CREATININE

Creatinine is a naturally occurring nitrogen-containing compound formed from the breakdown of creatine in muscle metabolism.
Creatinine is widely used as a biochemical reference standard in clinical analysis and kidney function studies.
Creatinine is also valuable in pharmaceutical research, diagnostic testing, and analytical method development.

CAS Number: 60-27-5
EC Number: 200-466-7
Molecular Formula: C4H7N3O
Molecular Weight: 113.12 g/mol

Synonyms: 2-Imino-1-methylimidazolidin-4-one, 1-Methylglycocyamidine, 1-Methylhydantoin-2-imide, Kreatinin, Creatinine,heated, Kreatininum, 2-amino-1-methylimidazolin-4-one, 2-amino-3-methyl-4H-imidazol-5-one, 2-amino-1-methyl-1,5-dihydro-4H-imidazol-4-one, 4H-Imidazol-4-one, 2-amino-1,5-dihydro-1-methyl-, creatinina, NSC-13123, AYI8EX34EU, 2-Amino-1,5-dihydro-1-methyl-4H-imidazol-4-one, CHEMBL65567, CHEBI:16737, NSC-760435, CREATININE (II), CREATININE [II], IMIDAZOLIDIN-4-ONE, 2-IMINO-1-METHYL, CREATININE (USP-RS), CREATININE [USP-RS], RefChem:5708, 200-466-7, 60-27-5, Creatine anhydride, creatinine, DTXSID8045987, 2-Imino-N-methylhydantoin, 2-Amino-1-methyl-2-imidazolin-4-one, 2-Amino-1-methyl-1,5-dihydroimidazol-4-one, Creatinine (VAN) (8CI), 4H-Imidazol-4-one, 2-imino-1,5-dihydro-1-methyl-, Spectrum_000429, CREATININE [MI], Spectrum2_000764, Spectrum3_001717, Spectrum4_001806, Spectrum5_000511, bmse000155, bmse000789, bmse001001, CREATININE [MART.], CREATININE [WHO-DD], BSPBio_003334, KBioGR_002415, KBioSS_000909, MLS001306430, DivK1c_000351, SPECTRUM1600300, SPBio_000808, orb1310556, orb3141432, Creatinine, anhydrous, >=98%, HMS501B13, KBio1_000351, KBio2_000909, KBio2_003477, KBio2_006045, KBio3_002554, NINDS_000351, Creatinine, 98.5-102.0%, HMS2233P20, HMS3372L11, Pharmakon1600-01600300, CCG-40153, MSK001352, NSC760435, STK530885, 2-Imino-1-methyl-imidazolidin-4-one, AKOS000121140, AKOS005458367, 2-Imino-1-methyl-4-imidazolidinone #, Creatinine, NIST(R) SRM(R) 914a, SDCCGMLS-0066864.P001, IDI1_000351, NCGC00095762-02, NCGC00247664-01, 4H-Imidazol-4-one,5-dihydro-1-methyl-, AS-12671, SMR000718791, MSK001352-100000-5ml, 2-amino-1-methyl-1,5-dihydro-imidazol-4-one, C00791, D03600, AB00052404_03, AB00052404_04, 2-amino-3-methyl-4H-imidazol-5-one,dichlorozinc, 2-amino-4,5-dihydro-1-methyl-1H-imidazol-4-one, 2-Imino-1,5-dihydro-1-methyl-4H-imidazol-4-one, AO-840/40806907, SR-01000837526, SR-01000837526-3, BRD-K13495773-001-11-4, BRD-K13495773-001-12-2, F0001-1578, C5CF605C-9352-48F2-A5A4-561B97D42C30, Creatinine, United States Pharmacopeia (USP) Reference Standard, Creatinine, Pharmaceutical Secondary Standard; Certified Reference Material, InChI=1/C4H7N3O/c1-7-2-3(8)6-4(7)5/h2H2,1H3,(H2,5,6,8)

Creatinine is a waste product that comes from the digestion of protein in your food and the normal breakdown of muscle tissue.
Creatinine is removed from the blood through your kidneys.

Everyone has some creatinine in their blood, but too much can be a sign of a possible kidney problem.
Creatinine is a waste product created by your muscles.

The more muscle you have, the more creatinine your body produces.
This waste product is normally filtered out of your blood by your kidneys and eliminated through urine.

