Creatinine

Creatinine

Overview
Creatinine is a break-down product of creatine phosphate in muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

, and is usually produced at a fairly constant rate by the body (depending on muscle mass). Creatinine starts to decompose above 295 °C.

In chemical terms, creatinine is a spontaneously formed cyclic derivative of creatine.
Creatinine is chiefly filtered out of the blood by the kidneys (glomerular filtration and proximal tubular secretion).
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Creatinine is a break-down product of creatine phosphate in muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

, and is usually produced at a fairly constant rate by the body (depending on muscle mass). Creatinine starts to decompose above 295 °C.

In chemical terms, creatinine is a spontaneously formed cyclic derivative of creatine.
Creatinine is chiefly filtered out of the blood by the kidneys (glomerular filtration and proximal tubular secretion). There is little-to-no tubular reabsorption of creatinine. If the filtering of the kidney is deficient, creatinine blood levels rise. Therefore, creatinine levels in blood and urine may be used to calculate the creatinine clearance (CrCl), which reflects the glomerular filtration rate (GFR).

The GFR is clinically important because it is a measurement of renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...

. However, in cases of severe renal dysfunction, the creatinine clearance rate will be "overestimated" because the active secretion of creatinine will account for a larger fraction of the total creatinine cleared. Ketoacids, cimetidine
Cimetidine
Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...

 and trimethoprim
Trimethoprim
Trimethoprim is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections.It belongs to the class of chemotherapeutic agents known as dihydrofolate reductase inhibitors...

 reduce creatinine tubular secretion and therefore increase the accuracy of the GFR estimate, particularly in severe renal dysfunction. (In the absence of secretion, creatinine behaves like inulin
Inulin
Inulins are a group of naturally occurring polysaccharides produced by many types of plants. They belong to a class of fibers known as fructans. Inulin is used by some plants as a means of storing energy and is typically found in roots or rhizomes...

.)

A more complete estimation of renal function can be made when interpreting the blood (plasma) concentration of creatinine along with that of urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....

. BUN-to-creatinine ratio
BUN-to-creatinine ratio
In medicine, the BUN-to-creatinine ratio is the ratio of two serum laboratory values, the blood urea nitrogen and serum creatinine . Outside the United States, particularly in Canada and Europe, the truncated term urea is used and the units are different...

 (the ratio of blood urea nitrogen
Blood urea nitrogen
The blood urea nitrogen test is a measure of the amount of nitrogen in the blood in the form of urea, and a measurement of renal function. Urea is a by- product from metabolism of proteins by the liver and is removed from the blood by the kidneys.-Physiology:The liver produces urea in the urea...

 to creatinine) can indicate other problems besides those intrinsic to the kidney; for example, a urea level raised out of proportion to the creatinine may indicate a pre-renal problem such as volume depletion.

Men generally tend to have higher levels of creatinine because they have more skeletal muscle mass than women. Vegetarians have been shown to have lower creatinine levels.

There exists several tautomers of creatinine. Ordered by contribution, they are:
  • 2-Amino-1-methyl-1H-imidazol-4-ol or 2-Amino-1-methylimidazol-4-ol
  • 2-Amino-1-methyl-4,5-dihydro-1H-imidazol-4-one
  • 2-Imino-1-methyl-2,3-dihydro-1H-imidazol-4-ol or 2-Imino-1-methyl-3H-imidazol-4-ol
  • 2-Imino-1-methylimidazolidin-4-one
  • 2-Imino-1-methyl-2,5-dihydro-1H-imidazol-4-ol or 2-Imino-1-methyl-5H-imidazol-4-ol

Serum creatinine


Measuring serum creatinine is a simple test and it is the most commonly used indicator of renal function.

