What is the significance of ketones, protein, and bilirubin (bili) in urine?

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From the Guidelines

The presence of ketones, protein, and bilirubin in urine is a significant finding that requires immediate medical evaluation to determine the underlying cause and prevent potential complications, such as diabetic ketoacidosis, kidney damage, or liver dysfunction. Ketones in urine suggest that the body is burning fat for energy instead of glucose, which can occur during fasting, significant carbohydrate restriction, uncontrolled diabetes, or excessive alcohol consumption 1. Protein in urine (proteinuria) may indicate kidney damage or disease, as healthy kidneys typically don't allow protein to pass into urine 1. Bilirubin in urine points to possible liver dysfunction or bile duct obstruction, as this yellowish pigment should normally be processed by the liver and excreted in stool 1.

Some key points to consider:

  • Ketone testing is recommended for individuals prone to ketosis, such as those with type 1 diabetes, history of diabetic ketoacidosis, or treated with sodium-glucose transport protein 2 inhibitors, especially if they have unexplained hyperglycemia or symptoms of ketosis 1.
  • Proteinuria is optimally assessed by screening with automated dipstick urinalysis and then quantifying with a urine protein/creatinine ratio, with a ratio ≥30 mg/mmol (0.3 mg/mg) considered abnormal 1.
  • Bilirubin levels can indicate liver dysfunction or bile duct obstruction, and elevations in either unconjugated or conjugated fractions can lead to a rise in the measured bilirubin concentration 1.

It is essential to seek medical attention promptly if ketones, protein, and bilirubin are present in urine, especially if accompanied by symptoms like fatigue, abdominal pain, dark urine, or swelling. The doctor will likely order additional tests, including comprehensive blood work to check liver and kidney function, blood glucose levels, and possibly imaging studies. Treatment will depend on the underlying cause, ranging from dietary modifications for ketones related to low-carbohydrate diets to specific medications for liver or kidney conditions. While waiting for medical evaluation, it is crucial to ensure adequate hydration and avoid fasting or extreme diets that might worsen these abnormalities.

From the Research

Ketones in Urine

  • The presence of high urinary ketoacids is one of the criteria for diagnosing diabetic ketoacidosis (DKA) 2, 3
  • Elevated serum or urine ketones are traditionally used to diagnose DKA, with hyperglycemia and metabolic acidosis being the other two components of the triad 3

Protein in Urine

  • There is no direct mention of protein in urine in the provided studies as a diagnostic criterion for DKA or any other condition related to ketones, protein, and bilirubin in urine

Bili in Urine

  • There is no mention of bilirubin in urine in the provided studies as a diagnostic criterion for DKA or any other condition related to ketones, protein, and bilirubin in urine

Diagnostic Criteria and Tests

  • DKA is diagnosed by the presence of hyperglycemia, metabolic acidosis, and elevated serum or urine ketones 3
  • Additional tests such as electrolytes, phosphate, blood urea nitrogen, creatinine, urinalysis, complete blood cell count with differential, A1C, and electrocardiography should be evaluated for all patients diagnosed with DKA 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diabetic ketoacidosis.

Nature reviews. Disease primers, 2020

Research

Diabetic Ketoacidosis: Evaluation and Treatment.

American family physician, 2024

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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