Jaffe reaction: Difference between revisions
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{{Infobox scientist |
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|name = Max Jaffe |
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|image = Max Jaffe.jpg |
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|image_size = 200px |
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|quotation= |
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|birth_date = 25 July 1841 |
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|birth_place = Grünberg, [[Silesia]] |
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|residence = |
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|nationality = German |
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|death_date = 26 October 1911 |
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|death_place = [[Berlin]], [[Germany]] |
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|field = [[Biochemistry]], [[Pathology]], [[Pharmacology]] |
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|work_institutions = [[University of Königsberg]] |
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|alma_mater = [[University of Berlin]] |
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|doctoral_advisor = |
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|doctoral_students = |
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|known_for = ''Jaffe reaction'' of [[creatinine]] and [[picric acid]]—the oldest clinical methodology still in use. |
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|prizes = |
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|religion = |
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|footnotes = |
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|signature = |
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}} |
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The '''Jaffe reaction''' is a [[colorimetry|colorimetric]] method used in [[clinical chemistry]] to determine [[creatinine]] levels in blood and urine. In 1886, '''Max Jaffe''' (1841-1911) wrote about its basic principles in the paper ''Über den Niederschlag, welchen Pikrinsäre in normalem Harn erzeugt und über eine neue Reaction des Kreatinins'' in which he described the properties of creatinine and [[picric acid]] in an [[alkaline]] [[solution]]. The color change that occurred was [[directly proportional]] to the [[concentration]] of creatinine, however he also noted that several other [[organic compound]]s induced similar reactions. In the early 20th century, [[Otto Folin]] adapted Jaffe's research into a clinical procedure. The Jaffe reaction, despite its nonspecificity for creatinine, is still widely employed as the method of choice for creatinine testing<ref name=ClinBioChem>{{cite book|last=Ahmed|first=Nessar|title=Clinical Biochemistry|year=2011|publisher=Oxford University Press|location=New York|page=72}}</ref> due to its speed, adaptability in automated analysis, and cost-effectiveness, and is the oldest [[methodology]] continued to be used in the [[medical laboratory]]<ref name=ClinChem89>{{cite book|last=Taylor|first=E. Howard|title=Clinical Chemistry|year=1989|publisher=John Wiley and Sons|location=New York|pages=4, 58-62}}</ref>. It is this nonspecificity that has motivated the development of new reference methods for creatinine analysis into the 21st century. |
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==Max Jaffe== |
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Max Jaffe was a distinguished<ref name=NDT-ref3>{{cite book|last=Pagel|first=J.|title=Biographisches Lexikon hervorragender Ärzte des neunzehnten Jahrhunderts|year=1901|url=http://www.zeno.org/Pagel-1901/A/Jaff%C3%A9,+Max|publisher=Urban & Schwarzenberg|location=Berlin|page=814|accessdate=October 19, 2012}}</ref> 19th-century German [[biochemist]], [[pathologist]], [[pharmacologist]], and professor.<ref name=NDT>{{cite journal|last=Delanghe|first=Joris R. and Marijn Speeckaert|title=Creatinine determination according to Jaffe—what does it stand for?|journal=Nephrology Dialysis Transplantation Plus|year=2011|issue=0|pages=1-4|url=http://ckj.oxfordjournals.org/content/4/2/83.full.pdf|accessdate=October 19, 2012}}</ref> He was born of Jewish descent on July 25, 1841, in what was formerly Grünberg, [[Silesia]] and is now [[Zielona Góra]], [[Poland]].<ref name=NDT /> While attending medical school at the [[University of Berlin]], he studied under [[Ludwig_Traube_(physician)|Ludwig Traube]] and [[Wilhelm Kühne]].<ref name=NDT /> Afterward, he worked as an assistant in a medical clinic in [[Königsberg]].<ref name=NDT /> There, he co-authored a paper on putrid [[sputum]] with [[Ernst Viktor von Leyden]] that led to the discovery of certain characteristic putrid processes in the [[lung]]s.<ref name=NDT /> After earning his degree in [[internal medicine]], he served in the [[Franco-Prussian War]] and was decorated with the [[Iron Cross]] Second Class.<ref name=NDT /> The title of ''Extraordinary Professor of Medicinal Chemistry'' was awarded to him in 1872 and the following year he became the first ''Ordinary Professor of Pharmacology'' at the [[University of Königsberg]].<ref name=NDT /> He was promoted to director of the ''Laboratory for Medical Chemistry and Experimental Pharmacology'' in 1878 and became a member of the ''Deutsche Akademie der Naturforscher Leopoldina'' in 1882.<ref name=NDT /> Aside from studying creatinine, he is also known for discovering [[urobilin]] and [[urobilinogen]] in [[urine]] and found that these compounds originated in [[bile]].<ref name=NDT /> He died on October 26, 1911 in Berlin and is buried in the [[Weißensee Cemetery]].<ref name=NDT /> |
