慢性肾脏病患者疾病管理课件

1.1.MANAGEMENTOFTHEPATIENTWITHCHRONICKIDNEYDISEASEMedicineHousestaffConference2/13/2009

MargaretAKiserMDPhD,

2.MANAGEMENTOFTHEPATIENTWITHOutlineChronicKidneyDiseaseDefinitionsEpidemiologyScreeningforCKDTreatingComplicationsofAdvancedCKDHypertensionControlofvolumeAlterationsinbonemetabolismAnemiaNutritionHyperkalemiaSuggestedK-DOQIactionplanbasedondiseaseseverityWhentoreferandwhySlowingProgressionofCKDEvidencesupportingantihypertensiveuseCardiovascularRiskModificationGettingthewordout3.Outline3.WhatisChronicKidneyDisease?4.WhatisChronicKidneyDiseaseDefiningCKDKidneydamagefor

3monthsasdefinedbystructuralorfunctionalabnormalitiesofthekidney,withorwithoutdecreasedGFR,manifestbyeither:Pathologicalabnormalities;orMarkersofkidneydamage,includingabnormalitiesinthecompositionofthebloodorurine,orabnormalitiesinimagingtestingGlomerularFiltrationRate(GFR)<60ml/min/1.73m2for

3months,withorwithoutstructuralkidneydamage5.DefiningCKDKidneydamageforEstimatesofU.S.ChronicKidneyDiseasePopulationin200019,000,000ChronicKidneyDisease372,000Dialysis80,000Transplant6.EstimatesofU.S.ChronicKidnStagesofCKDProposedNKF-K/DOQIGuidelines.NKFClinicalNephrologyMeetings2001;Orlando,Fla.50403020<15GFR(mL/min/1.73m2)

1KidneyDamage

2MildGFR

3ModerateGFR

4SevereGFR

607080905Kidney

FailureCKDContinuum“CKD”ESRD

6RRT7.StagesofCKDProposedNKF-K/DOPrevalenceofCKD1 Kidneydamage >90** 10,259 5.82 MildGFR 60–89** 5,300–7,100 3–43 ModerateGFR 30–59*** 7,553 3.34 SevereGFR 15–29 363 0.25 Kidneyfailure <15ordialysis 300 0.1

12.4–13.4 GFR PrevalenceinUSPop.*

Stage Description (mL/min/1.73m2) N(1,000s) %*Populationof177millionadultsageover20**withpresenceofproteinuriaorhematuria+/-structuralchanges***donotneedproteinuriaorhematuria,justGFR<608.PrevalenceofCKD1 KidneydamaAGEANDRACECaucasianHispanicNativeAmericanAfricanAmerican1151/million2243/million2669/million4863/millionFurther,AfricanAmericansdevelopESRDatayoungerage55.8vs62.2yoAlthoughonly12.6%oftheUSpopulation,AfricanAmericansconstitute50%oftheESRDpopulationPointprevalenceofESRDUSRDS2007AnnualReportAJKD51,Suppl1,Jan20089.AGEANDRACECaucasianHispanicNFamilialInfluencesInheritedNephropathiesFamilyhistoryisastrongriskfactorfordiabeticnephropathyInallethnicgroupsstudiedtodatediabeticsiblingsofptswithESRD2/2DMwereatmarkedlyincreasedriskofdevelopingESRD.ParticularlycommoninAfricanAmericanswithanincreasedincidencerateof4-25foldgreaterthanCaucasiansAJKD2008,51(1),29-3710.FamilialInfluencesInheritedNEtiologyofChronicKidneyDiseaseUSRDS200111.EtiologyofChronicKidneyDisIdentifyingpatientsatrisk:

NationalKidneyFoundationRecommendations(KDOQI)IndividualsatincreasedriskforCKDshouldbetestedatthetimeofhealthevaluationstodetermineiftheyhaveCKD.Thisshouldincludepatientswith:-DMHTNAutoimmunediseasesChronicsystemicinfectionsRecoveryfromacuterenalfailureAge>60yrsFamilyhistoryofkidneydiseaseExposuretodrugsorproceduresassociatedwithanacutedeclineinkidneyfunctionKidneydonorsandtransplantrecipients

(AJKD,39,2002,pS214)12.Identifyingpatientsatrisk:

RelationshipofSerumCreatininetoGFR13.RelationshipofSerumCreatiniEstimationofGFRGFRcanbeassessedbytherenalclearanceofasubstance

