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Oreopoulos,3MartinSchreiber,12andRobertSoderbloom13 1m݌   Ќ       S5  2     UniversityofWesternOntario,1London;McMasterUniversity,2Hamilton;Universityof 5  Toronto,3Toronto,Ontario,Canada;BowmanGraySchoolofMedicine,4WinstonMSalem, ! q NorthCarolina;UniversityofIllinoisatChicago,5Chicago,Illinois;UniversityofCalifornia,6  ]  Sacramento,California;IndianaUniversity,7Indianapolis,Indiana;UniversityofTexas I  SouthwesternMedicalCenter,8Dallas,Texas;RushPresbyterianSt.Luke'sMedicalCenter,9 5  Chicago,Illinois;BaxterHealthcareCorporation,10McGawPark,Illinois;Universityof !  Missouri,11Columbia,Missouri;ClevelandClinic,12Cleveland,Ohio;LomaLindaUniversity   SchoolofMedicine,13LomaLinda,California,U.S.A.reviewsandoriginalarticles 8݌   Ќ       S;8      DatafromtheCanadaMU.S.A.(CANUSA)Studyhaverecentlyconfirmedalongsuspected ; linkagebetweentotalclearanceandpatientsurvivalinperitonealdialysis(PD).Recognizingthat 'w whatwehavehistoricallyacceptedasadequatePDsimplyisnot,theAdHocCommitteeon c PeritonealDialysisAdequacymetinJanuary,1996.Thiscommitteeofinvitedexpertswas O convenedbyBaxterHealthcareCorporationtoprepareaconsensusstatementthatprovides ; clinicalrecommendationsforachievingclearanceguidelinesforperitonealdialysis.Throughan ' analysisof806PDpatients,thegroupconcludedthatadequateclearancedeliveredwithPDcan  beachievedinalmostallpatientsiftheprescriptionisindividualizedaccordingtothepatient's  bodysurfacearea,amountofresidualrenalfunction,andperitonealmembranetransport  characteristics.Useof2.5Lto3.0Lfillvolumes,theadditionofanextraexchange,andgiving  automatedperitonealdialysispatientsa"wet"dayarealloptionstoconsiderwhenincreasing s weeklycreatinineclearanceandKT/V.RatherthanspecifyasingleclearanceorKT/Vtarget,the _ recommendedclinicalpracticeistoprovidethemostdialysisthatcanbedeliveredtothe K individualpatient,withintheconstraintsofsocialandclinicalcircumstances,qualityoflife,life 7  style,andcost.ThechallengetoPDpractitionersistomakeprescriptionmanagementanintegral #!s partofeverydaypatientmanagement.Thisincludesassessmentofperitonealmembrane "_ permeability,measurementofdialysisandresidualrenalclearance,andadjustmentofthedialysis "K prescriptionwhenindicated.  K ݌ #7 Ќ       Sy% &%v     KEYWORDS: Peritonealdialysis,adequacy,outcome. ݌ y%  Ќ  S*FG ddd Xdd Xdd X(#(#,+  1'& "!& " 1   S'_"& " S   Thewisegeneralinhisdeliberationsmustconsiderboth '_"" favorableandunfavorablefactors.Bytakingintoaccountthe 'K## favorablefactors,hemakeshisplanfeasible;bytakinginto (7$$ accounttheunfavorable,hemayresolvethedifficulties.  ݌ ?5)#%%  ?Ќ     S+b&*&     ԄӀSunTzu,TheArtofWar9 ݌-#!+b&&0   -Ќ     S,'Q,'     Thedailyregimenoffour2Lexchangeshaslongbeenthestandardized,acceptedcontinuous ,'& ambulatoryperitonealdialysis(CAPD)prescription.Overthelastfewyears,concern_has -(' surfacedregardingtherelationshipbetweentotalclearanceandclinicaloutcomesinperitoneal  dialysis(_PD_)patients,andseveralstudieshaveconfirmedthatacorrelationexists(1M3). J݌  Ќ       S.~+   TheCanadaMU.S.A.(_CANUSA_)(4)prospective,_multicenter_Ԁcohortstudyhasrecentlyprovided .