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The Benefits and Dangers of Creatinine

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From Wikipedia, the free encyclopedia
60-27-5 Yes
3DMet B00175
ChEBI CHEBI:16737 
ChemSpider 21640982 Yes
EC Number 200-466-7
Jmol 3D model Interactive image
KEGG D03600 Yes
MeSH Creatinine
PubChem 26009888
588 minor tautomer
UN number 1789
Molar mass 113.12 g·mol−1
Appearance White crystals
Density 1.09 g cm−3
Melting point 300 °C (572 °F; 573 K)[1] (decomposes)
Acidity (pKa)
Basicity (pKb)

Creatinine (/kriˈætnn/ or /kriˈætnin/; Greek: κρέας, translit. flesh) is a breakdown product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body (depending on muscle mass).


Biological relevance

Serum creatinine (a blood measurement) is an important indicator of renal health because it is an easily measured byproduct of muscle metabolism that is excreted unchanged by the kidneys. Creatinine itself is produced[3] via a biological system involving creatine, phosphocreatine (also known as creatine phosphate), and adenosine triphosphate (ATP, the body’s immediate energy supply).

Creatine is synthesized primarily in the liver from the methylation of glycocyamine (guanidino acetate, synthesized in the kidney from the amino acids arginine and glycine) by S-adenosyl methionine. It is then transported through blood to the other organs, muscle, and brain, where, through phosphorylation, it becomes the high-energy compound phosphocreatine.[4] Creatine conversion to phosphocreatine is catalyzed by creatine kinase; spontaneous formation of creatinine occurs during the reaction.[5]

Creatinine is removed from the blood chiefly by the kidneys, primarily by glomerular filtration, but also by proximal tubular secretion. Little or no tubular reabsorption of creatinine occurs. If the filtration in 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 correlates with the glomerular filtration rate (GFR). Blood creatinine levels may also be used alone to calculate the estimated GFR (eGFR).

The GFR is clinically important because it is a measurement of renal function. However, in cases of severe renal dysfunction, the CrCl rate will overestimate the GFR because hypersecretion of creatinine by the proximal tubules will account for a larger fraction of the total creatinine cleared.[6] Ketoacids, cimetidine, and trimethoprim reduce creatinine tubular secretion and, therefore, increase the accuracy of the GFR estimate, in particular in severe renal dysfunction. (In the absence of secretion, creatinine behaves like inulin.)

An alternate 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 prerenal problem such as volume depletion.

Each day, 1-2% of muscle creatine is converted to creatinine.[4] Men tend to have higher levels of creatinine than women because, in general, they have a greater mass of skeletal muscle.[4] Increased dietary intake of creatine or eating a lot of protein (like meat) can increase daily creatinine excretion.[4]

Diagnostic use

Serum creatinine

Measuring serum creatinine is a simple test, and it is the most commonly used indicator of renal function.[4]

A rise in blood creatinine level is a late marker, observed only with marked damage to functioning nephrons. Therefore, this test is unsuitable for detecting early-stage kidney disease. A better estimation of kidney function is given by calculating the estimated glomerular filtration rate (eGFR). eGFR 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.[7] Many laboratories will automatically calculate eGFR when a creatinine test is requested. Extensive discussion of eGFR algorithms can be found in the Renal function article.

A concern as of late 2010 relates to the adoption of a new analytical methodology, and a possible impact this may have in clinical medicine. Most clinical laboratories now align their creatinine measurements against a new standardized isotope dilution mass spectrometry (IDMS) method to measure serum creatinine. IDMS appears to give lower values than 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 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 maxima with carboplatin, a chemotherapy drug.[8]

In a recent Japanese study, a lower serum creatinine level was found to be associated with an increased risk for the development of type 2 diabetes in Japanese men.[9]

Urine creatinine

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


In the United States and in most European countries creatinine is typically reported in mg/dL, whereas in Canada, Australia,[10] and a few European countries, μmol/L may be used. One 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. The significance of a single creatinine value must be interpreted in light of the patient’s muscle mass. A patient with a greater muscle mass will have a higher creatinine level. While a baseline serum creatinine of 2.0 mg/dL (177 μmol/L) may indicate normal kidney function in a male body builder, a serum creatinine of 1.6 mg/dL (110 μmol/L) can indicate significant renal disease in an elderly female.[citation needed]

Reference ranges for blood tests, comparing blood content of creatinine (shown in apple green) with other constituents

The trend of serum creatinine levels over time is more important than absolute creatinine level.

Creatinine levels may increase when an ACE inhibitor (ACEI) or angiotensin II receptor antagonist (or angiotensin receptor blocker, ARB) is taken. Using both ACEI and 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.


In chemical terms, creatinine is a spontaneously formed cyclic derivative of creatine. Several tautomers of creatinine exist; 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)

Creatinine starts to decompose around 300 °C.

See also




  1. Faull R (2007). “Prescribing in renal disease”. Australian Prescriber. 30 (1): 17–20.

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About Patrick Ireland

My name is Patrick Ireland, living in the Philippines with my wife and two daughters. I have been studying the web for over a decade. Now that I am 60 years old, I am starting to apply some of the knowledge that I have gained. "Learn from yesterday, live for today, hope for tomorrow. The important thing is to never stop questioning." -Einstein.

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