Editing Creatinine (section)

==Biological relevance==
[[Serum (blood)|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).<ref>{{cite web|url=http://www.medicinenet.com/creatinine_blood_test/article.htm|title=What Is a Creatinine Blood Test? Low & High Ranges|website=Medicinenet.com|access-date=21 September 2018|archive-date=21 September 2018|archive-url=https://web.archive.org/web/20180921230201/https://www.medicinenet.com/creatinine_blood_test/article.htm|url-status=live}}</ref>

Creatine is synthesized primarily in the liver by methylation of [[glycocyamine]] (guanidino acetate, synthesized in the kidney from the [[amino acid]]s [[arginine]] and [[glycine]]) by [[S-adenosyl methionine]]. It is then transported in the blood to other organs, muscles, and the brain, where it is [[phosphorylation|phosphorylated]] to phosphocreatine, a high-energy compound.<ref name=ClinChem89 /> Creatine conversion to phosphocreatine is catalysed by [[creatine kinase]]; spontaneous formation of creatinine occurs during the reaction.<ref name="CreatineSupp">{{cite journal | vauthors = Allen PJ | title = Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value? | journal = Neuroscience and Biobehavioral Reviews | volume = 36 | issue = 5 | pages = 1442–62 | date = May 2012 | pmid = 22465051 | pmc = 3340488 | doi = 10.1016/j.neubiorev.2012.03.005 }}</ref>

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 [[Renal function#Creatinine Clearance CCr|creatinine clearance]] (CrCl), which correlates approximately with the [[glomerular filtration rate]] (GFR). Blood creatinine concentrations may also be used alone to calculate the estimated 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.<ref>{{cite journal | vauthors = Shemesh O, Golbetz H, Kriss JP, Myers BD | title = Limitations of creatinine as a filtration marker in glomerulopathic patients | journal = Kidney International | volume = 28 | issue = 5 | pages = 830–8 | date = November 1985 | pmid = 2418254 | doi = 10.1038/ki.1985.205 | doi-access = free }}</ref> [[Ketoacid]]s, [[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]].)<ref>{{Cite journal |last=Uemura |first=O |last2=Ishikura |first2=K |last3=Kamei |first3=K |last4=Hamada |first4=R |last5=Yamamoto |first5=M |last6=Gotoh |first6=Y |last7=Fujita |first7=N |last8=Sakai |first8=T |last9=Sano |first9=T |last10=Fushimi |first10=M |last11=Iijima |first11=K |date=2022 |title=Comparison of inulin clearance with 2-h creatinine clearance in Japanese pediatric patients with renal disease: open-label phase 3 study of inulin. |journal=Clin Exp Nephrol |volume=26 |issue=2 |pages=132-9 |via=PubMed}}</ref><ref>{{Cite journal |last=Toto |first=RD |date=1995 |title=Conventional measurement of renal function utilizing serum creatinine, creatinine clearance, inulin and para-aminohippuric acid clearance. |journal=Curr Opin Nephrol Hypertens |volume=4 |issue=6 |pages=505-9 |via=PubMed}}</ref>

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.<ref>{{cite journal | vauthors = Henderson GC, Dhatariya K, Ford GC, Klaus KA, Basu R, Rizza RA, Jensen MD, Khosla S, O'Brien P, Nair KS | display-authors = 6 | title = Higher muscle protein synthesis in women than men across the lifespan, and failure of androgen administration to amend age-related decrements | journal = FASEB Journal | volume = 23 | issue = 2 | pages = 631–41 | date = February 2009 | pmid = 18827019 | pmc = 2630787 | doi = 10.1096/fj.08-117200 | doi-access = free }}</ref> As HDL supports muscle anabolism, higher muscle protein turnover links increased creatine to the generally higher serum HDL in women compared with serum HDL in men and the HDL associated benefits, such as reduced incidence of cardiovascular complications and reduced [[COVID-19]] severity.<ref name="pmid15976321">{{cite journal | vauthors = Lewis GF, Rader DJ | title = New insights into the regulation of HDL metabolism and reverse cholesterol transport | journal = Circulation Research | volume = 96 | issue = 12 | pages = 1221–32 | date = June 2005 | pmid = 15976321 | doi = 10.1161/01.RES.0000170946.56981.5c | s2cid = 2050414 }}</ref><ref name="pmid24170386">{{cite journal | vauthors = Lehti M, Donelan E, Abplanalp W, Al-Massadi O, Habegger KM, Weber J, Ress C, Mansfeld J, Somvanshi S, Trivedi C, Keuper M, Ograjsek T, Striese C, Cucuruz S, Pfluger PT, Krishna R, Gordon SM, Silva RA, Luquet S, Castel J, Martinez S, D'Alessio D, Davidson WS, Hofmann SM | display-authors = 6 | title = High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice | journal = Circulation | volume = 128 | issue = 22 | pages = 2364–71 | date = November 2013 | pmid = 24170386 | pmc = 3957345 | doi = 10.1161/CIRCULATIONAHA.113.001551 }}</ref><ref name="pmid33785815">{{cite journal | vauthors = Masana L, Correig E, Ibarretxe D, Anoro E, Arroyo JA, Jericó C, Guerrero C, Miret M, Näf S, Pardo A, Perea V, Pérez-Bernalte R, Plana N, Ramírez-Montesinos R, Royuela M, Soler C, Urquizu-Padilla M, Zamora A, Pedro-Botet J | display-authors = 6 | title = Low HDL and high triglycerides predict COVID-19 severity | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 7217 | date = March 2021 | pmid = 33785815 | pmc = 8010012 | doi = 10.1038/s41598-021-86747-5 | bibcode = 2021NatSR..11.7217M }}</ref>

===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 [[Antimicrobial resistance|antibiotic-resistant]] bacterial strains.<ref>{{cite journal | vauthors = McDonald T, Drescher KM, Weber A, Tracy S | title = Creatinine inhibits bacterial replication | journal = The Journal of Antibiotics | volume = 65 | issue = 3 | pages = 153–156 | date = March 2012 | pmid = 22293916 | doi = 10.1038/ja.2011.131 | doi-access = free }}</ref> 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 [[Immunosuppression|immunosuppressive]] properties.<ref>{{cite journal | vauthors = Smithee S, Tracy S, Drescher KM, Pitz LA, McDonald T | title = A novel, broadly applicable approach to isolation of fungi in diverse growth media | journal = Journal of Microbiological Methods | volume = 105 | pages = 155–61 | date = October 2014 | pmid = 25093757 | doi = 10.1016/j.mimet.2014.07.023 }}</ref><ref>{{cite journal | vauthors = Leland KM, McDonald TL, Drescher KM | title = Effect of creatine, creatinine, and creatine ethyl ester on TLR expression in macrophages | journal = International Immunopharmacology | volume = 11 | issue = 9 | pages = 1341–7 | date = September 2011 | pmid = 21575742 | pmc = 3157573 | doi = 10.1016/j.intimp.2011.04.018 }}</ref>