~ specificdatathatconfirmthelinkagebetweensmallsoluteclearanceandpatientsurvival. j _CANUSA_Ԁresultshaveledustoreevaluateourbeliefsaboutclearance"targets,"whichat50  V L/wk/1.73mof_creatinine_Ԁclearance(_Ccr_)andweeklyKT/V>1.7mayhavebeentoolow. ݌  B Ќ     S 1     Asimilarrealizationbythehemodialysis(HD)community,in1989,resultedinanincreaseinthe   basichemodialysisprescriptionintheUnitedStates(5).Itisvitalthat_PD_Ԁpractitionersmakea p  similarconsciousefforttoincrease_PD_Ԁprescription.  !݌ \  Ќ     S>   "  Inlightofthe_CANUSA_Ԁfindings,theAdHocCommitteeonPeritonealDialysisAdequacymet >  inJanuary,1996.ThiscommitteeofinvitedexpertswasconvenedbyBaxterHealthcare *  Corporation,andtheobjectiveofthiscommitteewastoprovideaconsensusstatementthat   providesclinicalrecommendationsforachievingclearanceguidelinesforperitonealdialysis.It   shouldbeclearlystatedthattherecommendationsarebasedontheconsideredopinionofthe   committeeratherthanonanyvalidatedscientificdata.Theaimofthiscommitteewastoevaluate  clearanceguidelinesratherthanalloftheparameters,suchasnutrition,thatcomprise_PD_ v adequacy. "$#݌ b Ќ     SD &  TheabovementionedauthorsaremembersoftheAdHocCommitteeonPeritonealDialysis D Adequacy. &)'݌ 0 Ќ     Sro <(  Correspondenceto:P.Blake,DivisionofNephrology,LondonHealthScience_Centre_,Victoria r Campus,London,Ontario,CANADA,N6A4G5 <(l(݌ ^ Ќ     S@ )  Received25May1996;accepted12July1996. ))݌ @ Ќ  S#XXXAX#Snk SAXXXX BACKGROUND  n    S, <+  Whenonecomparestheclearancesachievedbythe"replacement"therapies(Figure1)itisclear , thatthesearenotreplacementtherapiesatall.Sincealldialysistechniquesare,atbest,poor   substitutesforthenaturalkidney,weneedtostrivetogiveasmuchdialysistotheindividual ! patientaspractical.Inthiscontext,interpretationofthe_CANUSA_Ԁresultsisparticularly " enlightening. <+l+݌ # Ќ     S%n $    -   FIGURE1  -.݌ %n         S&"a&!   .  Normalkidneyfunctionincomparisontorenalreplacementtherapy. ./݌ &" Ќ       SS   /  KNSC?x Xp@XE11#Q  /0݌ S Ќ       S* 01  Inthe_CANUSA_Ԁstudy,680newCAPDpatientswereenrolledinaprospectivestudyinten * CanadianandfourU.S.centerstodeterminetheeffectofclearancelevelsandnutritionon  morbidityandmortality.Thedialysisdosewasatthediscretionofthepatient'sindividual  investigatorandwasnotincreasedasresidualrenalfunction(_RRF_)declined.Infact,mean  peritonealKT/Vdidnotchangeoverthetwoyearsoffollowup,andperitoneal_creatinine_  clearanceincreasedonlyslightlyfrom44.2L/wk/1.73matbaselineto47.3L/wk/1.73mat24 v months(p<0.005,baselinevs24months). 01`1݌ b Ќ     SD ?5  The_CANUSA_Ԁstudydataconfirmthat"moreisbetter"inperitonealdialysis.Twoyearpredicted D patientsurvivaldatademonstratethatlowertotalsoluteclearancesareassociatedwithhigher 0  patientmortality(Table1).Actuarialtwoyearsurvivalwas78%.Ina_multivariate_Ԁanalysis,a5   L/week/1.73mincreaseintotal_creatinine_Ԁclearancewasassociatedwitha7%declinein   relativeriskofdeath,anda0.1UincreaseinweeklyKT/Vwasassociatedwitha6%declinein   relativeriskofdeath.Itshouldbenotedthatchangesintotal_creatinine_ԀclearanceandKT/Vin   the_CANUSA_Ԁstudyareprimarilyduetodecreasesinresidualrenalfunction,ratherthanto |  alterationsinperitonealclearance.Itiswidelypresumed,althoughunproven,thatthesefindings h! canbeextrapolatedtosupporttheexistenceofasimilarassociationforalterationsinperitoneal