A rise in blood creatinine level is observed only with marked damage to functioning nephron
Nephron
The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....

s. Therefore, this test is not suitable for detecting early-stage kidney disease. A better estimation of kidney function is given by the creatinine clearance (CrCl) test. Creatinine clearance can be accurately calculated using serum creatinine concentration and some or all of the following variables: sex, age, weight, and race, as suggested by the American Diabetes Association
American Diabetes Association
The American Diabetes Association is a United States-based association working to fight the consequences of diabetes, and to help those affected by diabetes...

 without a 24-hour urine collection. Some laboratories will calculate the CrCl if written on the pathology request form, and the necessary age, sex, and weight are included in the patient information.

A current concern in late 2010 relates to the adoption of a new analytical methodology, and a possible impact this may have in clinical medicine. All clinical laboratories in the US will soon use a new standardized Isotope Dilution Mass Spectrometry (IDMS) method to measure serum creatinine. IDMS appears to give lower values compared to older methods when the serum creatinine values are relatively low, for example 0.7 mg/dL. The IDMS method would result in a comparative overestimation of the corresponding calculated Glomerular Filtration Rate (GFR) in some patients with normal renal function. A few medicines are dosed even in normal renal function on that derived GFR. The dose, unless further modified, could now be higher than desired, potentially causing increased drug-related toxicity. To counter the effect of changing to IDMS, new FDA guidelines have suggested limiting doses to specified maximums with carboplatin, a chemotherapy drug.

A recent Japanese study suggests that a lower-serum creatinine level is associated with an increased risk for the development of type 2 diabetes in Japanese men..

Urine creatinine


Creatinine concentration is also checked during standard urine drug tests. Normal creatinine levels indicate that the test sample is undiluted, whereas low amounts of creatinine in the urine either indicate either a manipulated test or low individual baseline creatinine levels. Test samples that are considered manipulated due to low creatinine aren't tested and the test is sometimes considered failed.

It should be noted that diluted samples may not always be due to a conscious effort of subversion and diluted samples cannot be proved to be intentional, but are only assumed to be. Random urine creatinine levels have no standard reference ranges. They are usually used with other tests to reference levels of other substances measured in the urine. Diuretics, such as coffee and tea, cause more frequent urination, thus potently decreasing creatinine levels. A decrease in muscle mass will also cause a lower reading of creatinine, as will pregnancy.

Interpretation


In the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

, creatinine is typically reported in mg/dL, whereas, in Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...

 and a few European countries, μmol
Mole (unit)
The mole is a unit of measurement used in chemistry to express amounts of a chemical substance, defined as an amount of a substance that contains as many elementary entities as there are atoms in 12 grams of pure carbon-12 , the isotope of carbon with atomic weight 12. This corresponds to a value...

/litre
Litre
pic|200px|right|thumb|One litre is equivalent to this cubeEach side is 10 cm1 litre water = 1 kilogram water The litre is a metric system unit of volume equal to 1 cubic decimetre , to 1,000 cubic centimetres , and to 1/1,000 cubic metre...

 may be used. 1 mg/dL of creatinine is 88.4 μmol/L.

The typical human reference ranges for serum creatinine are 0.5 to 1.0 mg/dL (about 45-90 μmol/L) for women and 0.7 to 1.2 mg/dL (60-110 μmol/L) for men. While a baseline (medicine)
Baseline (medicine)
A baseline in medicine is information found at the beginning of a study or other initial known value which is used for comparison with later data. The concept of a baseline is essential to the daily practice of medicine in order to establish a relative rather than absolute meaning to data...

 serum creatinine of 2.0 mg/dL (150 μmol/L) may indicate normal kidney function in a male body builder, a serum creatinine of 1.2 mg/dL (110 μmol/L) can indicate significant renal disease in an elderly female. for male reference range are 60-120 μmol/L and for female it is 50-110 μmol/L (Ref: Australian Medicine Handbook)
More important than absolute creatinine level is the trend of serum creatinine levels over time.

Creatinine levels may increase when ACE inhibitors (ACEI) or angiotensin II receptor antagonists (or angiotensin receptor blockers, ARBs) are taken. Using both ACEI & ARB concomitantly will increase creatinine levels to a greater degree than either of the two drugs would individually. An increase of <30% is to be expected with ACEI or ARB use.