Creatinine

Creatinine (from the Greek κρέας, flesh) 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). Chemically, creatinine is a spontaneously formed cyclic derivative of creatine. Creatinine is chiefly filtered out of the blood by the kidneys, though a small amount is actively secreted by the kidneys into the urine. There is little-to-no tubular reabsorption of creatinine. If the filtering of the kidney is deficient, 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 tend to have higher levels of creatinine because they generally have more skeletal muscle mass than women. Vegetarians have been shown to have lower creatinine levels.

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

A rise in blood creatinine levels 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 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 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 (UCr)
Creatinine concentration is also checked during standard urine drug tests. High creatinine levels indicate a pure test while low amounts of creatinine in the urine indicate a manipulated test, either through the addition of water in the sample or by drinking excessive amounts of water.

Interpretation
In the United States, creatinine is typically reported in mg/dL, while 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 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.



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 blockers (ARBs) are taken (ED). 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.