Creatinine

Creatinine (from the Greek κρέας, flesh, pronounced, krē-'a-tə-nēn, -ən cre·at·i·nine)  is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body (depending on muscle mass).

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. 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 and trimethoprim 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.)

A more complete estimation of renal function can be made when interpreting the blood (plasma) concentration of creatinine along with that of urea. BUN-to-creatinine ratio (the ratio of blood urea nitrogen 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 nephrons. 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 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 an 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. High creatinine levels indicate a pure test, whereas low amounts of creatinine in the urine either indicate a manipulated test, either through the addition of water in the sample or by drinking excessive amounts of water, or low creatinine may simply be due to factors such as diet, medication, or other factors besides those of conscious urine manipulation.

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, creatinine is typically reported in mg/dL, whereas, in Canada and a few European countries, μmol/litre 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) 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.