Creatinine is essentially a metabolite of creatine phosphate, a compound that acts as a source of energy in muscle. This molecule is produced at a fairly constant rate in the body, although this does vary depending on muscle mass. Men tend to have higher creatinine levels than women, due to their greater skeletal mass.
The main route of creatinine excretion is through the kidneys, where creatinine is filtered by the glomerulus and also secreted by the proximal tubule. Creatinine is a useful indicator of renal health because it is excreted in the urine as an unchanged and easily measured by-product of muscle metabolism. In a healthy kidney, little or no creatinine is reabsorbed, whereas in kidney disease, the creatinine concentration in the blood may increase. The creatinine concentration in the urine and blood can therefore be used to calculate the rate at which the kidney is clearing creatinine – the creatinine clearance (CrCl) rate. This CrCl rate is correlated with the glomerular filtration rate (GFR), which is important in the clinical assessment of renal function.
An estimated GFR (eGFR) can also be calculated using just the blood level of creatinine. GFR is a useful indicator of kidney function, although calculations using the CrCl rate will give an overestimation of the GFR in cases of severe renal dysfunction, because the proximal tubule secretes excess amounts of creatinine, thereby increasing the overall amount of total creatinine cleared. Drugs that can be used to minimise this excess secretion include cimetidine and trimethoprim and these can therefore be used to improve the accuracy of eGFR.
An alternative to using CrCl calculations and eGFR to indicate renal function is to interpret the plasma concentration of creatinine along with the blood urea level. A test called the BUN (blood urea nitrogen)-to-creatinine ratio is therefore also used as a measure of kidney health, with BUN rising the more kidney function decreases.