Creatinine is a nitrogen-containing organic compound formed mainly from the spontaneous breakdown of creatine and creatine phosphate.
Creatinine is widely used as a biochemical reference compound in clinical, pharmaceutical, and laboratory research, particularly for evaluating kidney filtration through blood and urine measurements.
Creatinine is also used as an analytical standard in biochemical assays and method development.

Creatinine is a breakdown product of creatine phosphate from muscle and protein metabolism.
Creatinine is released at a constant rate by the body (depending on muscle mass).

Creatinine is a lactam obtained by formal cyclocondensation of creatine.
Creatinine is a metabolite of creatine.

Creatinine has a role as a diagnostic agent and a human metabolite.
Creatinine is a lactam and an imidazolidinone.

Creatinine is functionally related to a creatine.
Creatinine has been used in trials studying the treatment of Amyotrophic Lateral Sclerosis.
creatinine tautomer has been reported in Punica granatum, Morus alba, and other organisms with data available.

Interpretation of Creatinine:
In the United States and in most European countries creatinine is usually reported in mg/dL, whereas in Canada, Australia and a few European countries, such as the UK, μmol/L is the usual unit.
One mg/dL of creatinine equals 88.4 μmol/L.

The typical human reference ranges for serum creatinine are 0.5 mg/dL to 1.0 mg/dL (about 45 μmol/L to 90 μmol/L) for women and 0.7 mg/dL to 1.2 mg/dL (60 μmol/L to 110 μmol/L) for men.
The significance of a single creatinine value must be interpreted in light of the patient's muscle mass.
Patients with greater muscle mass have higher creatinine concentrations.

The trend of serum creatinine concentrations over time is more important than the absolute creatinine concentration.

Serum creatinine concentrations may increase when an ACE inhibitor (ACEI) is taken for heart failure and chronic kidney disease.
ACE inhibitors provide survival benefits for patients with heart failure and slow disease progression in patients with chronic kidney disease.

An increase not exceeding 30% is to be expected with use of an ACE inhibitor.
Therefore, an ACE inhibitor should not be withdrawn when the serum creatinine increases, unless the increase exceeds 30% or hyperkalemia develops.

Biological Relevance of Creatinine:
Creatinine is formed by the spontaneous, non-enzymatic breakdown of creatine and phosphocreatine.
Creatinine is synthesised from glycine and arginine (via guanidinoacetate) and is reversibly phosphorylated by creatine kinase to phosphocreatine.

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

Creatinine is synthesized primarily in the liver by methylation of glycocyamine (guanidino acetate, synthesized in the kidney from the amino acids arginine and glycine) by S-adenosyl methionine.
Creatinine is then transported in the blood to other organs, muscles, and the brain, where it is phosphorylated to phosphocreatine, a high-energy compound.
Creatinine conversion to phosphocreatine is catalysed by creatine kinase; spontaneous formation of creatinine occurs during the reaction.

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 filtration in the kidney is deficient, blood creatinine concentrations rise.
Therefore, creatinine concentrations in blood and urine may be used to calculate the creatinine clearance (CrCl), which correlates approx. with the glomerular filtration rate (GFR).
Blood creatinine concentrations may also be used alone to estimate the GFR (eGFR).

The GFR is clinically important as a measurement of kidney function.
However, in cases of severe kidney dysfunction the CrCl rate will overestimate the GFR, because hypersecretion of creatinine by the proximal renal tubules 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, in particular in severe kidney dysfunction. (In the absence of secretion, creatinine behaves like inulin.)

An alternative estimation of kidney 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 concentration raised out of proportion to the creatinine may indicate a prerenal problem, such as volume depletion.

Counterintuitively, supporting the observation of higher creatinine production in women than in men, and putting into question the algorithms for GFR that do not distinguish for sex, women have higher muscle protein synthesis and higher muscle protein turnover across their life span.
As HDL supports muscle anabolism, higher muscle protein turnover links increased Creatinine to the generally higher serum HDL in women compared with serum HDL in men.

Antibacterial and potential immunosuppressive properties:
Studies suggest that creatinine can be effective in killing bacteria of many species, both Gram positive and Gram negative, as well as diverse antibiotic-resistant bacterial strains.
Creatinine appears not to affect the growth of fungi and yeasts; this can be used to isolate slower growing fungi free from the normal bacterial populations found in most environmental samples.

