What are the potential causes of ketones and hematuria (blood in urine) in a patient?

Conditions Causing Ketones and Blood in Urine

The simultaneous presence of ketones and hematuria most commonly indicates diabetic ketoacidosis (DKA) with concurrent urinary tract infection, as infection precipitates approximately 50% of DKA cases and urinary tract infections are among the most frequent bacterial triggers. 1, 2

Primary Diagnostic Consideration: Diabetic Ketoacidosis with Infection

DKA with urinary tract infection represents the most critical diagnosis to rule out immediately, as this combination carries higher mortality than DKA alone. 2 The diagnostic approach requires:

• Immediate blood glucose measurement to distinguish DKA from benign starvation ketosis—glucose >250 mg/dL indicates a medical emergency requiring urgent DKA evaluation. 3
• Complete DKA diagnostic criteria: plasma glucose >250 mg/dL, arterial pH <7.30, serum bicarbonate <15 mEq/L, positive ketones, and anion gap >10 mEq/L. 1, 3
• Blood beta-hydroxybutyrate measurement is strongly preferred over urine testing for all clinical decision-making, as urine dipsticks only detect acetoacetate and significantly underestimate total ketone concentration. 3, 4

Infection as DKA Precipitant

Infection is the most common precipitating factor for DKA, with urinary tract infections being particularly frequent. 1 The presence of hematuria alongside ketones should trigger:

• Bacterial cultures of urine, blood, and other sites as indicated. 1
• Recognition that patients with DKA and infection can be normothermic or even hypothermic due to peripheral vasodilation. 1
• Understanding that hypothermia, if present, is a poor prognostic sign. 1

Alternative Causes of Combined Ketones and Hematuria

Euglycemic DKA with Infection

SGLT2 inhibitors can cause euglycemic DKA where glucose may be <250 mg/dL despite severe ketoacidosis, making diagnosis more challenging. 3 This is critical because:

• Blood ketone action thresholds: <0.5 mmol/L (no intervention), 0.5-1.5 mmol/L (initiate sick-day rules), ≥1.5 mmol/L (immediate medical attention). 3
• Patients on SGLT2 inhibitors with any ketones require immediate evaluation for pathological ketosis. 3, 4

Starvation Ketosis with Unrelated Hematuria

Starvation ketosis occurs from reduced caloric intake and is characterized by:

• Normal or low blood glucose levels. 3
• Serum bicarbonate usually not lower than 18 mEq/L. 1, 3
• Blood ketones ranging 0.3-4 mmol/L. 3

In this scenario, hematuria would be from a separate cause (urinary tract infection, nephrolithiasis, glomerulonephritis, trauma, malignancy). 4

Alcoholic Ketoacidosis with Concurrent Urinary Pathology

Alcoholic ketoacidosis presents with positive urine ketones but hyperglycemia is not usually present. 3 The hematuria would represent a separate pathology, potentially related to:

• Alcohol-related trauma. 1
• Concurrent urinary tract infection.
• Alcohol-induced coagulopathy causing bleeding.

Critical Pitfalls to Avoid

Do not rely on urine ketone testing alone—the nitroprusside method (standard urine dipstick) does not measure beta-hydroxybutyrate, the predominant ketone body in DKA. 3, 5 This can lead to:

• Underestimation of ketone severity during active DKA. 3, 6
• False reassurance as DKA resolves, since urine acetoacetate may increase even as blood beta-hydroxybutyrate decreases with treatment. 6

False-positive ketones can occur with sulfhydryl drugs like captopril. 4, 7

False-negative ketone results occur with prolonged air exposure of test strips or highly acidic urine. 4, 7

Algorithmic Approach

1. Check blood glucose immediately: >250 mg/dL = medical emergency. 3
2. If glucose elevated: Obtain blood beta-hydroxybutyrate, arterial blood gas, electrolytes with anion gap, urinalysis with culture. 1, 3
3. If DKA criteria met: Initiate treatment with isotonic saline 15-20 ml/kg/h, insulin therapy, and appropriate antibiotics if infection suspected. 1
4. If glucose normal/low: Consider starvation ketosis (benign) versus alcoholic ketoacidosis, and evaluate hematuria as separate entity. 3
5. High-risk patients (type 1 diabetes, prior DKA, on SGLT2 inhibitors) require immediate evaluation regardless of glucose level. 3