T" clearance. ?5o5݌ @# Ќ     S$" $ :  Sincethe_CANUSA_Ԁdataareusuallypresentedintabularform,thelargedifferenceinmortality $"  betweenthepredictedsurvivalforasustained_creatinine_Ԁclearanceof55and70L/wk/1.73m %! hasledsometoconsider70L/wk/1.73mtheminimum_creatinine_ԀtargetforCAPD.However, &! whenthesedataarepresentedgraphicallywithadditionalinterpolateddatapoints,thecurveis '" smoothanddoesnotplateau(Figure2).Whilethesedatasupporttheviewthatmoretotal (# clearanceisbetter,thesuggestedtargetlevelscanbequestionedforseveralreasons: :;݌ n)$ Ќ   L(03X ""  X<( ` hp x X<  S+P&*%  4?2  .3  Ԁ  Greaterlevelsoftotalclearanceareassociatedwithbettersurvival,thus,selectingonelevel +P& overanotherissomewhatarbitrary4??݌ +<' Ќ X XX   ?+ ` hp x X?""  X<( ` hp x X<  S~-(+-{( A2  .3  Ԁ  Theanalysisiscomplicatedbythefactthat_RRF_Ԁwasresponsibleforalmostallof_the ~-( variationoftotalclearance.A\B݌  Ќ X XX   ?+ ` hp x X?""  X<( ` hp x X<  SB? 2D2  .3  Ԁ  The_CANUSA_Ԁstudywasunabletodemonstrateacorrelationbetweensmallmolecule B clearanceandclinicaloutcomesindependentof_RRF_Ԁbecausetherewaslittlevariationin .~ peritonealclearanceinthestudypopulation2DD݌ j Ќ X XX   ?+ ` hp x X?""  X<( ` hp x X<  S Y  EG2  .3  Ԁ  Thedataareinferencesfromstatisticalmodeling(6)EGG݌   Ќ X XX   ?+ ` hp x X?""  X<( ` hp x X<  S>  ; PI2  .3  Ԁ  Thedataarebasedonuncontrolled,_nonrand_Ԅ_omized_ԀcrosssectionalcorrelationsPIJ݌ >  Ќ X XX   ?+ ` hp x X?" "  X<( ` hp x X<  S }  K2  .3  Ԁ  Correlationsbasedonclearancesthathavebeenmeasuredeverysixmonthsmay   significantlyoverstatethelevelsatwhichadverseeventsactuallyoccurduetowide   variancesintherateof_RRF_Ԁdecline(7)KL݌   Ќ X XX   ?+ ` hp x X?   S: 7    N   TABLE1  NN݌ :  Ќ       S }    O  _CANUSA_:PredictedTwoYearPatientSurvivalVersusSustainedCreatinineClearance OO݌   Ќ  S  *]QR ddFG(#(#], >,>>+  8MMM'_ _ $$8   S3 S   Q   Creatinineclearance   (L/week/1.73m)  QR݌ ?MMMM,!r  MMM ?Ќ     S3   %S   Predicted2yearsurvival  (%)  %SaS݌ UMMD,r  $$  MMMM $UЌ     S% qT  95 qTT݌ ?MMM,!%MM ?Ќ     S% EU  86 EUuU݌ UMMD,% $  MMM $UЌ     S85 /V  80 /V_V݌ ?MMM,!8MM ?Ќ     S85 W  82 W3W݌ UMMD,8 $  MMM $UЌ     SH W  70 WX݌ ?MMM,!MM ?Ќ     SH X  78 XX݌ UMMD, $  MMM $UЌ     SN Y  55 YY݌ ?MMM,!NMM ?Ќ     SN Z  72 ZZ݌ UMMD,N $  MMM $UЌ     Sa^ i[  40 i[[݌ ?MMM,!aMM ?Ќ     Sa^ =\  65 =\m\݌<20a $   MMM <Ќ     Sg   ]   FIGURE2  ]J]݌ g Ќ       SZ   ]  The_CANUSA_Ԁdatapresentedgraphically,withconfidenceintervalsthatarewideand  overlapping. ])^݌  Ќ   (#(##XXXAX*#m`d9)%`|0 X `V E X X  x m _          N-(&   SSAXXXX KEYPATIENTATTRIBUTESINFLUENCINGTHEDIALYSISPRESCRIPTION  S    Sqn a  Toachievethedesiredclearancelevels,individuallytailored_PD_Ԁprescriptionsareessential.Body q surfacearea(BSA),residualrenalfunction,andperitonealmembranetransportcharacteristicsare ] fundamentaltothe_PD_Ԁprescription.Inordertoconfirmthatitispossibletoachievethe I recommendedclearancelevelswithreasonable_PD_Ԁprescriptions,weexamineddatafrom806 5  randomlyselectedadultmaleandfemale_PD_Ԁpatientsfrom39U.S.centers.All806patients ! q underwentastandardfourhour2L2.5%dextroseperitonealequilibrationtest(PET). ab݌  ] Ќ     S L  e   BODYSURFACEAREA  ee݌   Ќ     S5 2  f  Bodysurfaceareaobviouslyaffectstheamountofdialysisapatientneeds.While1.73mis 