- Last Update On : 2017-01-07
Urea is the major end product of protein and amino acid catabolism in the liver. Proteins are first degraded to amino acids, which are then deaminated with the production of ammonia (NH3). Ammonia, which is toxic, is then converted to urea, which is nontoxic, in a series of five linked enzymatic reactions that comprise the urea cycle.
Urea is easily diffusible and exists in all body fluids in practically the same concentration. Most of the urea produced in the liver is transported in blood to the kidneys where it is eliminated in urine. Urea is filtered freely by the glomeruli and reabsorbed by the proximal and distal tubules. Plasma urea concentration reflects the balance between urea production in the liver and urea elimination by the kidneys.
Urea concentration is primarily regulated by renal tubular reabsorption, which is highly dependent on urine flow rate. Increased tubular flow, due to blood volume expansion, decreases absorption and BUN concentration. Decreased tubular flow, due to volume depletion or congestive heart failure, increases absorption and urea concentration. Urea concentration is also affected by protein intake (malnutrition or hyperalimentation), endogenous protein metabolism, and liver disease. By itself, urea is a rather poor measure of renal function. Glomerular filtration rate (GFR) must be reduced by around 50% before plasma urea increases above the upper limit of the reference range.
In the United States, plasma or serum urea concentration is expressed as the amount of urea nitrogen. Although urea nitrogen is measured in plasma or serum, the test is called blood urea nitrogen (BUN). The unit of measurement is mg/dL.
Urea consists of two amino (NH2) groups and a carbamyl (C-O) group. Since BUN accounts for only the nitrogen content of urea (molecular weight 28) and urea accounts for the whole molecule (molecular weight 60), urea is approximately two times higher (60/28 = 2.14) than BUN. Urea is expressed in mmol per L.
Most clinicians agree that creatinine is a more specific indicator of glomerular function than BUN. However, the BUN to creatinine ratio may be used as an indirect estimate of renal function. The ratio of BUN to creatinine can be used to determine the etiology of acute renal failure. Normally, the ratio is 10 to 1. The ratio usually exceeds 20 in prerenal failure due to decreased renal perfusion, such as occurs with hypertension, hemorrhage, or dehydration. It is normal in intrinsic renal disease because BUN and creatinine rise proportionately. Postrenal diseases, such as urinary tract obstruction, also increase the ratio above 10.
Kidneys increase the reabsorption of urea to conserve water. Low circulatory states such as heart failure, dehydration and hypovolemic shock may be associated with a mild increase in plasma urea, despite a normal GFR.
The clinical usefulness of the BUN to creatinine ratio is limited by nonrenal factors that increase BUN such as GI bleed, parenteral nutrition, and glucocorticoid therapy. A GI bleed increases BUN more than creatinine because of the increased amino acid absorption from digested blood and hypovolemia. Tissue damage associated with trauma, major surgery, starvation and severe infection can also increase BUN. In general, non-renal causes usually increase BUN mildly, usually to less than 28 mg/dL. In comparison, patients with end-stage renal failure, requiring renal replacement therapy, may have plasma BUN levels greater than 140 mg/dL.
Several diseases may cause a decreased BUN to creatinine ratio of less than 8 to 1. Rhabdomyolysis results in increased production of creatinine. Liver disease, low protein diets and malnutrition decrease the production of urea. Overhydration results in increased urea excretion. Hemodialysis and peritoneal dialysis remove urea more efficiently than creatinine. Some medications may elevate serum creatinine by blocking tubular secretion. The most common examples are cimetidine, trimethoprim, and pyrimethamine. BUN is decreased during pregnancy due to the combined effect of reduced urea production and increased urea excretion, which accompanies increased glomerular filtration rate (GFR).
BUN concentration can be used in patients with chronic renal failure to determine the timing of dialysis. BUN correlates with uremic symptoms better than serum creatinine concentration. BUN levels fall more rapidly than creatinine following dialysis and can be used to assess the adequacy of dialysis.
In summary, increased BUN may be associated with renal failure, urinary tract obstruction, dehydration and gastrointestinal hemorrhage. Decreased BUN may be associated with hepatic failure and decreased protein intake.
Reference range is 8-26 mg/dL for plasma and 12–20 g/24 hour for urine.
Specimen requirement is one SST tube of blood. Hemolysis should be avoided.