Blood Urea Nitrogen, BUN, or Urea Nitrogen (BUN/Creatinine ratio)

Sample

1. This is done on the serum of the patient.
2. No special preparation is needed.

Precautions

1. If there is Fluoride that will inhibit Urease reaction.
2. Avoid hemolysis.
3. Protein intake will affect BUN. A low protein diet will give low BUN.
4. A high protein diet or nasogastric tubing will increase BUN.
5. Keep in mind muscle mass which is more in males than females and children.
6. Overhydrated patients will dilute the BUN and gives a lower value.
7. The dehydrated patient will concentrate BUN and gives high value.
8. GI bleeding can cause an increase in BUN level.
9. Advanced pregnancy may increase the BUN level.
10. Drugs increasing the BUN level are cephalosporin, indomethacin, gentamicin, polymyxin B, rifampicin, bacitracin, neomycin, tetracycline, thiazide diuretics, and aspirin.
11. There are drugs that decrease the BUN level are streptomycin and chloramphenicol.

Indication

1. To assess renal function.
2. As a routine test in the patient with dialysis.
3. To assess liver function.
4. This may be part of the routine test.
5. In patients:
   1. Has nonspecific symptoms.
   2. During the hospital stay.
   3. Prior to some drug therapy.
   4. Acutely ill patients admitted in an emergency.

Pathophysiology

1. Blood urea molecule: O = C = ( NH2 )2 .
2. Urease enzyme can split urea into ammonia and carbon dioxide.

The chemical action of the urease enzyme

3. The molecular weight of urea = 60 grams
   1. Each molecule contains nitrogen = 28 grams. This is called blood urea nitrogen (BUN).
   2. While in the SI unit this is meaningless because it is reported as mmol/L.
   3. The serum concentration of 28 mg/dL of urea – nitrogen is equivalent to 60 mg/dL of urea or 10 mmol/L of urea or urea-nitrogen in SI units.
4. Proteins cannot be stored in the body when these are in excess then surplus amino acids are catabolized for energy.
   1.  Breakdown of the proteins and nucleic acid gives rise to a non-protein nitrogenous compound in the blood and these are urea, amino acids, urates, ammonia, and creatinine.
   2. Amino acids are converted into ammonia, CO2, H2O, and energy.
      1. While ammonia forms urea which is excreted into the urine.
      2. Urea is water-soluble and is a waste product and excreted in the urine.
      3. Urea concentration in the glomerular filtrate is the same as in the plasma.
      4. Under normal conditions, 40% of the urea filtered is reabsorbed in the tubules.

Urea formation and excretion

7. Blood urea nitrogen is the main waste product of protein metabolism.
8. Urea forms in the liver with CO2 and is the final product of protein metabolism.

Urea formation

Urea formation

Urea formation and the role of liver

9. Urea is freely filtered and then partially absorbed by the nephron.
10. The BUN is used as the index of glomerular function in the production and its excretion of urea.
    1. Urea reabsorption is increased in hypovolemia so BUN will underestimate Glomerular filtration rate (GFR) and more in hypovolemia.
    2. BUN measures the nitrogen part of the urea.
11. This BUN or urea excreted through the kidney in the urine.
12. The measurement of urea nitrogen gives an idea of the ratio between excretion and production of urea.
13. In the liver amino acids are catabolized and free ammonia is produced.
    1. Ammonia molecules combine to form urea.
    2. The urea through blood goes to the kidney and excreted in the urine.
    3. So BUN depends upon the metabolic function of the liver and excretory function of the kidneys.

Urea excretion cycle

14. The BUN is directly related to the metabolic function of the liver and excretory function of kidneys.
15. In chronic renal diseases, the BUN level correlates better than creatinine with the sign and symptoms of the patient.
    1. As the synthesis of BUN depends upon the liver so patients with severe primary liver disease will have decreased BUN.
    2. In combined liver and renal disease as in hepatorenal syndrome, the BUN may be normal because of poor liver function resulting in decreased formation of urea.
    3. Overall the BUN is less accurate than creatinine for renal diseases.
16. A high protein diet may increase the BUN and low protein intake may decrease its level.
17. Blood urea nitrogen and creatinine ratio also give the idea about the renal, pre-renal, or post-renal diseases.