5  consideredtheaverageadultBSA,inthese806patients(8)themedianbodysurfaceareawas !q  1.85m(Table2).Infact,75%ofthepatientsinthisstudyhadBSA>1.71m,reinforcingthe  ]  needtoindividualize_PD_Ԁprescriptionandutilizelargervolumesofsolution. ff݌ I  Ќ     S 8  Di   RESIDUALRENALFUNCTION  Diti݌   Ќ     S!q j  Residualrenalfunctionmakesiteasiertoachieveclearanceguidelines.Forexample,1_mL_/min !q  ofglomerularfiltrationrate(_GFR_),calculatedasthesumoftheureaand_creatinine_Ԁclearances  ] dividedby2(corrected_Ccr_),adds10L/wkof_Ccr_.Similarly,foreach1_mL_/minofurea I clearance,0.25isaddedtothetotalweeklyKT/Vfora70kgperson. jJj݌ 5 Ќ     Sw$t ,m  Theperitonealdialysisprescriptionmustbeadjustedas_RRF_Ԁdeclines.Itisrecommendedthat w onereplaceoverallsoluteclearancelossduetoadecreasein_RRF_Ԁwithasimilarincreasein c peritonealclearance._RRF_Ԁmustbemeasuredeverythreemonthsorpresumedtobeabsentin O determiningthe_PD_Ԁprescription.However,becausethedeclinein_RRF_Ԁisunpredictableandmay ; occuratdifferentratesfordifferentdiseasestates,specificcircumstances(e.g.,antibioticusage) 'w maymeritmorefrequentmonitoring. ,m\m݌ c Ќ     SR p   PERITONEALMEMBRANETRANSPORTCHARACTERISTICS  pq݌  Ќ     S; 8 q  Peritonealmembranetransporthasasignificantimpactondialysisclearanceand,therefore,the ;  _PD_Ԁprescription.Membranetransportcharacteristicsinthesamegroupof806patientswere '!w assessedusingthestandardPET(9).Adifferentdistributionofperitonealtransport "c characteristicsfromthatoriginallydescribedbyTwardowskiwasfoundinthisgroupofpatients "O (Figure3),possiblybecauseofthemuchhighernumberofpatientsinthecurrentstudy.Asmall #; fraction(5.6%)fellintothelowtransportgroup,whichisthehardesttotreatwith_PD_.Patients $'  withhighsolutetransportmembranescomprised10.4%ofthepopulation.NoteinTable3that %! peritonealtransportcharacteristicswererandomlydistributedwithineachBSAgroup. qq݌ &! Ќ     _SA(#'>#   !v    !vmv݌̌   =-($ TABLE2        SFC   (w  DistributionofBodySurfaceAream(n=806) (wdw݌ F Ќ  S  *pOP dd > >>QR(#(#p,@>,>,@>>+  8MMM' $$8   SL S   Ey   25th L percentile  Eyy݌ =MMM,!8 MMM =Ќ     SL   qz   Median  qzz݌ ?MMMM,!L MMM ?Ќ     SL   [{   75th L percentile  [{{݌ UMMD,8  $$  MMMM $UЌ     SK  H |  1.71 ||݌ =MM,!K MM =Ќ     SK  H ]}  1.85 ]}}݌ ?MMM,!K  MM ?Ќ     SK  H 3~  2.00 3~c~݌<20K   $   MMM <Ќ     S Q       FIGURE3  B݌  Q  Ќ       S D      PercentofpatientsineachPETgroup. !݌    Ќ   n n (#(##XXXAXSa#m`a9)%`|0] , `$V E , , n b m n n n n _ n n n n  n n n n  n n n n  n n n n  n n n n  n n n n  n n n n  n n n n  (#(#n n   _SLAXXXX SELECTINGAMEASUREOFCLEARANCE      S ]  /  TheweeklyCcrandKT/Vtargetsmaynotbeachievedsimultaneouslyintheindividualpatient  ] fortworeasons.Firstly,creatinineissecretedintotheglomerularfiltratebythekidney,while I ureaisreabsorbed.Clearly,theresidualrenalcreatinineclearance,evenwhenitisestimatedby 5 theaverageofrenalureaandcreatinineclearance,ishigherthantheresidualrenalureaclearance. ! Therelativecontributionofrenalcreatinineclearancetototal(renal+peritoneal)clearancetends   tobehigherthanthatofrenalureaclearancetototalKT/V. /_݌ ! Ќ     S;#"8 h  Secondly,becausethetransportofcreatinineacrosstheperitonealmembraneisslowerthanfor ;# urea,itishardertoachievehighperitonealcreatinineclearancethanitistoachieveperitoneal '$w KT/V.Thisisespeciallysoinautomatedperitonealdialysis(APD),whendwelltimesare %c  shorter.Thereisnodefinitiveproofregardingselectionofthemeasureofclearance.Untilthere %O!  aredatathatsupporttheuseofeitherCcrorKT/VexclusivelyasaclinicalmeasureofPD &;"! adequacy,bothshouldbeusedtoassesstherapyefficacy.Ifadiscrepancyexistsbetweenthese ''#" twomeasures,thatis,oneachievesKT/VbutnotCcr,thepatientshouldnotbeconsidereda ($# failure.Instead,thetargetsshouldbeconsideredinthetotalcontextofthepatient'smanagement )$$ throughcarefulreviewandongoingmonitoringofclinicalsymptoms. h݌ *%% Ќ     S-,}'+*'    CLINICALASSESSMENTANDQUALITYOFLIFECONSIDERATIONS  !݌ -,}'& Ќ     S-)p-(   Itisimportanttoevaluatethepatientfrequently,takingintoaccountclinicalassessment, -)' biochemicalparameters,andlifestyle,becauseachievingadequateclearancedoesnotguarantee  decreasedmortality.Clinicalassessmentshouldincludeevaluatingthepatient'suremic  symptoms,nutritionalstate,andcomorbiddisease.Ifapatientdoesnotmeettotalsolute  clearancetargets,butclinicalassessmentshowsthepatientisthriving,considerationoflifestyle t isimportantinthedecisionofwhetherornottomodifytheprescriptionortransferthepatientto ` hemodialysis.Frequentongoingassessmentisrequiredinthissituation.Conversely,ifapatient L  appearsuremicdespitemeetingclearancetargets,alterationsinprescriptionshouldbe 8  considered. 6݌ $ t Ќ     S c  o   RECOMMENDEDCLINICALPRACTICESTOACHIEVECLEARANCE   GUIDELINES  o݌    Ќ     S8 5    Therecommendedclinicalpracticeistoprovidethemostdialysisthatcanbedeliveredtothe 8  individualpatient,withintheconstraintsofsocialandclinicalcircumstances,qualityoflife,life $t  style,andcost. ݌ `  Ќ     S O  8  TherecommendednumericclearanceguidelinesforcontinuousPD(treatmentgiven24   hours/day)areshowninTable4.Theseguidelinesarefortotalclearance,peritoneal+renal. 8h݌  Ќ     S p   Onlywhenspecialclinicalorsocialcircumstancesdictateshouldthefirsttwolevelsof  p prescription("usecaution,""borderline")beacceptable.Exceptionstotheseguidelinesshouldbe  \ consideredwhenindividualpatientneedsandqualityoflifeconsiderationsexceedthegains H achievedfromincreasingcreatinineclearance.Forexample,a94yearoldpatientwithother 4 systemicdiseaseandCcr=50mL/wkwhoisasymptomaticmaychoosenottobeinvolvedwith   amoreaggressivetherapy. ֔݌   Ќ     SNK ߗ  Inrecommendingtheseguidelines,itmustalsobenotedthatanincreaseinperitonealclearance N willberequiredtocompensateforthedeclineinresidualfunction.InsituationswhereKT/V : guidelinesbutnotCcrtargetsaremet,attemptstoincreaseCcrshouldbemade,butfailuretodo &v soshouldnotbeconsideredanindicationfortransfertohemodialysis. ߗ݌ b Ќ     SQ -  Indiscussionsofdialysisadequacy,itisimportanttopointoutthatrenalandperitoneal  clearanceshavebeenconsideredequivalent.Onemilliliter/minuteofcorrectedCcr,or1Uof   KT/Vduetoresidualrenalfunction,isassumedtoequalthatfromperitonealclearance.These |! guidelinesassumethatanincreaseinperitonealclearancewillcompensateforthedeclinein h" residualfunction,althoughthishasnotbeenformallyproven.Mostopinionleaderswouldagree T# thatrenalclearanceismorevaluablethanperitonealclearance,butthisissueneedstoberesolved @$ byfurtherresearch. -]݌ ,%|  Ќ     S&"k&!      