The mechanism by which creatinine kills bacteria is not currently known.
Some reports also suggest that creatinine may have immunosuppressive properties.

Uses of Creatinine:
Creatinine is used as a bulking agent for freeze drying.
Final metabolic product of Creatinine that is found in all bodily fluids.
Creatinine is used in determination of renal function.

Creatinine is widely used as a biochemical marker for evaluating kidney function through blood and urine analysis.
Creatinine serves as an analytical standard in clinical chemistry, diagnostic assays, and laboratory method validation.

Creatinine is also used in pharmaceutical research, biochemical studies, and the development of reference materials.
Creatinine is commonly employed in studies related to creatine metabolism, renal clearance, and physiological monitoring.

Diagnostic use:
Serum creatinine is the most commonly used indicator (although not a direct measure) of renal function.
A raised creatinine is not always representative of a true reduction in GFR.

A high reading may be due to: increased production of creatinine (with no association to reduced kidney function), interference with the assay, or reduced tubular secretion of creatinine.
An increase in serum creatinine can be due to increased ingestion of cooked meat (which contains creatinine converted from creatine by the heat from cooking) or excessive intake of protein and creatine supplements, taken to enhance athletic performance.
Intense exercise can increase creatinine by increasing muscle breakdown.

Hypovolaemia of any cause, may have an associated increase in creatinine concentration, secondary to the expected reduction in GFR.
This is pre-renal impairment of kidney function.

Several medications and chromogens can interfere with the chemical assay.
Creatinine secretion by the renal tubules can be blocked by some medications, again increasing measured creatinine.

Serum creatinine:
Diagnostic serum creatinine studies are used to determine renal function.
The reference interval is 0.6–1.3 mg/dL (53–115 μmol/L).
Creatinine is simple to measure serum creatinine, and it is the most commonly used indicator of renal function.

A rise in blood creatinine concentration is a late marker, observed only with marked damage to functioning nephrons.
The test is therefore unsuitable for detecting early-stage kidney disease.

A better estimate of kidney function is given by calculating the estimated glomerular filtration rate (eGFR).
eGFR can be calculated without a 24-hour urine collection, using serum creatinine concentration and some or all of the following variables: sex, age, and weight, as suggested by the American Diabetes Association.

Many laboratories will automatically calculate eGFR when a creatinine test is requested.
Algorithms to estimate GFR from creatinine concentration and other parameters are discussed in the renal function article.
Unfortunately, the MDRD Study equation was developed in people with chronic kidney disease, and its major limitations are imprecision and systematic underestimation of measured GFR (bias) at higher/normal values.

A concern as of late 2010 relates to the adoption of a new analytical method, and the possible effect 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 comparative overestimation of the corresponding calculated GFR in some patients with normal renal function.

A few medicines are dosed even in normal renal function using that derived value of GFR.
The dose, unless further modified, could then 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 of carboplatin, a chemotherapy drug, to specified maxima.

Urine creatinine:
Males produce approx. 150 μmol to 200 μmol of creatinine per kilogram of body weight per 24 h, while females produce approx. 100 μmol to 150 μmol/kg/24 h.
In normal circumstances, all the creatinine produced is excreted in the urine.

Creatinine concentration is checked during standard urine drug tests.
An expected creatinine concentration indicates that the test sample is undiluted, whereas low amounts of creatinine in the urine indicate either a manipulated test or low initial baseline creatinine concentrations.
Test samples considered manipulated due to low creatinine are not tested, and the test is sometimes considered failed.

Chemistry of Creatinine:
In chemical terms, creatinine is a lactam and an imidazolidinone.

In the laboratory it can be produced from the cyclization of Creatinine using hydrochloric acid:
C4H9N3O2 + HCl → C4H7N3O·HCl + H2O

This produces creatinine hydrochloride.

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 at around 300 °C.

Stability and Reactivity of Creatinine:

Chemical stability:
Stable under normal storage and handling conditions.

Conditions to avoid:
Avoid excessive heat, moisture, and incompatible materials.

Incompatible materials:
Strong oxidizing agents, strong acids, and strong bases.

Hazardous decomposition products:
Thermal decomposition may produce carbon oxides and nitrogen-containing fumes.

