What does the presence of ketones and blood in the urine indicate, especially in a diabetic patient?

Ketones and Blood in Urine: Clinical Significance

In diabetic patients, the presence of ketones and blood in urine most likely indicates diabetic ketoacidosis (DKA) or impending DKA—a life-threatening emergency requiring immediate medical evaluation with blood glucose, blood beta-hydroxybutyrate, electrolytes, and arterial blood gas. 1, 2

Immediate Assessment Algorithm

When ketones and blood appear together in a diabetic patient's urine, follow this structured approach:

Step 1: Measure Blood Glucose Immediately

• If glucose >250 mg/dL: This indicates a medical emergency requiring immediate DKA evaluation 1, 2
• Obtain blood beta-hydroxybutyrate, electrolytes, and arterial blood gas without delay 1
• DKA diagnostic criteria require: glucose >250 mg/dL, arterial pH <7.30, serum bicarbonate <15 mEq/L, positive ketones, and anion gap >10 mEq/L 2

Step 2: Assess High-Risk Features

High-risk patients requiring immediate evaluation include: 2

• Known type 1 diabetes
• History of prior DKA episodes
• Currently taking SGLT2 inhibitors (which can cause euglycemic DKA with glucose <250 mg/dL despite severe ketoacidosis) 2
• Presenting with nausea, vomiting, abdominal pain, or altered mental status 3, 4

Step 3: Recognize Testing Limitations

Critical pitfall: Urine dipsticks only detect acetoacetate, NOT beta-hydroxybutyrate, which is the predominant ketone body in DKA and can significantly underestimate total ketone concentration. 1, 2, 5

• Blood ketone testing is strongly preferred over urine testing for all clinical decision-making 1, 2
• Urine ketone tests can show false-positives with sulfhydryl drugs like captopril 3, 1
• False-negatives occur with prolonged air exposure of test strips or highly acidic urine 3, 1
• As DKA resolves, urine ketones may paradoxically increase even while blood ketones are decreasing, because beta-hydroxybutyrate converts to acetoacetate during recovery 5

Differential Diagnosis Considerations

Pathological Ketosis (DKA)

• Very high ketone bodies (>7-8 mmol/L), low systemic pH, hyperglycemia typically present 6
• Precipitated by infection (50% of cases), insulin omission, or new-onset diabetes 2, 6
• Presents with polyuria, polydipsia, weakness, abdominal pain, Kussmaul respirations, fruity breath odor 2, 4

Benign Starvation Ketosis

• Serum bicarbonate usually not lower than 18 mEq/L, blood glucose normal to mildly elevated 2, 6
• Ketone bodies range 0.3-4 mmol/L with normal pH 6
• Up to 30% of first morning urine specimens show positive ketones even in healthy individuals during fasting 3, 1, 2

Blood in Urine Context

While the evidence provided focuses primarily on ketones, blood in urine combined with ketones in a diabetic patient heightens concern for severe metabolic decompensation and possible concurrent urinary tract infection, which is a common DKA precipitant. 2

Blood Ketone Action Thresholds

The American College of Clinical Endocrinologists recommends: 2

• <0.5 mmol/L: No intervention needed
• 0.5-1.5 mmol/L: Initiate sick-day rules (increase insulin, maintain hydration, monitor closely)
• ≥1.5 mmol/L: Seek immediate medical attention

Special Populations and Medications

SGLT2 Inhibitors

• These medications decrease the hyperglycemia that typically accompanies DKA, making diagnosis more challenging 2
• Can cause euglycemic DKA where glucose may be <250 mg/dL despite severe ketoacidosis 2
• Patients on these medications require immediate evaluation for pathological ketosis 1, 2

Pregnancy

• Positive ketone readings found in up to 30% of first morning urine specimens from pregnant women 3, 2
• Ketone testing is particularly important in pregnancy with pre-existing diabetes and gestational diabetes 3

Key Clinical Pearls

• Never rely on urine ketone testing alone for clinical decision-making in suspected DKA—blood beta-hydroxybutyrate is the gold standard 1, 2, 5
• Ketone testing materials should be available in office/clinic settings, but blood ketone methods are preferred over urine for diagnosing and monitoring ketoacidosis 3
• Type 1 diabetic patients should test for ketones during acute illness, stress, consistently elevated blood glucose (>300 mg/dL), or when symptoms like nausea, vomiting, or abdominal pain are present 3