TABLE3  ڝ݌ &"  Ќ       ST(#(Q#   |  MedianValuesUsedtoModelEachBSA/PETGroup |݌ T(#! Ќ  S  *ST dd@>@>@>>@OP(#(#,>,>,>,>,>,>>+  8MMM')$")$ $$8   S *Z%)% S      J݌ =MMM,! *Z%# MMM =Ќ     S *Z%)%      ,݌ =MMM,! *Z%$ MMM =Ќ     S *Z%)%   ¢   Low  ¢݌ =MMM,! *Z%% MMM =Ќ     S *Z%)%      LA  ݌ =MMM,! *Z%& MMM =Ќ     S *Z%)%      HA  Ǥ݌ ?MMMM,! *Z%' MMM ?Ќ     S *Z%)%   q   High  q݌ YMMH, *Z%(  $$  MMMM $YЌ     Sm+&+j& s  >2.0m s݌ EMM4)m+&) MM EЌ     Sm+&+j& Y  BSA Y݌ =MM,!m+&*MM =Ќ     Sm+&+j& ,  2.08 ,\݌ =MM,!m+&+MM =Ќ     Sm+&+j&   2.13 0݌ =MM,!m+&,MM =Ќ     Sm+&+j& ԩ  2.15 ԩ݌ ?MMM,!m+&-MM ?Ќ     Sm+&+j&   2.11 ڪ݌ I?,m+&. $  MMM $IЌ     S, (},'    ʫ݌ (MM , (. (Ќ     S, (},' E  D/P Eu݌ =MM,!, (/MM =Ќ     S, (},'   0.49 H݌ =MM,!, (0MM =Ќ     S, (},'   0.59 ݌ =MM,!, (1MM =Ќ     S, (},'   0.76 ݌ ?MMM,!, (2MM ?Ќ     S, (},'   0.85 Ư݌ YMMH,, (3 $  MMM $YЌ  _   SS   1.71M2.0m а݌ EMM4)S MM E     SS   BSA ر݌ =MM,!SMM =Ќ     SS {  1.85 {݌ =MM,!SMM =Ќ     SS O  1.87 O݌ =MM,!SMM =Ќ     SS #  1.86 #S݌ ?MMM,!SMM ?Ќ     SS   1.84 )݌ I?,S $  MMM $IЌ     Sfc ٵ   ٵ݌ (MM f (Ќ     Sfc   D/P Ķ݌ =MM,!fMM =Ќ     Sfc g  0.43 g݌ =MM,!fMM =Ќ     Sfc ;  0.59 ;k݌ =MM,!f MM =Ќ     Sfc   0.71 ?݌ ?MMM,!f MM ?Ќ     Sfc   0.86 ݌ YMMH,f  $  MMM $YЌ     Sv պ  <1.71m պ݌ EMM4) &MM EЌ     Sv   BSA ݌ =MM,! MM =Ќ     Sv   1.60 ݌ =MM,!MM =Ќ     Sv c  1.56 c݌ =MM,!MM =Ќ     Sv 7  1.59 7g݌ ?MMM,!MM ?Ќ     Sv    1.65  =݌ I?, $  MMM $IЌ     S, |)    -݌ (MM , | (Ќ     S, |)   D/P ݌ =MM,!, |MM =Ќ     S, |) {  0.42 {݌ =MM,!, |MM =Ќ     S, |) O  0.59 O݌ =MM,!, |MM =Ќ     S, |) #  0.71 #S݌ ?MMM,!, |MM ?Ќ     S, |)   0.84 )݌<20, | $   MMM <Ќ     S 2      A XAX#  Aд#A  BSA=bodysurfacearea;PET=peritonealequilibrationtest;  2 LA=lowaveragetransportmembrane;HA=highaveragetransportmembrane;   D/P=dialysatetoplasma_creatinine_Ԁconcentrationratio.#AXX A7##XXXAXy#AXXXXԀ ݌ j  Ќ       S L       TABLE4  ݌  L  Ќ       S ?      RecommendedClearanceGuidelines ݌   Ќ  S  *UV dd>>>>>>>ST(#(#, >,>,>>+  8MMM'! !  $$8   SH E  S      Creatinineclearance H  (L/week/1.73m)  %݌ =MMM,!4  MMM =Ќ     SH E    ,   KT/V H  (weekly)  ,h݌ ?MMMM,!4  MMM ?Ќ     SH E    B   Guidelines  B~݌ UMMD,H   $$  MMMM $UЌ     SD F  <49 Fv݌ =MM,!!MM =Ќ     SD   <1.70 I݌ ?MMM,!"MM ?Ќ     SD   Usecaution  ݌ UMMD,# $  MMM $UЌ     SJ   50M59 ݌ =MM,!J$MM =Ќ     SJ   1.70M1.89 ݌ ?MMM,!J%MM ?Ќ     SJ   Borderline ݌ UMMD,J& $  MMM $UЌ     S] Z   60M69 ݌ =MM,!]'MM =Ќ     S] Z   1.90M2.09 ݌ ?MMM,!](MM ?Ќ     S] Z   Acceptable ݌ UMMD,]) $  MMM $UЌ     Sm w  >70 w݌ =MM,!*MM =Ќ     Sm J  >2.09 Jz݌ ?MMM,!+MM ?Ќ     Sm !  Desirable !Q݌<20, $   MMM <Ќ        ?Wxhd$~bp@+pddx bEb V9tf S_#XXXAX:# ݌̌  __SNK SAXXXX ACHIEVINGTHECLEARANCEGUIDELINES  N.    S i &  Forsomepatients,achievingtherecommendedclearanceguidelinesmayrequireasubstantial  / increaseinthedialysisprescription.Thisraisestheconcernthattargetsmayonlybeachievedby 0 anunacceptableincreaseinthecostofPDand/oradeteriorationinthepatient'squalityoflife. 