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===''"...eine neue Reaction des Kreatinins"''=== |
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Creatinine was first synthesized ''[[in vitro]]'' by [[Ivan Horbaczewski]] in 1885.<ref name=NDT /> One year later, Jaffe's research was published in the paper ''Über den Niederschlag, welchen Pikrinsäre in normalem Harn erzeugt und über eine neue Reaction des Kreatinins''.<ref name=Jaffe>{{cite journal|last=Jaffe|first=M.|title=Über den Niederschlag, welchen Pikrinsäre in normalem Harn erzeugt und über eine neue Reaction des Kreatinins|journal=Zeitschrift für physiologische Chemie|year=1886|volume=10|issue=5|pages=391-400|url=http://vlp.mpiwg-berlin.mpg.de/library/data/lit16635?}}</ref> Jaffe had noticed that, when mixed in a [[sodium hydroxide]] (NaOH) solution, picric acid and creatinine formed a reddish-orange color and needle-like crystal [[Precipitation (chemistry)|precipitate]].<ref name=NDT /><ref name=ClinChem56>{{cite book|last=Annino|first=Joseph S.|title=Clinical chemistry, principles and procedures|year=1956|edition=first|publisher=Little, Brown and Company|location=Boston|page=235-241}}</ref><ref name=Greenwald2>{{cite journal|last=Greenwald|first=Isidore|title=The chemistry of Jaffe's reaction for creatinine II. The effect of substitution in the creatinine molecule and a possible formula for the red tautomer|journal=Journal of the American Chemical Society|year=1925|volume=47|issue=5|pages=1443-1448|accessdate=October 22, 2012}}</ref> By using [[zinc chloride]] in a process known as the ''Neubauer reaction'', and then performing the [[Theodor Weyl|Weyl's test]], a colorimetric reaction using [[sodium nitroprusside]] (SNP), he determined that the precipitated compound was a double [[salt (chemistry)|salt]] of the solution.<ref name=Greenwald2 /> Although he found the amount of precipitate directly proportional to the creatinine concentration, he also noted that the reaction was highly nonspecific and could be observed with many other organic compounds.<ref name=NDT /><ref name=ClinChem56 /> |
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==Clinical applications== |
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{| style="width: 25%; border: 1px solid darkgray; float: right" " cellpadding="5" |
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|- |
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| colspan="3" style="background: #ffffc0;" border="0" align="center" | Blood sample information for creatinine assays<br /> |
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based on the Jaffe reaction.<ref name=ClinChem89 /> |
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|- style="background: #d0d0ff;" align="center" |
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| width="15%" | |
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| width="40%" | Serum |
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| width="45%" | Plasma |
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|- valign="top" |
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| style="background: #d0d0ff;" align="center" | Non-interfering Anticoagulants |
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| style="background: #dfdfdf;" | |
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| align="left" | |
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* <small>Sodium heparin</small> |
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* <small>Potassium heparin</small> |
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* <small>Lithium heparin</small> |
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* <small>EDTA</small> |
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|- valign="top" |
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| style="background: #d0d0ff;" align="center" | Interferents |
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| align="left" colspan="2" | |
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* <small>Hemolysis - ''falsely increases result.''</small> |
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* <small>Icteremia - ''falsely decreases result.''</small> |
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* <small>Lipemia - ''falsely decreases result.''</small> |
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* <small>Ammonium heparin - ''falsely increases result.''</small> |
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* <small>Non-specific chromogens such as protein, glucose, acetoacetate, ascorbic acid, cephalosporins, ammonium - ''falsely increase results.''</small> |
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|- |
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|} |
