Urea estimation: Principle, Methodology and clinical significance

This is also a non protein nitrogenous compound. This accounts for major NPN (75% of NPN). More than 90% of urea is excreted through kidneys, with remaining loses through GI and skin. Kidney disease is associated with urea retention in blood. Urea clearance underestimates GFR as it is reabsorbed. Measurement of urea can indicate kidney functional status and in special circumstances measurement of urea in dialysis fluids is widely used in assessing the adequacy of renal replacement therapy.

Urea reduction = (Predialysis urea – postdialysis urea)/predialysis urea x 100% and if >60% then dialysis is adequate.

Clinical significance:

Extrarenal cause of urea elevation that limit the use of urea to asses kidney function are,
high protein intake, high protein catabolism (exercise, fever), dehydration, etc. During this condition creatinine is normal. In postrenal (obstructive) conditions like malignancy, nephrolithiasis, prostatism, both plasma are creatinine are elevated although urea elevation is higher because of increased back diffusion of urea. The measurement of urea nitrogen/creatinine ratio can be used as crude discrimination between prerenal and postrenal azotemia. For normal individual the reference interval for the ratio is between 12 and 20 mg urea/mg creatinine. Increase plasma urea with normal creatinine gives rise to high ratio and seen in prerenal states. Low ratio is associated with elevated creatinine concentrations and denotes either postrenal obstruction or prerenal azotemia superimposed on kidney disease.

Urea clearance is poor indicator of GFR as its production rate is not constant and depends on diet, hydration, urea cycle enzymes, health status, etc. Also there is back diffusion from kidney. Sometimes BUN is measured so, 60g urea contains 28g nitrogen, so factor 0.467 for converting urea mass units to urea nitrogen, and 2.14 for converting urea nitrogen mass units to those of urea.

Methodology:

Chemical methods:

Chemical methods for urea are based on the Fearon reaction where diazine is formed that absorb at 540 nm

Enzymatic method:

It uses both enzymatic kinetic method where decrease in absorbance at 340 nm monitored. 

End point method utilizing Berthelot reaction – color of indophenol is 

The enzymatic method of glutamate dehydrogenase is a reference method.

Other POCT using dry reagents are available using potentiometric and conductometric measurement using ammonium ion selective electrode and conductance measurement of urea ion respectively. 

Reference interval:

Adult = 10-50 mg/dl

IN ESRD this level may go to >100 mg/dl.