Dxylose Testing.docx

Dxylose Testing.docx

《Dxylose Testing.docx》由会员分享，可在线阅读，更多相关《Dxylose Testing.docx（16页珍藏版）》请在冰豆网上搜索。

DxyloseTesting

D-xyloseTesting

ournalofClinicalGastroenterology

Issue:

Volume29

（2）, September1999, pp143-150

Craig,RobertM.M.D.;Ehrenpreis,EliD.M.D.

AuthorInformation

FromtheDivisionofGastroenterology/Hepatology（R.M.C.）,DepartmentofMedicine,NorthwesternUniversityMedicalSchool,Chicago,IL;andtheDivisionofGastroenterology（E.D.E.）,DepartmentofMedicine,UniversityofChicagoMedicalSchool,IL.

AddresscorrespondencestoDr.RobertM.Craig,NorthwesternUniversityMedicalSchool,Searle10-541,303E.Chicago,Chicago,IL60611.

Abstract 

TheliteratureonD-xylosetestinghasbeenreviewed,stressingadvancesinourunderstandingofabsorptioningeneral（includingD-xyloseabsorption）,therelationshipofD-xylosetestingtothedevelopmentofexcellentserologictestsforthediagnosisofceliacdisease,theuseofD-xylosetestingintheevaluationofdiarrheainacquiredimmunodeficiencysyndrome,newinformationonbreathtestingfortheevaluationofmalabsorption,andrecentinformationontheunderstandingofD-xyloseabsorptioncomparedwithtranscellularvs.paracellulartransport.TheauthorssuggestwaysinwhichD-xylosetestingmightbeemployedinmalabsorptionordiarrheaevaluations,includingsomealgorithms. 

SinceourlastreviewonD-xylosetesting,1 therehavebeenadvancesinourunderstandingofabsorptioningeneral,includingD-xyloseabsorption,thedevelopmentofexcellentserologictestsforthediagnosisofceliacdisease,theuseofD-xylosetestingintheevaluationofdiarrheainacquiredimmunodeficiencysyndrome（AIDS）,newinformationonbreathtestingfortheevaluationofmalabsorption,andnewinformationontheunderstandingofD-xyloseabsorptioncomparedwithtranscellularvs.paracellulartransit.WehavereviewedtheliteratureonD-xylosetestingandrelatepastunderstandingtothenewerdevelopments. 

BacktoTop 

PHYSIOLOGY,CHEMISTRY,ANDKINETICSOFABSORPTION 

D-xyloseisapentosefoundnaturallyinplants.2 Itsincompleteabsorptionallowsittobeusedasanabsorptivetest.Othermonosaccharidesareabsorbedmuchmoreavidly,evenwhenthesmallintestineisabnormal.3 Itisabsorbedunchangedfromthesmallintestine,4,5 andapproximately30%ismetabolizedbythelivertocarbondioxide（CO2）andthreitol.6,7 Inaddition,5%oftheabsorbeddoseisexcretedunchangedinthebileandundergoesenterohepaticcycling.8Theremainderisexcretedintheurine,allowingforitsuseinclinicaltesting. 

RecentlywehaveusedakineticmodelofD-xyloseabsorptioninanattempttocharacterizesmallbowelabsorptionphysiologically （Fig.1）.9-15 Byusingintravenousandoraldosingfollowedbyfrequentsamplingofthebloodandurine,weareabletoshowthatD-xyloseisdistributedprimarilyintheextracellularspace.Approximatelyhalfoftheintravenouslyadministereddoseisexcretedbythekidneys,andtheremaininghalfisexcretedbynonrenal,presumablyhepatic,mechanisms.Withthedeconvolutionoftheoraldosingcurve,utilizingthedistributionandexcretioncharacteristicsfromtheintravenouscurve,wecancharacterizetheabsorptionkineticsintermsofrateconstants:

Ka,theabsorptionconstantforD-xyloseabsorption,andKo,thekineticparameterfornonabsorptivegastrointestinallosses.ThebioavailabilityofD-xylosecanbecalculatedbytheratioofKa/Ka+Ko.Normalsubjectsabsorbapproximately70%ofa25-goraldose.9 WefoundthatKacorrelatescloselywiththe1-hourserumconcentrationofD-xylose（r =0.74, p =5.0×10-4）,andthatthe5-hoururinecontentofD-xylosecorrelatescloselywithitsabsolutebioavailability,F（r =0.93,p <1×10-6）.11

Fig.1

Innormalindividualsapproximately70%absorptionofa25-gdose,withapproximately50%renalexcretion,yields8.75grenalexcretion,puttingitintherangeofnormal5-hoururinaryD-xylosecontentafter25-gdosing.Essentiallyalloftheabsorption,metabolism,andexcretionoccurwithinthefirst5hoursafteradministration.11 Theacceptedlowerlimitofnormalforthe5-hoururinecontentinpatientswithnormalrenalfunctionis4g.11 Theacceptedlowerlimitofnormalforthe1-hourserumD-xyloseconcentrationforthosewithcreatinineclearancegreaterthan30mL/minis25mg/dL.9-11 

