Reference Range

Blood urea nitrogen (BUN) testing is commonly part of the basic metabolic panel (BMP) or comprehensive metabolic panel (CMP), which is commonly obtained as part of a routine medical examination. It is also obtained in patients in emergency or urgent care settings, as it can provide valuable information that may provide clues to various clinical presentations that may be caused by chemical imbalances in the body that require prompt and immediate attention.

Urea production occurs primarily in the liver (urea cycle, also referred to as the ornithine cycle) and is regulated by N-acetylglutamate. Urea is found dissolved in blood and is excreted by the renal tubules. In addition, a small amount of urea is also excreted in sweat. Therefore, the BUN level may reflect functioning of the liver and/or kidneys.

The reference ranges for the BUN levels are as follows^[1]:

Adult: 10-20 mg/dL or 3.6-7.1 mmol/L (SI units)
Elderly: May be slightly raised beyond adult levels
Child: 5-18 mg/dL
Infant: 5-18 mg/dL
Newborn: 3-12 mg/dL
Cord: 21-40 mg/dL

Possible critical value^[1]:

>100 mg/dL (indicates seriously impaired renal function)

Interpretation

As with serum creatinine, the BUN level varies inversely with the glomerular filtration rate (GFR).^[2]However, certain conditions can result in elevated BUN levels that may not truly reflect renal functioning.^[3]

The rate of urea production is not constant. It is elevated in those who consume a diet fairly high in protein and in conditions characterized by enhanced tissue breakdown (eg, hemorrhage, trauma, glucocorticoid therapy). Certain antibiotics, such as tetracyclines, may interfere with protein synthesis and tend to be catabolic, thereby also increasing BUN levels. On the other hand, a low-protein diet or liver disease can decrease the BUN level without affecting GFR or renal function.^[4]

Liver disease may be associated with near-normal values of both BUN (due to decreased urea production) and serum creatinine (due to muscle wasting), despite a significant decline in renal function manifested by decreased GFR.^[5]

Approximately 40%-50% of the filtered urea undergoes passive reabsorption in the proximal tubule. In states of intravascular volume depletion, proximal sodium and water reabsorption increases, coupled with a parallel increase in the reabsorption of urea. This results in a disproportionate rise in BUN levels relative to any change in serum creatinine levels. This elevation in the BUN-to-creatinine ratio is one of the laboratory indicators of decreased renal perfusion. The ratio is indicative of prerenal injury when the BUN-to-creatinine ratio is greater than 20.

The ratio is may also be useful for diagnosing gastrointestinal bleeding in some patients who do not present with overt blood loss. In children, a BUN-to-creatinine ratio of 30 or greater has a sensitivity of 68.8% and a specificity of 98% for upper gastrointestinal bleeding.

The value of this ratio is limited by other factors that can affect BUN independently, such as various drugs.

Drugs that can increase BUN levels include the following:

Allopurinol
Aminoglycoside antibiotics
Amphotericin B
Aspirin (high doses)
Bacitracin
Carbamazepine
Cephalosporins
Chloral hydrate
Cisplatin
Colistin
Furosemide
Guanethidine
Indomethacin
Methicillin
Methotrexate
Methyldopa
Neomycin
Penicillamine
Polymyxin B
Probenecid
Propranolol
Rifampin
Spironolactone
Tetracyclines
Thiazide diuretics
Triamterene
Vancomycin

The following drugs can decrease BUN levels:

Chloramphenicol
Streptomycin

Another use for BUN assessment is in calculating the urea reduction ratio (URR), with the following formula:

URR = 1 - (postdialysis BUN level/predialysis BUN level)

Because of its ease of calculation, the URR is frequently used in epidemiologic studies. One study evaluated the correlation between various demographic characteristics and a URR of less than 65%, a hemodialysis dose that is less than the currently recommended minimum amount.^[6]

BUN levels tend to increase with age. In infants and children, BUN levels are about two thirds of those found in healthy young adults, while levels in adults older than 60 years are slightly higher than those in younger adults. They are also slightly higher in males than in females, probably reflective of the lower muscle mass in the latter. During pregnancy, physiologic changes in blood flow can also lower BUN levels.

Methodology

BUN testing was originally performed via flame photometry. Currently, chemical colorimetric tests are more widely used, such as the diacetyl monoxime method, urograph method, and the modified Berthelot enzymatic method.

A 5-mL blood sample is obtained and placed in a green-top tube, which is then gently inverted several times, with care to avoid agitation in order to prevent RBC hemolysis). The specimen is kept cool, as elevated temperatures can alter the result. No specific condition exists under which the specimen should be drawn.

Description

In humans, some of the amino acids derived from ingested food that are not used for protein synthesis are oxidized, thereby yielding urea and carbon dioxide as alternative sources of energy.^[7]

In the United States, blood urea nitrogen (BUN) is measured in mg/dL. To convert BUN to a concentration in mmol/L (SI units), multiply by 0.357 ([10 dL/1 L]/[28 mg of N/mmol of urea] = 0.357).

Indications/Applications

BUN testing is commonly part of the BMP or CMP, which is commonly obtained as part of a routine medical examination. It is also obtained in patients in emergency or urgent care settings, as it can provide valuable information that may provide clues to various clinical presentations that may be caused by chemical imbalances in the body that require prompt and immediate attention.