Creatinine - Biological Relevance

Biological Relevance

Creatine is primarily synthesized in the liver from the methylation of glycocyamine (guanidino acetate, synthesized in the kidney from the amino acids arginine, glycine, and methionine) by S-Adenosyl-L-Methionine. It is then transported through blood to the other organs, muscle, and brain where, through phosphorylation, it becomes the high energy compound phosphocreatine. During the reaction Creatine:phosphocreatine, catalyzed by Creatine Kinase, spontaneous conversion to creatinine may occur.

Creatinine is chiefly filtered out of the blood by the kidneys (glomerular filtration and proximal tubular secretion). There is little or 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 active secretion of creatinine from the proximal tubule 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.

One-percent to two-percent of muscle creatine is converted to creatinine each day. Men tend to have higher levels of creatinine than women because they generally have a greater mass of skeletal muscle. Increased dietary intake of creatine or eating a lot of meat can increase daily creatinine excretion. Vegetarians have been shown to have lower creatinine levels.