ThemechanismofD-xyloseenterocyteabsorptioniscontroversial.StudiesinnormalmicrovillousvesiclessupportpassiveabsorptionasthepredominantmechanismofD-xyloseabsorption.16 Inaddition,intestinalperfusionstudiesinnormalhumanshaveshownthatD-xyloseisabsorbedpassively,althoughtheconcentrationsemployedinthesestudieswerelowerthanthoseusedinstandardD-xylosetesting.16 Asaturableelementmayhavebeenobservedwithhigherconcentrations.Earlierintestinalperfusionstudiesalsosuggestedasmall,saturablecomponenttoD-xyloseabsorption.5 PassiveabsorptionofD-xylosedoesnotdependoncarrier-mediatedMichaelis-Mentonkinetics,andtherateconstantforabsorptionshouldnotchangewithdifferentdosesofD-xylose.ThekineticsofD-xyloseabsorptionforthe25-and15-gdosesinpatients,mostlywithsmallintestinalmalabsorption,havebeencompared.12 Therateconstantforabsorption,Ka,wasslightlyhigherinthosewiththelowerdose,suggestingsomecomponentofactiveabsorption.However,thesedataoverallsupportpredominantlypassiveabsorption-transcellularorparacellular-withlittleornocarrier-mediatedtransport.AlthoughdatahavebeenpublishedwithvaryingdosesofD-xylose,thereareonlyformalkineticstudieswiththe25-and15-gdoses.9-15Thesesupporttheclinicalutilityofthelowerlimitofnormalforthe5-hoururineD-xylosecontentinpatientswithnormalrenalfunctionof4gforthe25-gdoseand2.5gforthe15-gdose;andthelowerlimitofnormalforthe1-hourserumD-xyloseof25mg/dLforeitherthe25-or15-gdoseforpatientswithcreatinineclearance>30mL/min.10,12 Preliminarydatainourlaboratoryshowthatthe15-gdosemaybeusedinanephricpatientsandthatthelowerlimitofnormalforthe1-hourserumD-xyloseconcentrationis20mg/dL（R.M.Craig,unpublishedobservations）. 

BacktoTop 

USEOFD-XYLOSETESTINGINPEDIATRICS,GERIATRICS,ANDVARIOUSDISEASESTATES 

TheuseofserumratherthanurinaryD-xylosetestinginpediatricsisfavoredduetodifficultiesinobtainingaccuratelytimedurinecollections,especiallyinveryyoungchildrenandinfants.17,18 BecauseD-xyloseabsorptionandexcretionincreaseduringthefirstyearoflife,19,20 somemodificationofnormallevelsisrequired.Forchildrenlessthan12yearsold,wehavesuggestedthatalowerlimitofnormalforthe1-hourserumD-xyloseconcentrationshouldbe15mg/dLaftera5-gdose.1 Usingadoseof15g/m2 forinfantsorchildrenlessthan6monthsofageisappropriate,withthelowerlimitofnormalagainbeing15mg/dL.21-23 

SomestudieshaveindicatedthataserumendomysialantibodyismoresensitiveandspecificthaneithertheserumorurineD-xylosetestindiagnosingceliacdiseaseinchildren.24 Othershavereportedonlya67%predictionaccuracyofD-xylosetestingininfantswithbiopsy-provedduodenalatrophy.25 AnovelironabsorptiontesthasalsobeenshowntobesuperiortotheD-xylosetestinonegroupofchildrenwithceliacdiseaseandothersmallintestinalabsorptivedefects.26 

ThereisapparentlynoinherentdiminutioninD-xyloseabsorptionintheelderlyifrenalfunctionisaddressedappropriately.27-29 Thishasalsobeenconfirmedwithpharmacokineticanalysisinelderlypatients.30,31 

AppropriatetestingconditionsarerequiredbecauseseveralfactorsmayaltertheinterpretationofD-xylosetesting.Thetestingshouldbedonefastingbecausetheremaybeacomponentoffacilitatedabsorptionfromglucose,andmeatorfibermightdiminishD-xyloseabsorption.32,33 Prokineticandantimotilityagentsshouldprobablybeavoidedaswell. 

Thevalueofcombiningthe1-hourserumconcentrationandthe5-hoururinecontentofD-xyloseisunderscoredbytheexamplesofdelayedgastricemptyingandintestinalhurry.IntestinalhurrymightdiminishbioavailabilityofD-xylose,reflectedclinicallyinalowerthanexpected5-hoururinaryD-xylosetest.Thisobservationisconfirmedbythedecreasedbioavailabilityseenwiththe25-gdoseoverthe15-gdose,9,12 presumablyduetoosmoticeffectsfromthelargerdose.However,the1-hourserumD-xylose（ortherateconstantforabsorption）isnotaffectedsignificantlybyamodifieddose,9,12 andwillbenormalinpatientswithdiarrheadueonlytointestinalhurry. 

Diminishedgastricemptyingmightbeexpectedtoyieldalow1-hourserumD-xyloseandadiminishedrateconstantforabsorption,Ka.34 However,thebioavailabilitymightstillbenormal,unlesstheD-xyloseneverleavesthestomach.Thenormalbioavailabilityunderthesecircumstanceswouldbereflectedclinicallyinanormal5-hoururinaryD-xylosecontent. 

PortalhypertensionwouldbeexpectedtobeassociatedwithdiminishedD-xylosebioavailabilityduetosplanchniccongestion,asseeninonestudyindogs.35 However,theremightbediminishedhepaticmetabolismduetoshuntingaroundtheliverordecreasedhepaticfunction,yieldinghigherthanexpectedurinaryorserumvalues.Onestudyof25cirrhoticpatientsshowednormalD-xyloseabsorption.36 DiminishedexcretionofD-xylosemightbeexpectedwiththepresenceofascitesbecauseD-xyloseisdistributedininterstitialspace,includingascites.37 FormalkineticevaluationsofD-xylosedistributionandabsorptionhavenotbeenperformedinthispatientgroup. 

TherearesomedatathatindicatethediminishedexcretionorabsorptionofD-xylosemightensuefromtheuseofnonsteroidalanti-inflammatoryagentsoraspirin,38 and