内科学教学课件：Chronic Kidney Disease

ChronicKidneyDisease1Contents

DefinitionEtiologyPathogenesisClinicalpresentationsDiagnosisTreatment23ThedefinitionofChronickidneydisease（CKD）1.kidneydamage3months，withorwithoutdecreasedGFR,asdefinedbystructuralorfunctionalabnormalities,manifestbyeither：Pathologicalabnormalities;orMarkerofkidneydamageincludingabnormalitiesinthecompositionofthebloodorurine,orabnormalitiesintheimagingtests.

2.GFR<60ml/min/1.73m2threemonths，withorwithoutkidneydamageK/DOQI，2002DefinitionCKD肾损伤（结构或功能异常）≥3个月，伴或不伴GFR下降肾脏病理损伤肾脏损伤（血，尿或影像学）GFR<60ml/min/1.73m2，伴或不伴肾损伤EndStageRenalDisease(ESRD)Uremia4ThestagesofChronicKidneyDisease

肾脏损伤：定义为病理学、尿液、血液异常或影像学检查异常KidneyDisease:ImprovingGlobalOutcomes(KDIGO)CKDWorkGroup.Kidneyinter,Suppl.2013;3:1–150.normalMAUproteinuria24h

urineALBmg/d<3030-300>300UAEug/min<2020-200>200urine

ALB/Crmg/mmol<2.5男<3.5女10-25>25微量白蛋白尿（MAU）定义MAU：尿白蛋白的排泄率超过正常范围，但低于常规方法可检测到的尿蛋白水平－K/DOQI，2002微量白蛋白尿人群的潜在危险性心血管疾病总死亡率中风肾脏疾病进展其它危险性MAU在

DM、HT

标志全身血管内皮细胞损伤Contents

Definition

EtiologyPathogenesisClinicalpresentationsDiagnosisTreatment9Etiology（病因）ObstructiveNephropathyRenalVascularDiseaseHereditarydiseasesDiabeticglomerulosclerosisPrimaryGlomerulonephritisChronicTubulo-InterstitialNephHypertensionChronicRenalFailureSecondaryGlomerulonephritis10国家年代人群调查人数患病率广州2006≥20岁631112.1%北京2006≥40岁1392510.25%上海2006≥18岁259611.8%郑州2007≥20岁185513.6%全国2012≥18岁4720410.8%NephrolDialTransplant.2009;24(4):1205-12.NephrolDialTransplant.2009;24(4):1220-26.NephrolDialTransplant.2009;24(7):2117-23.ChineseJournalofNephrology.2008,24(9):603-607.Lancet2012;379:815–822.CKDinChina每9个人中1个CKD12截止2013年底，美国每百万人中有1981.2人为ESRDTrendsintheadjustedESRDprevalence(permillion)intheU.S.population,1996-2013*Adjustedforage,sex,andrace.ThestandardpopulationwastheU.S.populationin2011.Abbreviation:ESRD,end-stagerenaldisease.UnitedStatesRenalDataSystem,2015AnnualDataReport131996-2013年美国人群中ESRD的年发病人数（单位：千）UnitedStatesRenalDataSystem,2015AnnualDataReport上海透析移植登记142015ShanghaiESRDRegistryData15162015ShanghaiESRDRegistryData不同原发病导致的ESRD,美国,1996-201317UnitedStatesRenalDataSystem,2015AnnualDataReport182015ShanghaiESRDRegistryDataESRDbyprimarydiagnosisContents

DefinitionEtiology

PathogenesisClinicalpresentationsDiagnosisTreatment19PathogenesisIntra-glomerularhyper-perfusion,hyper-pressure&

hyper-filtration

肾小球内高灌注、高压、高滤过（“三高”）---肾小球血液动力学改变Toxicityofproteinuria尿蛋白加重肾脏损伤Renin-angiotensin-aldosterone

system（RAAS）

肾素-血管紧张素-醛固酮系统作用20UremicToxinsmolecularweight：

urea，creatinine，uricacidguanidinecompounds（胍类复合物，甲基胍）phenol(苯酚),amine(胺),indole(吲哚)

largemolecularweight:

2-MG21Middlemolecularweightsolutes:

PTH（甲状旁腺激素）MW:500-5000

sympt:uremicperipheralneuropathydisorderoflipidmetabolismrenalosteodystrophy(CKD-MBD)CVDUremicToxins22Trade-offhypothesis（矫枉失衡学说）GFRP

Ca

PTHTubuleexcretionofPSerumCaparathyroidsecondaryhyperparathyriodism继发性甲状旁腺功能亢进钙磷代谢异常：低钙高磷23Disorderofnutrition&metabolismMalnutrition

(营养不良)Catabolicmetabolism分解代谢:Anabolicmetabolism合成代谢:Intake:血前白蛋白、白蛋白、胆固醇24Endocrine–metabolicdisorderEndocrinedisorders(内分泌失调)Erythropoietin↓——贫血1,25(OH)2D3↓——肾性骨病激肽-缓激肽系统（bradykinin）–扩血管，降血压血管紧张素II（Angiotensin）–血压调节前列腺素（Prostaglandin）–血压调节25Contents