1 Thebenefitsofincreasingclearancemustbebalancedwiththerisksforsomepatientsassociated 2 withlargerfillvolumes.Theincreaseinintraabdominalpressureassociatedwithhigherfill l 3 volumesmaycontributetoherniasforthosepatientspronetothemandmayalsoresultin X!4 increasedperitonealfluidabsorptionandlessnetultrafiltration.Increasedglucoseabsorption D"5 associatedwithlargerfillvolumesisespeciallyaconsiderationforpatientswithhightransport 0#6 membranes. &V݌ $l7 Ќ     S% [%    Toevaluatetheoptionsforachievingclearances,wecreated12standard"patients"bytakingthe % 8 medianvaluefromeachofthe12possibleBSA/PETcombinations(Table3).These12patients &!9 werethenmodeledusingacomputerprescriptionprogram(PDADEQUEST)),Baxter '": Healthcare,Deerfield,IL)toassesswhichprescriptionsmeettherecommendedguidelinesand r(#; thusprovideatemplateforaninitialPDprescriptionforapatientofknownBSAandperitoneal ^)$< transportcharacteristics.Theprogram,PDADEQUEST)),hasbeenscientificallyvalidatedin J*%= asmallwellcontrolledstudy(10,11).IthasalsobeenclinicallyvalidatedforCAPDpatientsina 6+&> largemulticenterstudy[seeVoneshetal.(12)].WhilevalidationstudiesforAPDpatientsare ",r'? underway,resultsarenotyetavailable.However,clinicalvalidationofakineticmodel_very -^(@ similarto_PD_ԀADEQUEST))wascarriedoutforbothCAPD(n=75)andAPD(n=25)  patientsbyRobertsonetal.(13).TheirresultsaresimilartotheresultsreportedbyVoneshand  _Rippe_Ԁ(11),withpredictedclearancesagreeingwithclinicaldatatowithinanaveragedifference  of10%.Althoughthemodelingwasdonewith_PD_ԀADEQUEST)),thereareothermodels t available,includingseveralcommercialprograms. ݌ ` Ќ     S B    Themainpointofthisexercisewastodemonstratethatalmostallpatientswhodevelopanuria  B whilebeingtreatedby_PD_Ԁcanachieveacceptabletargetsbyidentifyingmembrane  . characteristics,measuringclearance,andmodifyingthedialysisprescriptionwhennecessary.The   predictedclearancespresentedheredonotrepresentabsolutevaluesbutapproximatelevelsof   clearancefor"typical"patients.Forthemajorityofpatients,severalprescriptionswerepossible    thatmetacceptableclearance,lifestyle,andcostcriteria.Itisworthnotingthatevenpatients   withlowtransportmembranes(whocomprisedonly5.6%ofthesamplestudied),canbe z  managedreasonablywellwith_PD_Ԁiftheyaresmallorhavesufficientresidualrenalfunction. #݌ f  Ќ     SH   c   THEIMPACTOFDIALYSISPRESCRIPTIONONCLEARANCE  c݌ H  Ќ     S; R  WemodeledselectedprescriptionsforeachBSAgrouptoillustratetherelationshipbetween  therapylevelsandclearance.InFigures4through13(4ih   5  /  46XhlM   7M,4jMlh   5  /  56UhiM   7M,4kM4h   5  /  66RhfM   7M,4lMh   5  /  76OhcM   7M`,4mMh   5  /  86Lh`M   7M(,4nMh   5  /  96Ih]M   7M,4oMTh   5  /  106FhZM   7M,4pMh   5  /  116DhXM   7MH,4qMh   5  /  126BhVM   7Mt,4rMh   5  /  136@hTM   7M),themodeled z _creatinine_ԀclearancesandKT/Vareshownwithminimumtargetclearancesdepicted.The j patientsareassumedtohavenoresidualrenalfunction##the"worstcase"scenario.Ineachfigure, V threeregimesareshown:standardfourexchangeCAPD;threetypicaldaytimeexchangesand B twoexchangesduringthenight(oneusinganautomatedexchangedevice),labelednight .~ exchangedevice;andAPD.Thefollowingassumptionsweremadeduringmodeling: R݌ j Ќ  / /""  X<( ` hp x X<  SY '2  .3  Ԁ  CAPD:fourexchangesperdayandanaverage_ultrafiltration_Ԁ(_UF_)volumeof1.5L'݌  Ќ X XX   ?+ ` hp x X?""  X<( ` hp x X<  S>; 2  .3  Ԁ  Nightexchangedevice:threetypicaldaytimeexchangesandtwofivehourexchanges > overnight(oneusinganautomatednightexchangedevice),andaverage_ultrafiltration_ *z volumeof1.5LE݌ f Ќ X XX   ?