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Although Jaffe's name is synonymous with clinical creatinine testing, his paper only described the principle behind what would later become the enduring method.<ref name=NDT /> It was Otto Folin (1867-1934), a [[Harvard]] biochemist, who adapted Jaffe's research—abandoning the standard Neubauer reaction of the time—and published several papers using the Jaffe reaction to analyze creatinine levels in both blood and urine.<ref name=Folin1914>{{cite journal|last=Folin|first=Otto|coauthors=J. L. Morris|title=On the determination of creatinine and creatine in urine|journal=Journal of Biological Chemistry|year=1914|issue=17|pages=469-473|accessdate=10/19/2012}}</ref><ref name=Folin>{{cite journal|last=Shaffer|first=Philip|title=Otto Folin (1867-1934)|journal=National Academy of Sciences|year=1952|url=http://www.nasonline.org/publications/biographical-memoirs/memoir-pdfs/folin-otto.pdf|volume=27|pages=47-82|accessdate=October 20, 2012}}</ref><ref name=Folin1919>{{cite journal|last=Folin|first=Otto|coauthors=H. Wu|title=A System of Blood Analysis|journal=Journal of Biological Chemistry|year=1919|volume=38|issue=1|pages=81-110|url=http://books.google.com/books/reader?id=lo4WAAAAIAAJ&lr=&printsec=frontcover&output=reader&pg=GBS.PA81|accessdate=October 19, 2012}}</ref> Folin began using the picric acid procedure in 1901 and included it in his 1916 ''Lab Manual of Biological Chemistry''.<ref name=Folin /><ref name=FolinLab>{{cite book|last=Folin|first=Otto|title=Lab Manual of Biological Chemistry|year=1916|publisher=D. Appleton and Co.|location=New York|pages=171-173|url=http://play.google.com/books/reader?id=hZIsAAAAYAAJ&printsec=frontcover&output=reader&authuser=0&hl=en&pg=GBS.PA171}}</ref> During his career, Folin modified and improved several quantitative colorimetric procedures, the first of which was for creatinine.<ref name=Folin /> He took advantage of technology available at the time, using a [[Jules Duboscq|Duboscq]] [[Colorimeter (chemistry)|colorimeter]] for measurement precision, and is credited for introducing colorimetry into modern biochemical analysis.<ref name=Folin /> |
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It should be noted that Folin's research did not focus on creatinine as a renal function indicator. Since the precursors of creatinine are synthesized in the liver<ref name=ClinChem89 />, at this point in history, creatinine was considered indicative of liver function.<ref name=NDT /> It was not until 1926 that Poul Kristian Brandt Rehberg suggested creatinine was a significant marker for [[renal function]].<ref name=NDT /> |
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===Interfering chromogens=== |
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The nonspecificity of Jaffe's reaction causes falsely elevated creatinine results in the presence of [[protein]], [[glucose]], [[acetoacetate]], [[ascorbic acid]], [[guanidine]], [[acetone]], [[cephalosporins]], [[ketone bodies]], α-[[keto acids]], and other organic compounds.<ref name=ClinBioChem /><ref name=ClinChem89 /> [[Ammonium]] is also an interferent; if the sample is [[blood plasma|plasma]], care needs to be taken that ammonium [[heparin]] has not been used as an [[anticoagulant]].<ref Name=ClinChem89 /> Nonspecificity is markedly decreased in urine samples since urine creatinine levels are much higher than blood and it generally does not contain significant levels of interfering chromogens.<ref name=ClinChem89 /><ref name=ClinChem56 /> |
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The Jaffe reaction's nonspecificity remains an important issue.<ref name=ClinBioChem /> Diabetes patients are a high-risk population to develop [[chronic kidney disease]] (CKD) and, therefore, interferences from glucose and acetoacetate are of particular importance.<ref name=JCC>{{cite journal|last=Myers|first=Gary L. et al|title=Recommendations for Improving Serum Creatinine Measurement: A Report from the Laboratory Working Group of the National Kidney Disease Education Program|journal=Clinical Chemistry|year=2006|volume=52|issue=1|pages=5-18|url=http://www.clinchem.org/content/52/1/5.full.pdf|accessdate=October 22, 2012}}</ref> |
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Artifacts such as [[hemolysis]], [[lipemia]], and icteremia can also affect accuracy. Hemolysis releases Jaffe-reacting chromogens and therefore will falsely increase results.<ref name=ClinChem89 /> Lipemia and icteremia can inhibit optical readings and falsely decrease values.<ref name=ClinChem89 /> The procedure has developed over time with the intention to minimize these interferents.<ref name=ClinBioChem /> |
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===From Neubauer to SRM 967=== |
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Before Jaffe, Neubauer described a similar precipitation reaction by mixing creatinine with zinc chloride (ZnCl<sub>2</sub>) and performing a Weyl's test—the addition of SNP to NaOH and then incubating with [[acetic acid]] (CH<sub>3</sub>CO<sub>2</sub>H) to develop a color change.<ref name=NDT /> Until Folin developed Jaffe's reaction into a clinical procedure, Neubauer's method was how creatinine was measured. As Folin's method evolved, various techniques were implemented to remove Jaffe-reacting substances, mostly protein, from the sample and increase specificity.<ref name=ClinChem56 /> By the 1950's, precipitated [[aluminum silicate]], called Lloyd's reagent<ref>{{cite web|title=Lloyd reagent|url=http://www.medilexicon.com/medicaldictionary.php?t=76306|work=mediLexicon|accessdate=October 22, 2012}}</ref>, was being used to remove protein from [[serum (blood)|serum]], further improving accuracy.<ref name=ClinChem92>{{cite book|last=Bishop|first=Michael L.|title=Clinical Chemistry: Principles and Correlations|year=1992|publisher=J. B. Lippincott and Company|location=Philadelphia|pages=441|edition=second}}</ref> [[Fuller's earth]] was also used for protein-binding<ref name=ClinChem89 />, but the reference method until the 1980's was adsorption with Lloyd's reagent.