Clinical condition	BUN
Primary liver disease	decreased
Combined liver and kidney disease (Hepatorenal syndrome)	normal
Dehydration	increased
Overhydration	decreased

Kidneys Dysfunction May Show:

1. The patient may have edema around the eyes, legs, abdomen, and wrist.
2. There is a history of fatigue, poor appetite, lack of concentration, and disturbed sleep.
3. There may be a flank pain, in the kidneys area.
4. There may be burning urination, abnormal discharge, and increased frequency.
5. There is a decrease in the amount of urine.
6. The urine is bloody or coffee-colored and foamy.
7. There may be hypertension.

NORMAL

Source 2

• Urea = 20 to 40 mg/dl
• BUN
  • Blood urea nitrogen (BUN) = 10 to 20 mg /dl
  • Children (BUN) = 5 to 18 mg/dl
  • Infants = 5 to 18 mg/dL
  • Newborn = 3 to 12 mg/dL
  • Cord blood = 21 to 40 mg/dL
• Elderly people may have a higher level than the adult.

Source 1

Age	Urea nitrogen mg/dL
Cor blood	21 to 40
Premature one week	3 to 25
<1 year	4 to 19
Infant/child	5 to 18
18 to 60 year	6 to 20
60 to 90	8 to 23
>90 years	10 to 31

Source 3

• Adult = 10 to 20 mg/dL
• Elderly people have a higher value
• Cord blood = 21 to 40 mg/dL
  • Newborn = 3 to 12 mg/dL
  • Infants = 5 to 18 mg/dL
  • Child = 5 to 18 mg/dL

The level above 100 mg/dl is the critical value indicating severe renal dysfunction.

Increased Urea (BUN) Azotemia Seen In:

A. Impaired Renal Function:

Prerenal Causes:

1. congestive heart failure and Myocardial infarction (CHF).
2. Salt and water depletion
3. Shock
4. Stress
5. Acute MI
6. Hemorrhage into GI tract
7. Dehydration.
8. excessive protein catabolism.
9. Burn.

B. Chronic Renal Diseases:

Renal Causes

1. Glomerulonephritis (GN).
2. Pyelonephritis (PN).
3. Acute tubular necrosis.
4. Renal failure.
5. Diabetes mellitus with ketoacidosis.
6. Anabolic steroids use.
7. Nephrotoxic drugs.

C. Urinary Tract Obstruction:

Postrenal Causes

1. Ureteral obstruction from stones, tumors, or congenital abnormality.
2. Bladder outlet obstruction from prostatic hypertrophy, cancer.
3. Bladder / urethral congenital abnormality.

Causes of azotemia

Decreased Urea (BUN) Seen In:

1. Liver failure.
2. Malnutrition, and low protein diet.
3. Impaired absorption of Celiac disease.
4. Syndrome of inappropriate antidiuretic hormone secretion.
5. Pregnancy.
6. Overhydration.
7. Nephrotic syndrome.

Effect Of Drugs And Other Condition On A BUN:

1. Some of the drugs may cause a decrease in BUN like Dextrose infusion, Phenothiazine, and Thymol.
2. Increased BUN levels may be seen in late pregnancy and infancy because of increased use of proteins.

BUN/Creatinine Ratio:

1. The normal BUN/creatinine ratio is around 10:1.
2. BUN/creatinine ratio in the normal range, in the case of raised BUN and creatinine.  This will suggest intrarenal disease:
   1. Glomerulonephritis.
   2. Tubulointerstitial nephritis.
3. When the BUN / Creatinine ratio is raised will suggest:
   1. Prerenal azotemia.
   2. Postrenal azotemia.
      1. These conditions may be seen in hypovolemia or hypotension.
4. BUN/creatinine ratio decreased is very rare and this may be seen in:
   1. Protein deficiency in the diet.
   2. In severe liver disease.

Interpretation of BUN: Creatinine ratio