+ ` hp x X?""  X<( ` hp x X<  SU s2  .3  Ԁ  APD:overnighttreatmentoftenhourswithdaytimedwell("wetday":adaytimedwell  infusedasthelaststepoftheAPDtreatment)andanaverage_ultrafiltration_Ԁvolumeof1.5   Ls+݌ ! Ќ X XX   ?+ ` hp x X?""  X<( ` hp x X<  S#b" C2  .3  Ԁ  Allpatientsweremodeledwithan_ultrafiltration_Ԁofbetween1and2L/day.Forthehigher #b transportpatients,the_UF_Ԁwascloserto1than1.5._UF_ԀwasnotuniversallyheldconstantC݌ #N Ќ X XX   ?+ ` hp x X?   S% =%  A  ThisseriesoffiguresdemonstratesthatyoucanachievetargetsforpatientswithdifferingBSA %  andperitonealmembranecharacteristicsbyindividualizingpatientprescription.Figures4 |&! through7(4sM&h   5  /  46hM   7M,4tMh   5  /  56hM   7MR ,4uM h   5  /  66hM   7M ,4vM~ h   5  /  76 h M   7M )showthebenefitofreplacingroutine2Lfillvolumeswith2.5Linthe h'"  prescriptionsofpatientswithBSAlowerthanthe25thpercentile.Significantly,largerfill X(#! volumesallowalmostallpatientstoreachclearanceandKT/Vtargets,evenwhentheybecome D)$" anuric.Themainexceptionisthegroupofpatientswithlowtransportmembranes.Itshouldbe 0*%# notedthatthese"small"patientshadamedianBSAof1.6m.Asimilarbenefitisseenwhen3 +l&$ Lfillvolumesareusedratherthan2.5LinthepatientswithBSAbetweenthe25thand75th ,X'% percentile(Figures8M11:4wM h   5  /  86 h M   7M ,4xM h   5  /  96}hM   7MH,4yMh   5  /  106zhM   7Mt,4zMh   5  /  116xhM   7M).Eveninthelargeanuricpatient,a3Lfillvolume ,D(& providesadequatedialysisinmostindividuals(Figures12,13:4{Mph   5  /  126h#M   7M8T,4|Mh   5  /  136 h!M   7MdR).Thesamebenefit_should -4)' benotedforthelarge(>75thpercentile)patientshownin4}Mh   5  /  Figure126hM   7M. Aq݌  Ќ     SFC   Attheendof24months,the_CANUSA_Ԁpatientshadamean14L/wk/1.73mof_creatinine_ F clearancefromresidualrenalfunction(4~Mh   5  /  Figure146h-M   7M,^).Ifthislevelofresidualrenalfunctionis 2 addedtothe_creatinine_ԀclearanceshowninFigure9forthemiddlesizedpatient,thebenefitof "r residualrenalfunctioncanbeclearlyillustrated(4Mh   5  /  Figure15.68hLM   7MX}) ݌  ^ Ќ     S Q    ?xhd$~bp@+pddx bE@ b V9 f ݌̌  S#XXXAX#S6  3 SAXXXX%     FIGURE4  6       S Q      CreatinineclearancelevelsforpatientswithBSA<1.71m,   noresidualrenalfunction,and2Lfillvolumes. ݌   Ќ       S"r     .  %JKVFBx \R pL@XE"R R r  .z݌ "r  Ќ       Sro     %   FIGURE5  ݌ r  Ќ       SX      CreatinineclearancelevelsforpatientswithBSA<1.71m, X  noresidualrenalfunction,and2.5Lfillvolumes. D  KVFBx \( pm@XE( ( H    ݌ 0  Ќ       S>*%);%   "  % ""݌̌   , (      SS   w#  %   FIGURE6  w##݌ S Ќ       SF   c$  KT/VlevelsforpatientswithBSA<1.71m,  noresidualrenalfunction,and2Lfillvolumes. c$$݌  Ќ       S g   %  %#KVFBx \( p]@XE ( (  H  %&݌  g Ќ       S5   ;'  %   FIGURE7  ;'w'݌ 5 Ќ       S{(x   '(  KT/VlevelsforpatientswithBSA<1.71m, { noresidualrenalfunction,and2.5Lfillvolumes. '(c(݌ g Ќ       SI   )  _%'KV FBx \2D p]@XE2D 2D Rd  ))݌ I Ќ   I-(      SS   -+  %   FIGURE8  -+i+݌ S Ќ       SF   ,  CreatinineclearancelevelsforpatientswithBSAbetween1.71and2.0m,  noresidualrenalfunction,and2.5Lfillvolumes. ,U,݌  Ќ       S g   -  %+KV FBx \ p@XE    > __ --݌  g Ќ       S^   1/  %   FIGURE9  1/m/݌  Ќ  CreatinineclearancelevelsforpatientswithBSAbetween1.71and2.0m,