Handling and Storage of Creatinine:

Safe handling:
Avoid dust formation and contact with skin and eyes.
Use adequate ventilation.

Storage conditions:
Store tightly closed in a cool, dry, well-ventilated place.

First Aid Measures of Creatinine:

Inhalation:
Move to fresh air if dust is inhaled.

Skin contact:
Wash with soap and water.

Eye contact:
Rinse carefully with water for several minutes.

Ingestion:
Rinse mouth and seek medical advice if discomfort occurs.

Firefighting Measures of Creatinine:

Suitable extinguishing media:
Use water spray, foam, dry chemical, or CO₂.

Protective equipment:
Firefighters should wear suitable protective equipment.

Accidental Release Measures of Creatinine:

Personal precautions:
Avoid dust formation and ensure adequate ventilation.

Cleanup methods:
Sweep or collect carefully into a suitable closed container.

Exposure Controls / Personal Protective Equipment of Creatinine:

Engineering controls:
Provide adequate ventilation.

Personal protection:
Wear protective gloves, safety glasses, and suitable protective clothing.
Use respiratory protection if significant dust is generated.

Identifiers of Creatinine:
CAS Number: 60-27-5
Beilstein Reference: 112061
ChEBI: CHEBI:16737
ChEMBL: ChEMBL65567
ChemSpider: 21640982
DrugBank: DB11846
ECHA InfoCard: 100.000.424
EC Number: 200-466-7
KEGG: D03600
MeSH: Creatinine
PubChem CID: 26009888
588 minor tautomer
UNII: AYI8EX34EU
CompTox Dashboard (EPA): DTXSID8045987
InChI: InChI=1S/C4H7N3O/c1-7-2-3(8)6-4(7)5/h2,8H,1H3,(H2,5,6)
Key: BTXYOFGSUFEOLA-UHFFFAOYSA-N
InChI=1/C4H7N3O/c1-7-2-3(8)6-4(7)5/h2H2,1H3,(H2,5,6,8)
Key: DDRJAANPRJIHGJ-UHFFFAOYAV
SMILES: CN1CC(=O)N=C1N, CN1CC(=O)NC1=N

CAS Number: 60-27-5
EC Number: 200-466-7
Molecular Formula: C4H7N3O
Molecular Weight: 113.12 g/mol
PubChem CID: 588
IUPAC Name: 2-Amino-3-methyl-4H-imidazol-5-one
InChIKey: DDRJAANPRJIHGJ-UHFFFAOYSA-N
SMILES: CN1CC(=O)N=C1N

Properties of Creatinine:
Chemical formula: C4H7N3O
Molar mass: 113.120 g·mol−1
Appearance: White crystals
Density: 1.09 g cm−3
Melting point: 300 °C (572 °F; 573 K) (decomposes)
Solubility in water: 1 part per 12
90 g/L at 20°C

log P: −1.76
Acidity (pKa): 12.309
Basicity (pKb): 1.688
Isoelectric point: 11.19

Molecular Weight: 113.12 g/mol
XLogP3: -1.8
Hydrogen Bond Donor Count: 1
Hydrogen Bond Acceptor Count: 1
Rotatable Bond Count: 0
Exact Mass: 113.058911855 Da
Monoisotopic Mass: 113.058911855 Da
Topological Polar Surface Area: 58.7 Ų
Heavy Atom Count: 8
Complexity: 151
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

Appearance: White crystalline powder
Odor: Odorless
Molecular Formula: C4H7N3O
Molecular Weight: 113.12 g/mol
Melting Point: approx. 300 °C (decomposes)
Solubility: Soluble in water; slightly soluble in alcohol
Density: approx. 1.5 g/cm³
pKa: approx. 4.8

Thermochemistry of Creatinine:
Heat capacity (C): 138.1 J K−1 mol−1 (at 23.4 °C)
Std molar entropy (S⦵298): 167.4 J K−1 mol−1
Std enthalpy of formation (ΔfH⦵298): −240.81–239.05 kJ mol−1
Std enthalpy of combustion (ΔcH⦵298): −2.33539–2.33367 MJ mol−1

Names of Creatinine:

Preferred IUPAC name:
2-Amino-1-methyl-5H-imidazol-4-one

Other name:
2-Amino-1-methylimidazol-4-ol