Increased BUN is most often associated with significant hypovolemia, renal disease, or urinary obstruction and can be found in conjunction with other markers of decreased glomerular filtration (eg, increased creatinine). Clinical signs are associated with underlying pathology. BUN can also be elevated in apparently healthy patients.
Ask the Expert: What are the possible explanations for increased BUN in dogs with no other laboratory abnormalities or clinical signs?
High-Protein Diet
BUN is produced by the liver from dietary and recycled endogenous proteins; therefore, diets higher in protein may result in higher BUN. The effect of dietary protein is likely minimal in otherwise healthy dogs fed a commercial diet but can be a differential for mildly increased BUN in apparently healthy dogs fed diets with unusually high protein levels.1,2 Prerenal azotemia or underlying renal disease may exacerbate the effects of high-protein diets on BUN (see Prerenal Azotemia).3
GI Hemorrhage
Hemorrhage is a pathologic condition associated with GI ulceration (eg, from NSAID use), parasitism, or neoplasia. Although hemorrhage into the upper GI tract can cause increased BUN,4 this finding is unpredictable because of accompanying anorexia and variable bleeding locations.5 Hemorrhage-induced increases in BUN are generally thought to result from digestion of blood that functions as a high-protein meal. Dogs may have accompanying GI signs (eg, vomiting, hematochezia, melena) or be clinically normal depending on the underlying cause and degree of hemorrhage. Other laboratory abnormalities associated with GI hemorrhage may include regenerative anemia (decreased hemoglobin, hematocrit, and/or RBC count with increased reticulocyte count) or microcytic hypochromic anemia (indicating iron deficiency), depending on the severity and chronicity of bleeding. If GI hemorrhage is suspected but not grossly visible as hematochezia or melena, a fecal occult blood test can be performed to screen for smaller quantities of blood; however, findings should not be considered definitive alone, as both false-positive (from diet interference) and false-negative (from intermittent bleeding) results are possible.6
Prerenal Azotemia
Early or mild cases of prerenal azotemia are usually associated with clinical signs and increased creatinine but can be subclinical with increased BUN alone because BUN undergoes greater resorption from renal tubules when the tubular flow rate is decreased.4 Mild dehydration is the most likely cause.4 Occult cardiac disease or hypoadrenocorticism are also possible but are more likely to be associated with clinical signs or other laboratory abnormalities.
Renal Azotemia
Like prerenal azotemia, renal disease is often associated with clinical signs and other biochemical markers of decreased renal function; however, early renal disease can be found in apparently healthy dogs, and nonrenal factors (eg, reduced muscle mass) can lower creatinine, complicating interpretation. Evaluation of symmetric dimethylarginine (SDMA) may be useful in these cases, as SDMA is also a marker of decreased glomerular filtration. SDMA can indicate renal disease earlier than BUN and creatinine and may have fewer nonrenal influences.7 If SDMA measurement is not available, repeat blood work may be needed to evaluate BUN and creatinine over time.
Artifact
Measurement error due to improper sample storage or interference from lipemia, hemolysis, or icterus should be considered if a result does not match the patient’s clinical presentation or other laboratory results; however, BUN is a relatively stable analyte when samples are refrigerated or frozen, and interferences with measurement are rare.4 BUN may increase slightly above baseline after feeding but is expected to stay within the reference interval.1
Breed & Age
Breed variations can affect interpretation of certain analytes, but no definitive differences have been noted for BUN. Puppies <6 months of age tend to have lower BUN than adults; most results, however, are within adult reference intervals.8
Normal Variation
Most reference intervals encompass 95% of healthy patients; low numbers of healthy patients therefore have transient or persistent BUN results at the upper end of or slightly above the reference interval. Mildly increased BUN in a dog with no clinical signs or relevant conditions (as mentioned in this article) may represent a normal value for that dog. In these patients, comparing current BUN results with previous results may be more informative than comparisons with general population reference intervals.