Creatinine in the blood is produced by the spontaneous breakdown of creatine and creatine phosphate. Its production and release into body fluids happen at a consistent rate and are proportional to muscle mass. As a result, creatinine concentration varies according to age and gender. The clearance of creatinine from plasma by the kidney is used to calculate GFR. Because RBCs contain significant non-creatinine chromogens, which can generate falsely elevated creatinine assay results, serum or plasma specimens are preferred over whole blood.
Specimens Used For Measuring Creatinine
Creatinine can be measured in serum, heparinized plasma, or diluted urine. Ammonium heparinized plasma should not be used in creatinine quantification procedures that detect ammonia production. Urine is often diluted at a ratio of 1:100 or 1:200.
Creatinine can be stored in serum or plasma for up to a week if the specimen is kept cold. It is critical to separate the cells as soon as possible to avoid hemolysis and reduce ammonia production. Hemolysis results in erroneously increased creatinine levels.
Methods for Quantitative Determination
The Jaffe reaction, the oldest clinical chemistry method still in use, is used in the majority of creatinine methods. Creatinine reacts with alkaline picrate to produce an orange-red solution that can be measured using a spectrophotometer. An acidification step is added to improve the specificity of the reaction and to reduce interference from the various non-creatinine compounds in blood that can also react with the alkaline picrate solution and produce falsely elevated values. Protein, glucose, ascorbic acid, and pyruvate are examples of non-creatinine Jaffe-reacting chromogens. The color of real creatinine is less acid-resistant than the color of non-creatinine compounds. The difference between the two colors is measured photometrically.
In automated analyzers, kinetic alkaline picrate methods and enzymatic creatinine methods are frequently used. Some of the interferences caused by noncreatinine chromogens have been reduced using kinetic methods. A kinetic Jaffe method measures the rate of color change while minimizing interference from slower-reacting chromogens.
Another method for analyzing creatinine is to measure the color produced when creatinine reacts with 3,5-dinitrobenzoate. This method has been successfully adapted to a reagent strip, but the color is less stable than that of the classic Jaffe chromogen assay.
Enzymatic methods, such as creatinine aminohydrolase (creatinine deaminase) or creatininase (creatinine amidohydrolase), make the reaction more specific and more sensitive for creatinine than the colorimetric methods. Although this method has been successfully adapted to a reagent strip, the color is less stable than the classic Jaffe chromogen assay. Creatinine aminohydrolase (creatinine deaminase) or creatininase (creatinine amidohydrolase) enzymes make the reaction more specific and sensitive for creatinine than colorimetric methods.
Creatinine Reference Values
Values in parentheses are in SI units and Creatinine excretion decreases with age.
| Adult men | 0.7-1.3mg/dL (62-115μmol/L) |
| Adult women | 0.6-1.1mg/dL (53-97μmol/L) |
| Adult men | 14-26mg/kg/24h (124-230μmol/kg/24h |
| Adult women | 11-20mg/kg/24h (97-177μmol/kg/24h |
| Male (<40yr) | 90-139mL/min/1.73m2 |
| 1.1 Female (<40yr) | 80-125mL/min/1.73m2 |
Clinical Significance
Creatinine in the blood comes from creatine produced in the body’s muscles. The glomeruli of the kidney filter creatinine freely, with a small percentage secreted by the renal tubules, but it is not reabsorbed in normal circumstances. Creatinine excretion in the urine is relatively constant, and it follows the production of creatinine. Creatinine excretion is impaired in renal disease, as evidenced by elevated blood creatinine levels.
The (Serum Creatinine) SCR concentration is relatively constant in males and slightly higher in females.
Creatinine is a good measure of renal function, especially glomerular filtration, because of its consistency of concentration and excretion. Creatinine concentrations are unaffected by dietary intake, body dehydration, or protein metabolism, making the assay a more reliable single screening index of renal function than the urea assay.
A useful index relates creatinine excretion to muscle mass or lean body weight, taking into account individual body size variables. This is known as the creatinine clearance index (CCR)
Creatinine Clearance: The creatinine clearance rate (CCR) is defined as the number of milliliters of plasma cleared of creatinine by the kidneys per minute. Using the patient’s height and weight, the result is normalized to a standard person’s surface area. CCR is an indirect method for assessing the kidneys’ glomerular filtration functioning capabilities.
To perform this CCR test, timed blood and urine specimens must be collected. For the next 24 hours, all urination must be carefully collected. As new urine specimens are added to the total collection, they are kept cool by being refrigerated. Around 12 hours into the urine collection period, blood is collected. Creatinine levels are measured in the blood (serum or plasma) as well as in timed urine specimens (24 hour). The CCR is determined as follows:
Where U denotes the urine creatinine concentration (mg/dL)
- P the plasma creatinine concentration (mg/dL)
- V the volume of urine excreted per minute in milliliters,
- A patient’s body surface area in square meters, and 1.73 the standard body surface area in square meters.
To determine the patient’s body surface area, a nomogram is used. If the specific patient height and weight data are entered into the system, most automated analyzers can calculate this value.