ClearanceofsubstanceX(Cx)=UxVx/Sx

RecallGFR*Sx=UxVx

(amountfiltered=amountexcreted)Cx=UxV/Sx

Cx=GFRTwoimportantassumptions:MarkerneithersecretedorabsorbedSteadystateExamplesofmarkers:inulin,iothalamate,iohexol,serumcreatinine,cystatin-C14.EstimationofGFRGFRcanbeasCalculationofGFRMethodsofcalculationCockcroft-GaultformulaMDRDformula/modifiedMDRD15.CalculationofGFR15.TheCockcroft-Gaultcalculation

GFRml/min/1.73m2=(140-age)xLeanBWKg72xScreatininemg%

(x0.85forFemales)16.16.MDRDGFRFormula*170x[SCr]-0.999

x[Age]-0.176

x[0.762iffemale]x[1.180ifblack]x[Alb]+0.318ModifiedMDRDFormula186.338x[SCr]-1.154x[Age]-0.203x[1.212ifblack]x[0.742iffemale]MDRDGFR*FromLeveyetal,1999AnnInternMed130:461-470(Acalculatormaybefoundat)17.MDRDGFRFormula*MDRDGFR*From84F22M66M66FWt(kg)45.5104.577.271.8Screat1.21.21.21.2eGFR26.9142.766.152.3(CalculatedwithCockcroft-Gault)18.84FUrineProtein/CreatinineRatioBasedontheassumptionthatinthepresenceofstableGFR,urinecreatinineandproteinexcretionconstantGinsbergetalfirstdemonstratedastrongcorrelationbetweensingleUrineP/Cand24hurinein46ambulatorypatientsatasinglecenter,r=0.97ImportantcaveatsLeanbodymassTimingofurinecollectionRelationshipofspotand24urineproteinGroupA:Lowcreatinineexcretion,slope=1.11GroupB:IntermediateCrexcretion,slope=0.97GroupC:HighCrexcretion,slope=0.7719.UrineProtein/CreatinineRatFig1Correlationbetweenlnspotmorningurineprotein:creatinineratioandlog24hoururinaryproteinin177non-diabeticpatientswithchronicnephropathiesandpersistentclinicalproteinuria20.Fig1CorrelationbetweenlnsPhysiologicChangesinChronic

KidneyDiseaseIncreasedsinglenephronGFRAfferentarteriolarvasodilationIntraglomerularhypertensionLossofglomerularpermselectivityInabiltytoappropriatelydiluteorconcentratetheurineinthefaceofvolumechallenge21.PhysiologicChangesinChronicAnatomicandHistologicFeaturesDueto

GlomerularHypertensionGlomerularhypertrophyFocalsegmentalglomerulosclerosiswithhyalinosisInterstitialfibrosisVascularsclerosisEpithelialfootprocessfusion22.AnatomicandHistologicFeaturPathogenesisofSecondaryGlomerulosclerosisNephronMassGlomerularVolumeandGlomerularHypertensionEpithelialCellDensityandFootProcessFusionGlomerularSclerosisandHyalinosisPrimaryInsultProteinuria23.PathogenesisofSecondaryGlomHypertensioninCKD24.HypertensioninCKD24.RecommendationsforAnti-hypertensivesinPatientswithChronicKidneyDiseaseTreatmentisindicatedatanystageofthediseaseUsedrugsthatlowerglomerularcapillarypressure(ACEinhibitors,ARB,verapamilanddiltiazem)Goalistokeepthebloodpressure<130/80mmHg(<120SBPinDM)25.RecommendationsforAnti-hyperEffectsofVariousAnti-hypertensivesonGlomerularCapillaryPressureAfferentArterioleEfferentArterioleDihydropyridinesNifedipineFelodipineAmlodipineVasodilatePressureARBVerapamilDiltiazemVasodilatePressureVasoconstrictACE-I26.EffectsofVariousAnti-hypertNumberofMedicationstoAchieveGoalBPin5TrialsofDM/RenalDisease

Bakris.JClinHypertens1999;1:141.27.NumberofMedicationstoAchieAHierarchyofAgentsACE-IARB

-BlockersThiazideDiureticsVasodilators-BlockersCentralAgentsCCB’sMorePreferredLessPreferred28.AHierarchyofAgentsACE-I-BlVolumeManagement-Diuretics

