Blood Urea Nitrogen (BUN) Concentration in Dogs

Jennifer A. McKee, DVM; Kenneth S. Latimer, DVM, PhD; Bruce E. LeRoy, DVM, PhD

Class of 2004 (McKee), Department of Pathology (Latimer, LeRoy), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602

Introduction

The blood urea nitrogen (BUN) test is a measurement of the amount of urea that has been passively absorbed into the vascular system. The majority of urea (Fig. 1) is synthesized from ammonia by the liver during the hepatic urea cycle.² Urea is freely filtered by the glomeruli and partially passively resorbed as filtrate transverses the renal tubules.⁵ The kidneys excrete the majority of urea. Reabsorption of urea is inversely related to urine flow rate, as well as many other factors.

Figure 1. Molecular structure of urea (H2NCONH2).

Determination of BUN

In the past, BUN was measured in whole blood. Today, BUN concentration is determined by analysis of serum or plasma.⁵ Blood urea nitrogen, serum urea nitrogen, and urea nitrogen measurements are equivalent due to the fact that urea diffuses quickly and passively through the total body water compartment (diffusion time of approximately 90 minutes).²

Blood urea nitrogen is most accurately measured by a colorimetric process, which gives a quantitative test result.² It can also be measured by the diacetylmonoxime method, but the test results are less accurate. The reference interval for BUN in the dog ranges from 8 to 28 mg/dl.²

Clinical Importance of Measuring BUN

Blood urea nitrogen (BUN) is typically measured to assess kidney function; however, there are many different metabolic processes and diseases that alter BUN concentration.

The processes that alter BUN can be broken into three major categories including pre-renal, renal, and post-renal abnormalities (Table 1).^1,2

BUN is often considered an insensitive measure of kidney function since an increase in BUN concentration occurs only after at least 65%-75% of the functional kidney mass has been lost (Fig. 2).⁴ Measuring the urine specific gravity can help differentiate between pre-renal and renal causes of azotemia (increased concentration of urea or other nonprotein nitrogen compounds in the blood). In pre-renal azotemia, renal function is not altered. The kidneys are able to concentrate urine, resulting in a urine specific gravity of > 1.030 in dogs and > 1.035 in cats. With renal azotemia the urine specific gravity will be lower than these values, and may be isosthenuric (1.008-1.012) because the kidneys have lost the ability to concentrate the urine. Creatinine is another nitrogenous substance in the blood whose measurement also may assist in differentiating the causes of azotemia.

Figure 2. Longitudinal cut sections of a kidney (left) from a dog with end stage renal disease compared to a normal kidney (right). The diseased kidney has an undulating surface, variable width of the cortex, and a lighter color. The normal kidney has a smooth surface, regular cortical width, and a dark mahogany color (Courtesy of Noah's Arkive, The University of Georgia).

Table 1. Major causes of increased and decreased blood urea nitrogen concentrations.

Common Mechanisms for Increased BUN Concentration

Upper gastrointestinal hemorrhage - Increased BUN concentration due to upper gastrointestinal tract hemorrhage is thought to be caused by increased protein catabolism as well as blood volume loss.³ A retrospective study by Prause et. al. determined that patients with clinical signs of upper gastrointestinal tract hemorrhage had significantly increased BUN concentration and BUN/creatinine ratio.

Post renal obstruction - Vasoactive substances such as prostaglandins and angiotensin are released during obstruction of the urinary system. These substances cause constriction of the glomerular arterioles, reducing the blood flow and decreasing the glomerular filtration rate (GFR). In turn, the decreased GFR prevents clearance of both BUN and creatinine, causing increased concentrations of these substances in the blood.⁴

Common Mechanisms for Decreased BUN Concentration

The basic mechanism causing a decreased BUN concentration is a decrease in protein catabolism or an inability to synthesize urea from ammonia.

Hepatic insufficiency - Hepatic insufficiency causes a decreased BUN concentration due to destruction of functional hepatic mass and decreased urea output from the hepatic urea cycle.²

Conclusion

BUN concentration is most often measured to assess kidney function. It is important to realize that many different disease conditions alter BUN concentration but may or may not alter renal function. Therefore, BUN concentration should be compared with creatinine concentration and urine specific gravity to properly evaluate kidney function.

References

1. Finco DR: Kidney function. In: Kaneko JJ, Harvey JW, Bruss ML (eds): Clinical Biochemsitry of Domestic Animals, 5th ed. San Diego, Academic Press, 1997, pp. 468-472.

2. Gregory CR: Urinary System. In: Latimer KS, Mahaffey EA, Prasse KW: Duncan and Prasse’s Veterinary Laboratory Medicine: Clinical Pathology, 4th ed. Ames, Iowa State Press, 2003, pp 250-53 & 341.

3. Prause LC, Grauer GF: Association of gastrointestinal hemorrhage with increased blood urea nitrogen and BUN / creatinine ratio in dogs: A literature review and retrospective study. Vet Clin Pathol 27:107-110, 1998.

4. Stockham SL, Scott MA: Fundamentals of Veterinary Clinical Pathology. Ames, Iowa State Press, 2002, pp. 289-294.

5. Osborne CA, Finco DR (eds): Canine and Feline Nephrology and Urology. Baltimore, Williams & Wilkins, 1995, pp. 217-218.

Acknowledgement

The image of the urea molecular model above (background slightly modified) is from the web site of Dr. Suzanne W. Slayden, Chemistry Department, George Mason University at http://classweb.gmu.edu/sslayden/graphics/urea.gif.

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