)

Physiologic ketonuria is common and benign: 4, 1

• Up to 30% of first morning urine specimens from pregnant women show positive ketones
• Normal individuals during fasting states
• After hypoglycemic episodes 1

Management Based on Diagnosis

For Confirmed DKA

Start continuous IV regular insulin infusion at 0.1 units/kg/hour, target glucose decline of 50-75 mg/dL per hour, and provide 1.5 times the 24-hour maintenance fluid requirements. 2

For Starvation Ketosis

• Encourage oral hydration and carbohydrate intake 3
• For diabetic patients: consume carbohydrates along with insulin to suppress ketone production 2, 3

Special Consideration: SGLT2 Inhibitors

SGLT2 inhibitors decrease the hyperglycemia that typically accompanies DKA, making diagnosis more challenging and can cause euglycemic DKA where glucose may be <250 mg/dL despite severe ketoacidosis. 1 These patients require immediate evaluation for pathological ketosis even with lower glucose levels. 1