%FilteredNa+SiteofAction Diuretic ExcretedNa+-K+-2Cl-carrier Furosemide inLoopofHenle Bumetanide 20% Torsemide EthacrynicacidNa+-Cl-carrier Thiazides 3-5%inthedistaltubule MetolazoneNa+channelinthe Amiloride 1-2%corticalcollecting Triamtereneduct Spironolactone(indirect)29.VolumeManagement-Diuretics NatriureticResponsetoFurosemideatDifferentLevelsofRenalFunctionGFR150ml/minGFR15ml/min1250mEq125mEq250mEq25mEq30.NatriureticResponsetoFuroseDiureticToleranceTypeI:Short-termDecreaseintheresponsetoadiureticafterthefirstdoseTeleologically--appropriateresponsetovolumedepletionTypeII:Long-termHypertrophyofdistalnephronsegmentsallowinggreatersodiumresorption31.DiureticToleranceTypeI:ShorAlgorithmforDiureticUseRenalInsufficiencyCrCl<50LoopDiureticDetermineEffectiveDose:5-10XUsualDoseAdministerasFrequentlyasNecessaryThiazideAccordingtoCrCl<20ml/min20-50>50ml/min50-100mg/50-100mg/25-50mg/daydaydayADDAddDistalDiureticDrugFromBraterDGNEngJMed1998;339:38732.AlgorithmforDiureticUseRenaAlterationsinBoneandMineralMetabolism33.AlterationsinBoneandMineraPTHPiCa2+RenalMass25(OH)D31,25(OH)2D31-alpha-hydroxylase1-alpha-hydroxylase+Acidosis+HyperparathyroidRelatedBoneDiseaseImpairedAbsorptionOsteitisFibrosaCystica34.PTHPiCa2+RenalMass25(OH)D31ReducedRenalMassGFR<65<40<25

IncreasedPTHSecretionDecreased1,25-DHyperphosphatemiaHypocalcemia35.ReducedRenalMassGFR<65<4CalciumandPhosphorusBalance:

NationalKidneyFoundationRecommendations(KDOQI)Inaddition,ithasbecomeclearthatCKDpatientshaveanutritionaldeficiencyof25-OHVitaminDwhichitselfleadstoanincreaseinPTHsecretionLevelsof25-OHDshouldbemeasuredwhenPTH-Intact>70pg/mlandsupplementationinstitutedifnecessary,alevelof<30ng/mlisabnormaland<15ng/ml,moderatetosevereTreatment<5ng/ml50,000UErgocalciferol/wkx12,thenqmox65-15ng/ml50,000/wkx4,thenqmox616-30ng/ml50,000/monthx6Measure25(OH)-Dat6monthsMaintenance800-1200IUqd

(AJKD,39,2002,pS214)36.CalciumandPhosphorusBalanceCalciumandPhosphorusBalance

KDOQIRecommendationsStage3CKD,GFR30-59MeasureCa,PhosandPTH-Ievery12monthsTargetlevelsCalciumWNLforlabPhos>2.7-4.6mg/dLCaXPhos<55PTH-I30-70pg/mlStage4CKD,GFR15-29MeasureCa,PhosandPTH-Ievery3monthsTargetlevelsCapreferablyWNLforlabPhos>2.7-</=4.6mg/dLCaXPhos<55PTH-I70-110pg/ml37.CalciumandPhosphorusBalanceCalciumandPhosphorusBalance

KDOQIRecommendationsHowarethesegoalsachieved?Controlofdietaryphosphorusintaketo0.8-1g/dMayneedinitiationof“Phosphatebinders”withmealsWhen25(OH)-D>30pg/mlandPTH-I>target,initiatetreatmentwithexogenous“ActiveVitaminD”AfewpatientswithveryelevatedPTH-IvaluesmaybenefitfromCalcimimetics(AJKD,39,2002,pS214)38.CalciumandPhosphorusBalanceCalciumandPhosphorusBalance:

