Should I treat a patient with symptoms and urinalysis results showing ketone trace and protein trace, but otherwise negative, including complete blood count (CBC), blood urea nitrogen (BUN), and electrolyte panel?

Treatment Decision for Trace Ketones and Trace Protein with Symptoms

You should treat this patient if they have symptoms suggestive of diabetic ketoacidosis (DKA) or metabolic decompensation, regardless of the "trace" findings, by obtaining immediate blood glucose, serum ketones (preferably β-hydroxybutyrate), arterial blood gas, comprehensive metabolic panel with anion gap, and serum osmolality to determine if DKA or hyperosmolar hyperglycemic state is present. 1

Critical Initial Assessment

The presence of any urine ketones in a symptomatic patient is highly sensitive for DKA or significant ketosis and should never be dismissed as clinically insignificant. 2 The key issue is that trace findings on urinalysis can represent early or evolving metabolic crisis, particularly if the patient has symptoms.

Symptoms That Mandate Immediate Workup

You must obtain comprehensive laboratory evaluation if the patient presents with: 1, 3

• Nausea, vomiting, or abdominal pain (present in 32-46% of DKA cases)
• Dyspnea or increased respiratory effort (57% of cases)
• Fatigue or altered mental status (62% of cases)
• Polyuria with polydipsia (98% of cases)
• Recent illness, decreased oral intake, or dehydration

Essential Laboratory Workup

Immediate tests required: 1

• Arterial blood gas to document pH (DKA if pH <7.3)
• Serum β-hydroxybutyrate (preferred over urine ketones, as it's the predominant ketone in DKA) 1
• Comprehensive metabolic panel with calculated anion gap
• Serum glucose (though DKA can occur with glucose >250 mg/dL, euglycemic DKA exists)
• Serum osmolality using formula: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 1
• Complete blood count to evaluate for infection as precipitating factor 1

Why Urine Ketones Alone Are Insufficient

Standard urine dipstick tests only measure acetoacetate and acetone, not β-hydroxybutyrate, which is the strongest and most prevalent ketone in DKA. 2 During early DKA or in conditions that alter the redox state (hypoxia, fasting, alcoholic ketoacidosis), β-hydroxybutyrate predominates, meaning urine dipstick can significantly underestimate total ketone burden. 2

Clinical Decision Algorithm

If symptoms present + trace ketones:

1. Obtain serum glucose immediately - If >250 mg/dL with symptoms, presume DKA until proven otherwise 3
2. Check serum β-hydroxybutyrate and arterial blood gas - pH <7.3 and bicarbonate ≤15-18 mEq/L confirms DKA 1
3. Calculate anion gap - Elevated anion gap metabolic acidosis supports DKA 1
4. Assess for precipitating factors - Infection, medication non-compliance, SGLT2 inhibitor use 4, 5

If glucose >600 mg/dL with minimal ketones:

• Consider hyperosmolar hyperglycemic state (HHS): pH >7.3, bicarbonate >15 mEq/L, effective osmolality >320 mOsm/kg 1

Critical Pitfall: Euglycemic DKA

Do not be falsely reassured by normal or mildly elevated glucose. 4, 5 Euglycemic DKA (eDKA) can occur with:

• SGLT2 inhibitor use (dapagliflozin, empagliflozin, canagliflozin) - can cause eDKA even 8-11 days after last dose 4
• Decreased carbohydrate intake or fasting
• Recent surgery or severe illness
• Pregnancy

In eDKA, glucose may be <200 mg/dL but severe ketoacidosis is still present, making diagnosis challenging and easily missed. 4, 5

Regarding Trace Protein

Trace proteinuria in this context is likely secondary to:

• Dehydration/concentrated urine (most common with DKA presentation) 6
• Underlying diabetic nephropathy (if patient has diabetes)
• Acute kidney injury from volume depletion 4

The trace protein finding should not distract from the more urgent concern of ketones with symptoms. However, if DKA/HHS is ruled out, persistent proteinuria requires follow-up evaluation. 6

Treatment Initiation

If DKA confirmed (pH <7.3, bicarbonate ≤18 mEq/L, positive ketones): 2, 1

• Intravenous fluid resuscitation (initial bolus 15-20 mL/kg/hour of 0.9% saline)
• Insulin infusion at 0.1 U/kg/hour (but hold if K+ <3.3 mEq/L until potassium repleted) 1
• Potassium replacement (20-40 mEq/L in IV fluids once K+ known and renal function confirmed) 1
• Monitor glucose, electrolytes, pH every 2-4 hours 1

Bottom Line

Trace ketones with symptoms is not a benign finding. The "trace" designation on urinalysis reflects only acetoacetate/acetone and may grossly underestimate total ketone burden. 2 Any symptomatic patient with ketonuria requires immediate comprehensive metabolic evaluation to exclude DKA or HHS, both of which are medical emergencies with 1-5% mortality if untreated. 3