慢性肾脏病患者疾病管理.ppt

MANAGEMENTOFTHEPATIENTWITHCHRONICKIDNEYDISEASE,MedicineHousestaffConference2/13/2009MargaretAKiserMDPhD,Outline,ChronicKidneyDiseaseDefinitionsEpidemiologyScreeningforCKDTreatingComplicationsofAdvancedCKDHypertensionControlofvolumeAlterationsinbonemetabolismAnemiaNutritionHyperkalemiaSuggestedK-DOQIactionplanbasedondiseaseseverityWhentoreferandwhySlowingProgressionofCKDEvidencesupportingantihypertensiveuseCardiovascularRiskModificationGettingthewordout,WhatisChronicKidneyDisease?,DefiningCKD,Kidneydamagefor3monthsasdefinedbystructuralorfunctionalabnormalitiesofthekidney,withorwithoutdecreasedGFR,manifestbyeither:Pathologicalabnormalities;orMarkersofkidneydamage,includingabnormalitiesinthecompositionofthebloodorurine,orabnormalitiesinimagingtestingGlomerularFiltrationRate(GFR)90*10,2595.82MildGFR6089*5,3007,100343ModerateGFR3059*7,5533.34SevereGFR15293630.25Kidneyfailure15ordialysis3000.112.413.4,GFRPrevalenceinUSPop.*StageDescription(mL/min/1.73m2)N(1,000s)%,*Populationof177millionadultsageover20*withpresenceofproteinuriaorhematuria+/-structuralchanges*donotneedproteinuriaorhematuria,justGFR60yrsFamilyhistoryofkidneydiseaseExposuretodrugsorproceduresassociatedwithanacutedeclineinkidneyfunctionKidneydonorsandtransplantrecipients,(AJKD,39,2002,pS214),RelationshipofSerumCreatininetoGFR,EstimationofGFR,GFRcanbeassessedbytherenalclearanceofasubstanceClearanceofsubstanceX(Cx)=UxVx/SxRecallGFR*Sx=UxVx(amountfiltered=amountexcreted)Cx=UxV/SxCx=GFRTwoimportantassumptions:MarkerneithersecretedorabsorbedSteadystateExamplesofmarkers:inulin,iothalamate,iohexol,serumcreatinine,cystatin-C,CalculationofGFR,MethodsofcalculationCockcroft-GaultformulaMDRDformula/modifiedMDRD,TheCockcroft-Gaultcalculation,GFRml/min/1.73m2=(140-age)xLeanBWKg72xScreatininemg%(x0.85forFemales),MDRDGFRFormula*170 xSCr-0.999xAge-0.176x0.762iffemalex1.180ifblackxAlb+0.318ModifiedMDRDFormula186.338xSCr-1.154xAge-0.203x1.212ifblackx0.742iffemale,MDRDGFR,*FromLeveyetal,1999AnnInternMed130:461-470,(A),84F22M66M66FWt(kg)45.5104.577.271.8Screat1.2,eGFR,26.9,142.7,66.1,52.3,(CalculatedwithCockcroft-Gault),UrineProtein/CreatinineRatio,BasedontheassumptionthatinthepresenceofstableGFR,urinecreatinineandproteinexcretionconstantGinsbergetalfirstdemonstratedastrongcorrelationbetweensingleUrineP/Cand24hurinein46ambulatorypatientsatasinglecenter,r=0.97ImportantcaveatsLeanbodymassTimingofurinecollection,Relationshipofspotand24urineprotein,GroupA:Lowcreatinineexcretion,slope=1.11GroupB:IntermediateCrexcretion,slope=0.97GroupC:HighCrexcretion,slope=0.77,Fig1Correlationbetweenlnspotmorningurineprotein:creatinineratioandlog24hoururinaryproteinin177non-diabeticpatientswithchronicnephropathiesandpersistentclinicalproteinuria,PhysiologicChangesinChronicKidneyDisease,IncreasedsinglenephronGFRAfferentarteriolarvasodilationIntraglomerularhypertensionLossofglomerularpermselectivityInabiltytoappropriatelydiluteorconcentratetheurineinthefaceofvolumechallenge,AnatomicandHistologicFeaturesDuetoGlomerularHypertension,GlomerularhypertrophyFocalsegmentalglomerulosclerosiswithhyalinosisInterstitialfibrosisVascularsclerosisEpithelialfootprocessfusion,PathogenesisofSecondaryGlomerulosclerosis,NephronMass,GlomerularVolumeandGlomerularHypertension,EpithelialCellDensityandFootProcessFusion,GlomerularSclerosisandHyalinosis,PrimaryInsult,Proteinuria,HypertensioninCKD,RecommendationsforAnti-hypertensivesinPatientswithChronicKidneyDiseaseTreatmentisindicatedatanystageofthediseaseUsedrugsthatlowerglomerularcapillarypressure(ACEinhibitors,ARB,verapamilanddiltiazem)Goalistokeepthebloodpressure130/80mmHg(120SBPinDM),EffectsofVariousAnti-hypertensivesonGlomerularCapillaryPressure,AfferentArteriole,EfferentArteriole,DihydropyridinesNifedipineFelodipineAmlodipine,Vasodilate,Pressure,ARBVerapamilDiltiazem,Vasodilate,Pressure,Vasoconstrict,ACE-I,NumberofMedicationstoAchieveGoalBPin5TrialsofDM/RenalDisease,Bakris.JClinHypertens1999;1:141.,AHierarchyofAgents,ACE-IARB,-BlockersThiazideDiuretics,Vasodilators-BlockersCentralAgents,CCBs,MorePreferred,LessPreferred,VolumeManagement-Diuretics,%FilteredNa+SiteofActionDiureticExcretedNa+-K+-2Cl-carrierFurosemideinLoopofHenleBumetanide20%TorsemideEthacrynicacidNa+-Cl-carrierThiazides3-5%inthedistaltubuleMetolazoneNa+channelintheAmiloride1-2%corticalcollectingTriamtereneductSpironolactone(indirect),NatriureticResponsetoFurosemideatDifferentLevelsofRenalFunction,GFR150ml/min,GFR15ml/min,1250mEq,125mEq,250mEq,25mEq,DiureticTolerance,TypeI:Short-termDecreaseintheresponsetoadiureticafterthefirstdoseTeleologically-appropriateresponsetovolumedepletionTypeII:Long-termHypertrophyofdistalnephronsegmentsallowinggreatersodiumresorption,AlgorithmforDiureticUse,RenalInsufficiencyCrCl50,LoopDiureticDetermineEffectiveDose:5-10XUsualDoseAdministerasFrequentlyasNecessary,ThiazideAccordingtoCrCl50ml/min50-100mg/50-100mg/25-50mg/daydayday,ADD,AddDistalDiureticDrug,FromBraterDGNEngJMed1998;339:387,AlterationsinBoneandMineralMetabolism,PTH,Pi,Ca2+,RenalMass,25(OH)D3,1,25(OH)2D3,1-alpha-hydroxylase,1-alpha-hydroxylase,+,Acidosis,+,HyperparathyroidRelatedBoneDisease,ImpairedAbsorption,OsteitisFibrosaCystica,ReducedRenalMass,GFR,65,40,70pg/mlandsupplementationinstitutedifnecessary,alevelof30ng/mlisabnormaland15ng/ml,moderatetosevereTreatment2.7-4.6mg/dLCaXPhos2.7-target,initiatetreatmentwithexogenous“ActiveVitaminD”AfewpatientswithveryelevatedPTH-IvaluesmaybenefitfromCalcimimetics,(AJKD,39,2002,pS214),CalciumandPhosphorusBalance:LimitPhosphorusintaketo0.8-1.0g/d,HighPhosphorusFoodsDairyproducts(Cheese,icecream,milk),nuts,peanutbutter,biscuits,processedmeats-hotdogs,chocolate,darksodas(Coke,Pepsi),beansLowerPhosphorusChoicesCreamcheese,sourcream,Gingerale/sprite,sherbet,non-dairycreamer,UseofPhosphatebinders,Givenwithmeals,timingessentialAluminumbasedmedicines;(Basaljel,Amphogel)CalciumBasedCalciumCarbonate/MagnesiumCarbonate(Magnebind)CalciumCarbonate(Tums,Calcichew,Calcimix)CalciumAcetate(Phoslo),UseofPhosphatebinders,Theuseofcalciumbasedbindersisnowfallingoutoffavorbecauseoftherecognitionofacceleratedvascularcalcificationproposedtobeassociatedwiththem(Disputedbythemanufacturersofsame)Sevelamerhydrochloride(“Renagel”),cationicpolymer,bindsphosphatethruionexchange,canpromote/worsenmetabolicacidosisNewproductSevelamercarbonate(“Renvela”)doesnotleadtoacidosisLanthanumcarbonate(“Fosrenol”),longtermeffectsunknownVERYEXPENSIVE(Sevelamer800mgtab$1.93each,dosevaries3-9tabsaday,$173-521eachmonth,Fosrenol1000mgtab$4.87each,dose3tabsdaily,$438eachmonth),VitaminDSterols,SeveralVitaminDsterolsarenowavailabletoreplacenaturallyoccurring1,25Vitamin-D3,levelsofwhichfallwithdecliningrenalmassRocaltrol(Calcitriol,oral)Doxercalciferol(Hectoral,D2prohormone,availableinoralandparenteralforms)Paracalcitol(Zemplar),oralandparenteralformsavailable,KDOQIRecommendationsforuseofVitaminDsterols,Incompliantpatientswithstablerenalfunction,Initiate“ActiveVitaminD”(1,25-OHD3)supplementswhen:25-(OH)D30pg/ml,PTH-Itarget,Ca4.6Calcitriol0.25-1.0mcgpoqd(Rocaltrol)Doxercalciferol2.5-10mcgpotiw(Hectoral)Paracalcitol1-4mcgpoqd(Zemplar)CheckCaandPhosqmonthx3monthsthenq3monthsandcheckPTH-Iq3monthsMonitorcloselybecauseofthesignificantriskofdevelopinghypercalcemia,(AJKD,39,2002,pS214),TheCalcimemetics,CalciumSensingReceptor(CaR),Cinacalcet(SensitizesCaRtoCa2+),Nucleus,VDR,VitaminD,SerumCalcium,PTH,Inhibitory,Stimulatory,CellularProliferation,Theparathyroidcell,TreatmentofSecondaryHyperparathyroidism,CalcimimeticagentsRapidonset(hours)InhibitPTHsecretionInhibitPTHsynthesisInhibitparathyroidcellularproliferationDecreaseserumcalcium,VitaminDSterolsActongenomicreceptorSlowonset(daystoweeks)InhibitPTHsynthesisIncreaseserumcalcium,Phosphorus,Ca2+,1,25(OH)2D3(UseCautiously),NewParadigminTreatmentofSecondaryHyperparathyroidism,Non-calciumBasedBinders,Cinacalcet,PTH,ComplicationsofLongTermCalciumandPhosphorusimbalance,TertiaryhyperparathyroidismRenalosteodystrophyDemineralizationBonepainFracturesSystemictoxicityCutaneous-CalciphylaxisCardiovascular,acceleratedvascularcalcificationNervous,Parathyroidectomy,IndicationBio-IntactPTH800pg/mLrefractorytomedicaltherapySeverehypercalcemiaProgressivehighturnoverbonediseaseComplicationsMayresultinexcessivelowPTHlevelsSymptomatichypocalcemiaRiskforinjurytorecurrentlaryngealnerve,AnemiaofChronicKidneyDisease,DevelopswhentheGFRdecreasesto200,TSAT20%OralagentsChromagen:33%ironFerroussulfate:20%ironNiferex(PolysaccharidewithVitC):150mgelementalironFerrousfumurate:33%ironFerrousgluconate(Fergon):12%ironOralagentsdonotworkwell,primarilyb/oilltoleratedGIsideeffects,Nutrition,Balancingtheimpactofdecreasedproteinintakeontherateofprogressionofrenaldisease,againsthypoalbuminemiaandmalnutritionCanwerestrictproteinintakesufficiently,withoutleadingtomalnutrition,especiallyimportantinpatientswitheGFR/=1.7mg/dl(M)and/=1.4(F)PoorlycontrolledHTNDiabetesmellituswithatypicalrenalmanifestationsProteinuriaornephroticsyndromewithoutretinopathyRenalinsufficiencywithoutproteinuriaorretinopathySuddenonsetofnephroticsyndromeorrapidlychangingserumcreatinineSystemicdiseaseassociatedwithrenalinvolvementHeavyproteinuriaUrine-sedimentabnormalitiesPriortoonsetofuremicsymptoms,GoalsofEarlyReferral,Patienteducation,soonMedicarereimbursementforCKDeducationChoiceofmodality:HDvsPDvsTransplantPlanningofvascularaccessifHDisthechosenint