Multiple methods for analysis of<unk>  and creatinine have evolved over the years. Most of those in current use are automated and give clinically reliable and reproducible results. There are two general methods for the measurement of urea nitrogen. The diacetyl, or Fearon, reaction develops a yellow chromogen with urea, and this is quantified by photometry. It has been modified for use in autoanalyzers and generally gives relatively accurate results. It still has limited specificity, however, as illustrated by spurious elevations with sulfonylurea compounds, and by colorimetric interference from hemoglobin when whole blood is used. In the more specific enzymatic methods, the enzyme urease converts urea to ammonia and carbonic acid. These products, which are proportional to the concentration of urea in the sample, are assayed in a variety of systems, some of which are automated. One system checks the decrease in absorbance at 340 mm when the ammonia reacts with alpha-ketoglutaric acid. The Astra system measures the rate of increase in conductivity of the solution in which urea is hydrolyzed. Even though the test is now performed mostly on serum, the term<unk>  is still retained by convention. The specimen should not be collected in tubes containing sodium fluoride because the fluoride inhibits urease. Also chloral hydrate and guanethidine have been observed to increase<unk>  values. The 1886 Jaffé reaction, in which creatinine is treated with an alkaline picrate solution to yield a red complex, is still the basis of most commonly used methods for measuring creatinine. This reaction is nonspecific and subject to interference from many noncreatinine chromogens, including acetone, acetoacetate, pyruvate, ascorbic acid, glucose, cephalosporins, barbiturates, and protein. It is also sensitive to pH and temperature changes. One or another of the many modifications designed to nullify these sources of error is used in most clinical laboratories today. For example, the recent kinetic-rate modification, which isolates the brief time interval during which only true creatinine contributes to total color formation, is the basis of the Astra modular system. More specific, non-Jaffé assays have also been developed. One of these, an automated dry-slide enzymatic method, measures ammonia generated when creatinine is hydrolyzed by creatinine iminohydrolase. Its simplicity, precision, and speed highly recommend it for routine use in the clinical laboratory. Only 5-fluorocytosine interferes significantly with the test. Creatinine must be determined in plasma or serum and not whole blood because erythrocytes contain considerable amounts of noncreatinine chromogens. To minimize the conversion of creatine to creatinine, specimens must be as fresh as possible and maintained at pH 7 during storage. The amount of urea produced varies with substrate delivery to the liver and the adequacy of liver function. It is increased by a high-protein diet, by gastrointestinal bleeding (based on plasma protein level of 7.5 g/dl and a hemoglobin of 15 g/dl, 500 ml of whole blood is equivalent to 100 g protein), by catabolic processes such as fever or infection, and by antianabolic drugs such as tetracyclines (except doxycycline) or glucocorticoids. It is decreased by low-protein diet, malnutrition or starvation, and by impaired metabolic activity in the liver due to parenchymal liver disease or, rarely, to congenital deficiency of urea cycle enzymes. The normal subject on a 70 g protein diet produces about 12 g of urea each day. This newly synthesized urea distributes throughout total body water. Some of it is recycled through the enterohepatic circulation. Usually, a small amount (less than 0.5 g/day) is lost through the gastrointestinal tract, lungs, and skin; during exercise, a substantial fraction may be excreted in sweat. The bulk of the urea, about 10 g each day, is excreted by the kidney in a process that begins with glomerular filtration. At high urine flow rates (greater than 2 ml/min), 40% of the filtered load is reabsorbed, and at flow rates lower than 2 ml/min, reabsorption may increase to 60%. Low flow, as in urinary tract obstruction, allows more time for reabsorption and is often associated with increases in antidiuretic hormone (ADH), which increases the permeability of the terminal collecting tubule to urea. During ADH-induced antidiuresis, urea secretion contributes to the intratubular concentration of urea. The subsequent buildup of urea in the inner medulla is critical to the process of urinary concentration. Reabsorption is also increased by volume contraction, reduced renal plasma flow as in congestive heart failure, and decreased glomerular filtration. Creatinine formation begins with the transamidination from arginine to glycine to form glycocyamine or guanidoacetic acid (GAA). This reaction occurs primarily in the kidneys, but also in the mucosa of the small intestine and the pancreas. The GAA is transported to the liver where it is methylated by S-adenosyl methionine (SAM) to form creatine. Creatine enters the circulation, and 90% of it is taken up and stored by muscle tissue.
BUN-to-creatinine ratio
Microalbuminuria
Urine osmolality
Urine urea nitrogen
Renal clearance ratio
Urine protein/creatinine ratio
Urea reduction ratio
Blood urea nitrogen