<ref name=Mitchell>{{cite journal|last=Mitchell|first=Robert J.|title=Improved Method for Specific Determination of Creatinine in Serum and Urine|journal=Clinical Chemistry|year=1973|volume=19|issue=4|pages=408-410|url=http://www.clinchem.org/content/19/4/408.full.pdf|accessdate=October 22, 2012}}</ref>. New concerns arose due to non-standardization of procedures; different labs were reading results at different endpoints.<ref name=NDT /> This problem was resolved with the advent of [[automated analyzer]]s in the 1960's and 1970's, which introduced a kinetic reading of results rather than a specific endpoint.<ref name=ClinBioChem /> Kinetic Jaffe methods involve mixing serum with alkaline picrate and reading the rate of change in absorption [[spectrophotometer|spectrophotometrically]] at 520 nm.<ref name=ClinChem92 /> This not only standardized the procedure, but also removed the need for sample deproteinization.<ref name=NDT /> It also introduced two new problems—analyzers used an algorithmic compensation to correct for pseudochromogens, and calibrations were not yet standardized between instruments.<ref name=ClinBioChem /><ref name=NDT /> |
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The 1980's saw several new technologies that promised to change the way creatinine testing was done. Enzymatic and ion-exchange methods provided better accuracy but had other drawbacks.<ref name=ClinChem89 /><ref name=NDT /><ref name=Mitchell /> Enzymatic methods reduced some interferences but other new ones were discovered.<ref name=JCC /> [[High-performance liquid chromatography]], HPLC, was more sensitive and specific, and had become the new reference method endorsed by the [[American Association for Clinical Chemistry]].<ref name=ClinChem89 /><ref name=JCC /><ref name=ClinChem92 /> HPLC addressed the shortcomings of Jaffe-based methods, but was labor-intensive, expensive, and therefore impractical for routine analysis of the most frequently ordered renal analyte in medical labs.<ref name=ClinChem89 /> Simple, easily automated and cost-effective, Jaffe-based methods have persisted into the 21st century, despite their imperfections.<ref name=ClinBioChem /> |
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By 2006, [[isotope dilution mass spectrometry]] (IDMS) became the reference method.<ref name=ClinBioChem /><ref name=JCC /> To improve the accuracy in creatinine testing, new standards were developed by the [[National Institute of Standards and Technology]] (NIST).<ref name=NIST>{{cite web|work=National Institute of Standards and Technology|title=New Reference Material for Diagnosing Kidney Disease|url=http://www.nist.gov/public_affairs/techbeat/tb2007_0316.htm#srm|accessdate=October 22, 2012}}</ref> The [[College of American Pathologists]] (CAP) and the National Kidney Disease Education Program (NKDEP) collaborated with NIST to develop a new control reference called ''standard reference material 967'' (SRM 967).<ref name=NIST /> SRM 967 aims to standardize calibration of creatinine testing, including Jaffe methods.<ref name=NIST /> Use of both IDMS and SRM 967 are currently recommended by the National Institutes of Health.<ref name=NIH>{{cite web|title=Creatinine Standardization Recommendations|url=http://nkdep.nih.gov/lab-evaluation/gfr/creatinine-standardization/recommendations.shtml|work=National Institutes of Health|accessdate=October 22, 2012}}</ref> |
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==Works== |
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* [http://vlp.mpiwg-berlin.mpg.de/library/data/lit16635? ''Über den Niederschlag, welchen Pikrinsäre in normalem Harn erzeugt und über eine neue Reaction des Kreatinins''] by Max Jaffe (1886) |
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==See also== |
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* [[Creatinine]] — the most commonly ordered clinical test to determine renal function.<br /> |
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* [[Otto Folin]] — developed the Jaffe reaction into its clinical application. |
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==References== |
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{{reflist|2}} |
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==Further reading== |
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* [http://books.google.com/books/reader?id=lo4WAAAAIAAJ&lr=&printsec=frontcover&output=reader&pg=GBS.PA81 ''A System of Blood Analysis''] by Folin and Wu (1919)<br /> |
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* [http://www.jbc.org/content/17/4/469.full.pdf ''On the determination of creatinine and creatine in urine''] by Otto Folin (1914) |
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* [http://www.clinchem.org/content/52/1/5.full.pdf ''Recommendations for Improving Serum Creatinine Measurement: A Report from the Laboratory Working Group of the National Kidney Disease Education Program''] by Gary L. Myers et al (2006) |
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* {{cite journal | doi = 10.1038/148110d0 | title = Max Jaffé (1841–1911) | year = 1941 | journal = Nature | volume = 148 | issue = 3743 | pages = 110}} |
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==Categories== |
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[[Category:Biochemistry methods]] |
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[[Category:Biochemists]] |
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[[Category:Clinical biochemistry]] |
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