What causes high ketones in urine?

Causes of High Ketones in Urine

High ketones in urine are primarily caused by insulin deficiency leading to increased fat metabolism, which occurs in diabetic ketoacidosis, starvation, prolonged fasting, low-carbohydrate diets, pregnancy, and during intense exercise. 1

Physiological Causes of Ketonuria

• Normal fasting state: Ketones are normally present in urine but usually below detectable levels. However, positive ketone readings can be found in:

  • Normal individuals during fasting
  • Up to 30% of first morning urine specimens from pregnant women 2
  • During prolonged exercise when glucose availability is limited 3

• Low-carbohydrate states: When the body has limited access to carbohydrates, it shifts to fat metabolism, producing ketones:

  • Prolonged fasting or starvation
  • Low-carbohydrate/ketogenic diets
  • Malnutrition

Pathological Causes of Ketonuria

Diabetes-Related Causes

1. Diabetic Ketoacidosis (DKA):

   • Most serious cause of elevated ketones
   • Results from insulin deficiency with elevated counterregulatory hormones 1
   • Diagnostic criteria: hyperglycemia (blood glucose >250 mg/dL), metabolic acidosis (pH <7.3, bicarbonate <15 mEq/L), and elevated ketones 1
   • Common precipitating factors:
     • Omitting insulin or taking less than prescribed
     • Significant dietary indiscretion
     • Infection, fever, or other stressful situations 4

2. Euglycemic DKA:

   • Ketoacidosis with relatively normal blood glucose (<250 mg/dL)
   • Common with SGLT2 inhibitor use
   • Also seen in pregnancy, starvation, alcohol use, and chronic liver disease 5

Other Medical Conditions

• Alcoholic ketoacidosis: Occurs after binge drinking followed by reduced food intake
• Starvation ketosis: Distinguished from DKA by serum bicarbonate levels usually not lower than 18 mEq/L 1
• Pregnancy-related: Accelerated starvation ketosis can occur in pregnancy
• Certain medications: SGLT2 inhibitors significantly increase risk of ketosis regardless of glucose levels 1

Risk Factors for Developing Significant Ketonuria

• Type 1 diabetes (highest risk)
• Absolute insulin deficiency
• Younger age
• Prior history of hyperglycemic crises
• Existing diabetes complications
• Behavioral health conditions
• SGLT2 inhibitor use
• Pregnancy 1

False Results in Ketone Testing

• False-positive results:

  • Presence of sulfhydryl drugs (including the antihypertensive drug captopril) 2
  • Highly pigmented urine
  • Certain medications

• False-negative results:

  • Test strips exposed to air for extended periods
  • Highly acidic urine (e.g., after large intakes of ascorbic acid) 2
  • Using nitroprusside-based tests when β-hydroxybutyrate is the predominant ketone 3

Clinical Implications and Monitoring

• Ketone testing is essential for:

  • Type 1 diabetic patients
  • Pregnancy with pre-existing diabetes
  • Gestational diabetes 2

• Patients should test for ketones during:

  • Acute illness or stress
  • When blood glucose levels are consistently elevated (>300 mg/dL)
  • During pregnancy
  • When symptoms of ketoacidosis are present (nausea, vomiting, abdominal pain) 2

• Blood ketone testing (measuring β-hydroxybutyrate) is preferred over urine ketone testing for diagnosing and monitoring ketoacidosis 2, 1

• Early symptoms of DKA include:

  • Drowsiness, flushed face
  • Thirst, loss of appetite
  • Fruity odor on breath 4

Remember that while urine ketone tests are widely available, they only detect acetoacetate and acetone, not β-hydroxybutyrate (the predominant ketone in DKA). This limitation can lead to underestimation of ketone levels, especially during early treatment of DKA when β-hydroxybutyrate is being converted to acetoacetate 1, 6.