What causes ketones in urine?

What Causes Ketones in Urine

Ketones appear in urine when your body breaks down fat for energy instead of glucose, occurring in both normal physiological states (fasting, pregnancy, low-carbohydrate diets) and pathological conditions (diabetic ketoacidosis, alcoholic ketoacidosis, insulin deficiency). 1

Normal Physiological Causes

• Insufficient caloric intake triggers ketone production as the body metabolizes fat stores when glucose availability is low 2
• Fasting or prolonged exercise activates lipid energy metabolism, producing ketones as an alternative fuel source, particularly important for brain function 3
• Pregnancy shows positive ketones in up to 30% of first morning urine specimens as a normal finding 2, 4
• Intentional carbohydrate restriction (ketogenic diets) induces nutritional ketosis even without caloric restriction, with ketone levels ranging from 0.3 to 4 mmol/L 4
• Neonatal period and infancy represent times when lipid energy metabolism is particularly active and ketosis develops readily 3

Pathological Causes in Diabetic Patients

• Absolute or relative insulin deficiency is the primary mechanism, causing increased ketone production from triglycerides and decreased utilization in the liver 1
• Diabetic ketoacidosis (DKA) represents a medical emergency where high levels of counterregulatory hormones (cortisol, epinephrine, glucagon, growth hormone) combined with insulin deficiency drive excessive ketone production 1
• SGLT2 inhibitor therapy increases the risk of ketoacidosis even with normal or near-normal blood glucose levels 5
• Inadequate insulin dosing or treatment discontinuation in type 1 diabetes leads to hyperglycemia and ketoacidosis 6

Other Pathological Causes

• Alcohol consumption combined with poor nutritional intake (alcoholic ketoacidosis) is a common non-diabetic cause of significant ketonuria 2
• Corticosteroid or growth hormone deficiency can trigger pathologic ketosis 3
• Salicylate intoxication may cause ketosis 3
• Inborn errors of metabolism represent rare causes of abnormal ketone production 3

Biochemical Mechanism

The principal ketone bodies—β-hydroxybutyrate (βOHB) and acetoacetate (AcAc)—are produced from free fatty acid oxidation in the liver 1. The equilibrium between these ketones shifts toward βOHB formation in conditions that increase hepatic mitochondrial NADH concentrations, including:

• Hypoxia 1
• Fasting 1
• Metabolic disorders including DKA 1
• Alcoholic ketoacidosis 1

Critical Clinical Distinctions

Physiological ketosis is characterized by ketone bodies ranging from 0.3 to 4 mmol/L, with normal pH, low but physiologically normal insulin levels, and normal blood glucose 4

Pathological ketosis (DKA) is characterized by low systemic pH, absent or severely deficient insulin, and very high ketone bodies (>7-8 mmol/L) 4

Important Testing Limitations

• Standard urine ketone tests using nitroprusside reagents only detect acetoacetate, not β-hydroxybutyrate, which is the predominant ketone body in most ketotic states 2, 5
• This creates a critical pitfall: urine tests may underestimate total ketone body concentration by missing βOHB, potentially providing misleading clinical information 1
• During DKA resolution, βOHB is oxidized to acetoacetate, so urine ketone tests might show increasing levels even as DKA is resolving 5
• False-positive results occur with highly colored urine or sulfhydryl drugs like captopril 1, 7
• False-negative results occur with prolonged air exposure of test strips or highly acidic urine 7

When to Seek Immediate Medical Evaluation

Seek emergency care if ketonuria is accompanied by:

• Persistent vomiting or inability to tolerate oral hydration 2
• Abdominal pain, nausea, or altered mental status 2
• Symptoms of hyperglycemia: increased thirst, frequent urination, fruity breath odor, drowsiness, flushed dry skin 6