What causes bilirubinuria?

What Causes Bilirubin in the Urine

Bilirubin in the urine (bilirubinuria) occurs exclusively when conjugated (water-soluble) bilirubin is elevated in the blood, indicating either liver parenchymal disease or biliary obstruction. 1

Mechanism of Bilirubinuria

• Only conjugated bilirubin appears in urine because it is water-soluble and small enough to be filtered by the kidneys, whereas unconjugated bilirubin is bound to albumin and cannot pass through the glomerular filter 1
• The presence of bilirubinuria specifically indicates conjugated hyperbilirubinemia and requires evaluation for underlying hepatobiliary disease 1

Primary Causes of Bilirubinuria

Hepatocellular Disease (Parenchymal Liver Injury)

The liver is damaged but can still conjugate bilirubin, which then leaks into the bloodstream:

• Viral hepatitis (hepatitis A, B, C, D, or E) 2, 1
• Alcoholic liver disease - a leading cause of jaundice in the United States (16% of new-onset jaundice cases) 2, 1
• Drug-induced liver injury or toxic reactions to medications/herbal supplements 2, 1
• Autoimmune hepatitis 2, 1
• Sepsis/shock - the most common cause of new-onset jaundice in U.S. studies (22% of cases) 2
• Cirrhosis with decompensation (20.5% of new-onset jaundice) 2

Cholestatic/Obstructive Causes

Conjugated bilirubin cannot be excreted into bile, causing backup into the bloodstream:

• Common bile duct obstruction by gallstones (choledocholithiasis) - accounts for 13-14% of jaundice cases 2, 1
• Malignancy causing biliary obstruction (pancreatic cancer, cholangiocarcinoma, ampullary tumors) - the most common cause of severe jaundice in European studies 2, 1
• Primary biliary cholangitis 1
• Primary sclerosing cholangitis 1
• Medication-induced cholestasis 1
• Biliary strictures 1

Clinical Differentiation

The pattern of liver enzyme elevation helps distinguish the underlying cause: 2

• Hepatocellular pattern: Predominantly elevated aminotransferases (ALT/AST) with conjugated hyperbilirubinemia suggests hepatitis, alcoholic liver disease, drug-induced liver injury, or sepsis 2
• Cholestatic pattern: Predominantly elevated alkaline phosphatase and GGT with conjugated hyperbilirubinemia suggests bile duct obstruction by stones or tumor 2

Important Caveats

• Gilbert's syndrome does NOT cause bilirubinuria because it involves unconjugated hyperbilirubinemia only; if bilirubinuria is present, Gilbert's syndrome is excluded as the cause 2
• Hemolysis does NOT cause bilirubinuria because it produces unconjugated hyperbilirubinemia 2
• In neonates and infants, conjugated bilirubin >25 μmol/L with bilirubinuria requires urgent pediatric referral for possible biliary atresia or other serious liver disease 2, 1
• The geographic location, hospital setting (tertiary vs. community), and patient demographics significantly influence which causes are most common 2