Creatinine

reatinine (/kriˈætɪnɪn/ or /kriˈætɪniːn/; from Greek: κρέας, translit. kreas, lit. ‘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).

External linksBiological relevance[edit]

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 approximately 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. 

Antibacterial and potential immunosuppressive properties[edit]

Studies indicate creatinine can be effective at killing bacteria of many species in both the Gram positive and Gram negative as well as diverse antibiotic resistant bacterial strains.[8] Creatinine appears not to affect growth of fungi and yeast; 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 presently known. A recent report also suggests that creatinine may have immunosuppressive properties.[9][10]

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] The conversion is nonenzymatic and irreversible.[7] 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]

Antibacterial and potential immunosuppressive properties[edit]

Studies indicate creatinine can be effective at killing bacteria of many species in both the Gram positive and Gram negative as well as diverse antibiotic resistant bacterial strains.[8] Creatinine appears not to affect growth of fungi and yeast; 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 presently known. A recent report also suggests that creatinine may have immunosuppressive properties.[9][10]

References[edit]

  1. ^ Jump up to:
    a b Merck Index, 11th Edition, 2571
  2. ^ “Creatinine, anhydrous – CAS 60-27-5”. Scbt.com.
  3. ^ “What Is a Creatinine Blood Test? Low & High Ranges”. Medicinenet.com. Retrieved 21 September 2018.
  4. ^ Jump up to:
    a b c d e Taylor, E. Howard (1989). Clinical Chemistry. New York: John Wiley and Sons. pp. 4, 58–62.
  5. ^ Allen PJ (May 2012). “Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?”. Neurosci Biobehav Rev. 36 (5): 1442–62. doi:10.1016/j.neubiorev.2012.03.005. PMC 3340488. PMID 22465051.
  6. ^ Shemesh O, Golbetz H, Kriss JP, Myers BD (November 1985). “Limitations of creatinine as a filtration marker in glomerulopathic patients”. Kidney Int. 28 (5): 830–8. doi:10.1038/ki.1985.205. PMID 2418254.
  7. ^ Hosten, Adrian O. (1990). Walker, H. Kenneth; Hall, W. Dallas; Hurst, J. Willis, eds. Clinical Methods: The History, Physical, and Laboratory Examinations (3rd ed.). Boston: Butterworths. ISBN 978-0409900774. PMID 21250147.
  8. ^ McDonald, Thomas; Drescher, Kristen M.; Weber, Annika; Tracy, Steven (1 March 2012). “Creatinine inhibits bacterial replication” (PDF). The Journal of Antibiotics. 65 (3): 153–156. doi:10.1038/ja.2011.131. PMID 22293916.
  9. ^ Smithee, Shane; Tracy, Steven; Drescher, Kristen M.; Pitz, Lisa A.; McDonald, Thomas (1 October 2014). “A novel, broadly applicable approach to isolation of fungi in diverse growth media”. Journal of Microbiological Methods. 105: 155–161. doi:10.1016/j.mimet.2014.07.023. PMID 25093757.
  10. ^ Leland, Korey M.; McDonald, Thomas L.; Drescher, Kristen M. (1 September 2011). “Effect of creatine, creatinine, and creatine ethyl ester on TLR expression in macrophages”. International Immunopharmacology. 11 (9): 1341–1347. doi:10.1016/j.intimp.2011.04.018. PMC 3157573. PMID 21575742.

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