What does the presence of ketones and glucose in urine indicate?

Ketones and Glucose in Urine: Clinical Significance and Implications

The presence of both ketones and glucose in urine strongly suggests diabetic ketoacidosis (DKA) or impending DKA, which requires immediate medical attention. 1

Understanding Urinary Glucose

Glucose in urine (glycosuria) indicates:

• Blood glucose levels exceeding the renal threshold (typically >180 mg/dL)
• Hyperglycemia, most commonly due to diabetes mellitus
• Possible renal tubular dysfunction in some cases

While urine glucose testing was historically used for diabetes monitoring, it has been largely replaced by self-monitoring of blood glucose (SMBG) due to significant limitations 2:

• Reflects average blood glucose since last void rather than current levels
• Affected by hydration status and renal threshold variations
• Provides delayed information compared to direct blood glucose measurement

Understanding Urinary Ketones

Ketones in urine (ketonuria) indicates:

• Increased fat metabolism due to carbohydrate deficiency or inability to use glucose
• Potential insulin deficiency or insulin resistance
• Possible metabolic stress

Ketone bodies detected in urine include:

• Acetoacetate and acetone (detected by nitroprusside-based urine dipsticks)
• β-hydroxybutyrate (BHB) is NOT detected by standard urine dipstick tests but is the predominant ketone in DKA 1

Clinical Significance of Combined Findings

When both glucose and ketones appear in urine, consider:

1. Diabetic Ketoacidosis (DKA)

   • Most common and serious cause
   • Requires immediate treatment
   • Can occur in both type 1 and type 2 diabetes
   • May present with normal or only mildly elevated blood glucose in euglycemic DKA (particularly with SGLT2 inhibitor use) 3

2. Poorly Controlled Diabetes

   • Especially during illness, stress, or missed insulin doses
   • May represent impending DKA if not addressed

3. Starvation Ketosis

   • Less common when glucose is also present
   • Usually mild ketosis without significant acidosis

4. Pregnancy

   • Up to 30% of pregnant women may have physiologic ketonuria in morning specimens 1
   • Requires careful monitoring in women with pre-existing or gestational diabetes

Important Diagnostic Considerations

1. Urine ketone limitations:

   • Urine ketone tests using nitroprusside reagents only detect acetoacetate and acetone, not BHB (the predominant ketone in DKA) 1, 4
   • False-positive results can occur with certain sulfhydryl drugs (e.g., captopril) 2
   • False-negative readings may occur with aged test strips or highly acidic urine 2

2. Superior testing methods:

   • Blood ketone testing that quantifies β-hydroxybutyrate is preferred for diagnosing and monitoring ketoacidosis 2, 1
   • During DKA resolution, urine ketones may paradoxically increase as BHB converts to acetoacetate, creating a misleading impression of worsening ketosis 4

3. Screening value:

   • Despite limitations, urine ketone testing has high sensitivity (99%) and negative predictive value (100%) for excluding DKA in hyperglycemic patients 5
   • However, specificity is lower (69%), meaning positive results require confirmation 5

Clinical Management Algorithm

When ketones and glucose are detected in urine:

1. Immediate assessment:

   • Check blood glucose, blood ketones (BHB if available), electrolytes, and acid-base status
   • Calculate anion gap: [Na⁺] - ([Cl⁻] + [HCO₃⁻]) (>12 suggests metabolic acidosis) 1

2. If DKA is confirmed or suspected:

   • Initiate fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 ml/kg/h initially
   • Begin insulin therapy after initial fluid resuscitation
   • Monitor glucose, electrolytes, and acid-base status frequently 1

3. For non-emergency situations:

   • Increase fluid intake
   • Adjust insulin or diabetes medications as needed
   • Monitor blood glucose and ketones more frequently
   • Implement sick day management if applicable

Special Considerations

1. SGLT2 inhibitors:

   • Can cause euglycemic DKA (ketoacidosis with normal or only slightly elevated blood glucose)
   • Patients using these medications should measure ketones during any illness regardless of glucose levels 1, 3

2. Hypoalbuminemia:

   • Low serum albumin is associated with increased ketosis risk in hospitalized patients with type 2 diabetes 6
   • Consider more vigilant monitoring in these patients

3. Pregnancy:

   • Ketone testing is crucial during pregnancy with pre-existing or gestational diabetes
   • Morning ketonuria may be physiologic but should not be ignored in diabetic patients 1

4. Chronic hyperglycemia:

   • Elevated HbA1c may indicate long-standing undiagnosed diabetes even when presenting symptoms are attributed to other conditions 7