LimitPhosphorusintaketo0.8-1.0g/dHighPhosphorusFoodsDairyproducts(Cheese,icecream,milk),nuts,peanutbutter,biscuits,processedmeats-hotdogs,chocolate,darksodas(Coke,Pepsi),beansLowerPhosphorusChoicesCreamcheese,sourcream,Gingerale/sprite,sherbet,non-dairycreamer39.CalciumandPhosphorusBalanceUseofPhosphatebindersGivenwithmeals,timingessentialAluminumbasedmedicines;(Basaljel,Amphogel)CalciumBasedCalciumCarbonate/MagnesiumCarbonate(Magnebind)CalciumCarbonate(Tums,Calcichew,Calcimix)CalciumAcetate(Phoslo)40.UseofPhosphatebinders40.UseofPhosphatebindersTheuseofcalciumbasedbindersisnowfallingoutoffavorbecauseoftherecognitionofacceleratedvascularcalcificationproposedtobeassociatedwiththem(Disputedbythemanufacturersofsame)Sevelamerhydrochloride(“Renagel”),cationicpolymer,bindsphosphatethru’ionexchange,canpromote/worsenmetabolicacidosisNewproductSevelamercarbonate(“Renvela”)doesnotleadtoacidosisLanthanumcarbonate(“Fosrenol”),longtermeffectsunknownVERYEXPENSIVE(Sevelamer800mgtab$1.93each,dosevaries3-9tabsaday,$173-521eachmonth,Fosrenol1000mgtab$4.87each,dose3tabsdaily,$438eachmonth)41.UseofPhosphatebindersTheusVitaminDSterolsSeveralVitaminDsterolsarenowavailabletoreplacenaturallyoccurring1,25Vitamin-D3,levelsofwhichfallwithdecliningrenalmassRocaltrol(Calcitriol,oral)Doxercalciferol(Hectoral,D2prohormone,availableinoralandparenteralforms)Paracalcitol(Zemplar),oralandparenteralformsavailable42.VitaminDSterols42.KDOQIRecommendationsforuseofVitaminDsterolsIncompliantpatientswithstablerenalfunction,Initiate“ActiveVitaminD”(1,25-OHD3)supplementswhen:25-(OH)D>30pg/ml,PTH-I>target,Ca<9.5,Phos>4.6Calcitriol0.25-1.0mcgpoqd(Rocaltrol)Doxercalciferol2.5-10mcgpotiw(Hectoral)Paracalcitol1-4mcgpoqd(Zemplar)CheckCaandPhosqmonthx3monthsthenq3monthsandcheckPTH-Iq3monthsMonitorcloselybecauseofthesignificantriskofdevelopinghypercalcemia(AJKD,39,2002,pS214)43.KDOQIRecommendationsforuseTheCalcimemeticsCalciumSensingReceptor(CaR)Cinacalcet(SensitizesCaRtoCa2+)NucleusVDRVitaminD

SerumCalciumPTHInhibitoryStimulatoryCellularProliferationTheparathyroidcell44.TheCalcimemeticsCalciumCinacaTreatmentofSecondaryHyperparathyroidismCalcimimeticagentsRapidonset(hours)InhibitPTHsecretionInhibitPTHsynthesisInhibitparathyroidcellularproliferationDecreaseserumcalciumVitaminDSterolsActongenomicreceptorSlowonset(daystoweeks)InhibitPTHsynthesisIncreaseserumcalcium45.TreatmentofSecondaryHyperpaPhosphorusCa2+1,25(OH)2D3(UseCautiously)NewParadigminTreatmentofSecondaryHyperparathyroidismNon-calciumBasedBindersCinacalcetPTH46.PhosphorusCa2+1,25(OH)2D3NewPComplicationsofLongTermCalciumandPhosphorusimbalanceTertiaryhyperparathyroidismRenalosteodystrophyDemineralizationBonepain FracturesSystemictoxicityCutaneous-CalciphylaxisCardiovascular,acceleratedvascularcalcificationNervous47.ComplicationsofLongTermCal48.48.49.49.ParathyroidectomyIndicationBio-IntactPTH>800pg/mLrefractorytomedicaltherapySeverehypercalcemiaProgressivehighturnoverbonediseaseComplicationsMayresultinexcessivelowPTHlevelsSymptomatichypocalcemiaRiskforinjurytorecurrentlaryngealnerve50.ParathyroidectomyIndication50.AnemiaofChronicKidneyDiseaseDevelopswhentheGFRdecreasesto<30-35ml/mindecreasingproductionoferythropoietin2/2reducedrenalmassUremicinhibitionofbonemarrowDecreasedRBClife-spanPTHinducedmarrowfibrosisIrondeficiencyAluminumrelatedbonediseaseNormochromic,normocytic51.AnemiaofChronicKidneyDiseaWhyTreatAnemia?Levinetal.AmJKidneyDis.1996;27:347-354.P=0.0062=1g/dLdecreaseinHgb6%increaseinriskofLVH175-PatientCKDStudy52.WhyTreatAnemia?Levinetal.Anemia-TreatmentGuidelinesGoalHgb11-12RecombinanterythropoeitinEpogen/Procrit50-150U/kg/wkSQDarbopoetinalfa(ARANESP)Start0.45mcg/kgSQonceevery2weeks,usuallydosedeverythreetofourweekswhenpatientisstableinthetherapeuticrangeRecentconcernsreincreasedriskofcardiovasculareventsassociatedwithanelevatedHgbinassociationwithuseofhighdosesoftheseproductsIronGoalFerritin>200,TSAT>20%OralagentsChromagen:33%ironFerroussulfate:20%ironNiferex(PolysaccharidewithVitC):150mgelementalironFerrousfumurate:33%ironFerrousgluconate(Fergon):12%ironOralagentsdonotworkwell,primarilyb/oilltoleratedGIsideeffects53.Anemia-TreatmentGuidelines53.Nutrition

