In a series of five enzymatically controlled reactions, known collectively as the “urea cycle”, toxic ammonia resulting from protein breakdown is converted to non-toxic urea. Proteins are first degraded to constituent amino acids, which are in turn degraded (deaminated), with production of ammonia (NH3), which is toxic. It is the principal nitrogenous end product of protein and amino acid catabolism. Urea is a small organic molecule (MW 60) comprising two amino (NH2) groups and a linked carbamyl (C-O) group: Background physiology - urea production and excretion In recent times, plasma creatinine estimation has emerged as the preferred first-line test for laboratory assessment of renal function, but measurement of plasma/serum urea concentration continues to have clinical value in the 21st century – albeit much less so than was once the case. Improved methods of blood urea estimation in the early decades of the 20th century allowed plasma/serum urea concentration to emerge as the most widely used routine test of renal function, a pre-eminence that continued for close to 60 years. In the meantime, it was clear by the mid-19th century that kidney disease was associated with reduced urinary excretion of urea, and estimation of urea in urine for clinical purposes was established by this time. The presence of urea in blood and confirmation of its identity with that found in urine was demonstrated in 1822 but reliable methodology for determination of the concentration of urea in blood had to wait until the early years of the 20th century. This synthesis, which was serendipitously achieved by Friedrich Wöhler in 1828, has particular significance because it marked the birth of organic chemistry and raised the first doubts about the then long-held popular belief that an undefined “vital force” was required to synthesize chemicals involved in the process of living organisms. Urea was the first organic chemical to be synthesized from inorganic chemicals. The first pure preparation of urea from urine was made in 1817 by the English physician/ chemist William Prout. Discovery of urea is credited to the Dutch physician Hermann Boerhaave who first isolated it, in impure form, from urine around 1727. The application of chemistry to medicine, from which emerged the discipline of chemical pathology (clinical chemistry) in the mid-19th century, has its origins in the early 18th century, when urine, the most readily available of body fluids, was first subjected to chemical analysis.Īs the most abundant nonaqueous constituent of urine, urea featured from the beginning of this long story. ![]() Urea owns special historical significance compared with most other analytes currently measured in the clinical laboratory or at the point of care. The second article will deal with the value of urea measurement as an adjunct to creatinine measurement the focus here will be the urea:creatinine ratio.īy way of introduction, this first article begins with a brief historical perspective. The main focus of this first article will be physiological topics, such as urea production and renal processing of urea, along with the causes of increased and reduced plasma/serum urea concentration.Ĭonsideration will also be given to the limitations of urea measurement for assessment of renal function. This is the first of two articles that together aim to explore current understanding of the clinical value of measuring serum or plasma urea concentration. ![]() It is eliminated from the body almost exclusively by the kidneys in urine, and measurement of its concentration, first in urine and later in blood, has had clinical application in the assessment of kidney (renal) function for well over 150 years. Urea is the principal nitrogenous waste product of metabolism and is generated from protein breakdown.
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