Balancingtheimpactofdecreasedproteinintakeontherateofprogressionofrenaldisease,againsthypoalbuminemiaandmalnutritionCanwerestrictproteinintakesufficiently,withoutleadingtomalnutrition,especiallyimportantinpatientswitheGFR<25ml/min54.Nutrition54.SerumAlbuminattheStartof

DialysisintheU.S.ESRDPopulationObradoretal.JAmSocNephrol1999;10;p.1795Mean3.2+/-0.7Median3.355.SerumAlbuminatthe

SerumAlbuminConcentration(gm/dl)

OddsRatioofDeath

Lowrie,SeminarsinDialysis.Vol10,No2(Mar-Apr)1997,p.1161994Data<2.52.5-3.03.0-3.53.5-4.04.0-4.5>4.50.50.71.01.52.02.53.04.05.06.08.010.012.014.0Albumin(gm/dl)OddsRatioofDeathAlbuminunadj.CaseMixadj.CaseMix+Labadj.ReferencearenotdifferentfromBarswithoutsymbols=p<.05=p<.01Reference056.

SerumAlbuminConcHyperkalemiaAcommonreasonforinitiationofRRTThekidneyistheonlyrouteforexcretionofdietaryintake,thusthereislimitedexcretionasGFRfalls,potentiallyleadingtoincreasedserumlevelsManypatientswithCKDalsohaveatendencytoretainpotassiumbecauseofstimulationoftheRenin/Angio/AldosystemDiabeticsmayhaveatypeIVRTA(hyporeninemichyperaldosteronism)UseofACE-Icanexacerbatehyperkalemia57.HyperkalemiaAcommonreasonfoHyperkalemiaTreatmentRestrictionofintakeDiureticsKayexelate,longtermusecanleadtocolonicmucosaldefects58.Hyperkalemia58.HyperkalemiaHighPotassiumfoodsFruitsVegetablesOtherfoodsApricotArtichokeBran/branproductsAvocadoAsparagusCoffee,TeaBananaBeansChocolateCantaloupe,HoneydewBrusselsproutsCoconut,GranolaDates,Figs,driedfruitsLentils,legumesMolassesMango,PapayaLimas,Peas,OkraMilk,IcecreamOrange,NectarineParsnips,RutabagaNuts/seedsPeaches,PrunesPotatoesSnuff/chewingtobaccoRaisins,PersimmonsTomatoesSaltsubs/LitesaltJuicesoftheseWintersquashfruitsSaltfreeveg.juice59.HyperkalemiaHighPotassiumfooHyperkalemiaLowPotassiumfoodsFruitsVegetablesStarchesApples/applesauceBroccoliRiceBlackberriesBeans,green/waxNoodlesBlueberries/CranberriesBeets/carrots/cornBread/breadproductsCherries/grapes/gooseberriesCabbage/cauliflowerCerealsFruitcocktailCucumber,lettuceCakes,cookiesPears,canned/pineappleEggplant/onionsPies(notchocolateorPlums/raspberries/StrawberriesSummersquashhighKfruit)Mandarinoranges/TangerinesMushrooms,rawRhubarb,WatermelonParsley,radish,turnipJuicesofthesefruitsGreens(collards,kaleturnip,mustard)Peas,green60.HyperkalemiaLowPotassiumfoodCardiovascularRiskIndividualswithCKDareatincreasedriskforCVD,theyshouldbeconsideredinthe“highestriskgroupforevaluationandmanagement”accordingtoNKFrecommendations.Remember,thereareanestimated7.5millionpeopleintheUSwithstage3CKDand363,000atStage4CKDbutonly372,00ondialys