Definition

EtiologyPathogenesis

ClinicalpresentationsDiagnosisTreatment261、Gastroenterologic(胃肠道)manifestations

prominentandfrequentlyencounteredanorexia(厌食)-----mostcommonnausea,vomiting,diarrheauremicgastroenteritispepticulcer,bleedingmetallictaste(uremicfetor恶臭)

ManifestationsofESRD272、Cardiovascularmanifestationhypertensionandleftventriclehypertrophy

（高血压和左心室肥大）

--mostcommoncomplicationcongestiveheartfailure（充血性心衰）pericarditis（心包炎）(incidence>50%)atherosclerosisManifestationsofESRD28CKD各阶段均可发生CVDOvertProteinuriaMicroalbuminuriaDoublingofCreatinineEndStageRenal

DiseaseCVEventsDeath3、Hemotologicmanifestationanemia（贫血）(GFR<30-40ml/min)

EPO

↓

inhibitorfactor

shortenofRBC

lifespan

shortofmaterials

lossManifestationsofESRD30KDIGO指南：成年非透析患者

Hb<10g/dl，根据Hb下降速度，对铁剂治疗的反应，需要输血的风险，使用ESA的风险，贫血症状等个体化情况决定是否ESA治疗（2C）ESA：促红细胞生成素类药物KDIGO指南.KidneyInternationalsupplements2012;2(4):279-335.Hb≥10g/dl，不建议ESA治疗（2D）KDIGO指南：成年血透患者若不及时治疗，Hb迅速跌至<8g/dl，且HD患者在Hb<9g/dl，输血风险较高。应及时使用ESA以防止Hb水平跌至<9g/dl建议在Hb9~10g/dl时及时开始ESA治疗（2B）KDIGO指南.KidneyInternationalsupplements2012;2(4):279-335.Hemotologicmanifestationplateletdysfunction

bleedingdiathesis

（出血倾向）

gastrointestinal,vaginalpericardial,intracranial

（颅内）leukocyte（白细胞）abnormalitiesManifestationsofESRD334、RespiratorymanifestationPulmonaryedema

（肺水肿）Pulmonarycongestion

（肺充血）

---“Uremiclung”Increasedpermeabilityofalveolouscap.Membrane

（肺泡毛细管膜通透性增加）Pulmonaryinterstitialedema（肺间质水肿）ManifestationsofESRD345、Neurologicmanifestationscentralnervous

uremicencephalopathy（尿毒症脑病）

（fatigue疲劳,sleepdisturbance,headache

muscularirritability,lethargy嗜睡,coma）peripheralnervous

restlesslegsyndrome（不安腿综合症）paresthesias（感觉异常）,motorweaknessparalysis（瘫痪）autonomicneuropathyManifestationsofESRD356、Dermatologicmanifestations（皮肤表现）

pallor

(苍白)

hyperpigmentation

pruritus

(瘙痒症)7、EndocrineabnormalitiesManifestationsofESRD368、Renalosteodystrophy

（肾性骨营养不良）

high-boneturnover:osteitisfibrosacystica（纤维性骨炎）

osteoporosis（骨质疏松）

osteosclerosis（骨硬化）low-boneturnover:

osteomalacia（骨软化）osteopenia（骨量减少）

ManifestationsofESRD37DignosisofCKD-MBD实验室检查异常Ca、P、iPTH、维生素D骨骼异常骨转运、骨矿化、骨骼生长、骨骼力量影像学异常血管及软组织钙化Moeetal.KidneyInt2006;69:1945-1953慢性肾脏病-

矿物质及骨异常CKD-MBD血钙血磷PTHB-AKP25羟维生素DCKD3期开始评估:血磷的新靶目标KDIGO血磷靶目标比KDOQI更严格，有较强的循证医学证据

血磷参考范围KDOQIKDIGOCKD3-4期2.7-4.6mg/dL（0.87-1.49mmol/L）2.5-4.5mg/dL（0.81-1.45mmol/L）CKD5期3.5-5.5mg/dL（1.13-1.78mmol/L）CKD5D期尽量接近正常范围KDIGOClinicalPracticeGuidelinefortheDiagnosis,Evaluation,Prevention,andTreatmentofChronicKidneyDisease-MineralandBoneDisorderKidneyInt，2009,76(Suppl113),S1－S2

血钙的新靶目标KDIGO将血钙正常范围上限提高至2.50mmol/L循证医学的证据证明该靶目标是安全的血钙参考范围KDOQIKDIGOCKD3-4期实验室正常范围实验室正常范围CKD5期8.4-9.5mg/dL（2.1-2.37mmol/L）CKD5D期KDIGOiPTH的新靶目标KDIGO:CKD5期,iPTH应维持在正常上限的2-9倍KDOQIKDIGOCKD3期35-70pg/Ml（3.85-7.7pmol/L）正常范围CKD4期70-110pg/mL（7.7-12.1pmol/L）CKD5期150-300pg/mL（16.5-33.0pmol/L）CKD5D期130-600pg/ml骨特异性碱性磷酸酶（ALP）KDIGOALP可用于评价骨骼病变CKD3期患者应检测一次ALPCKD5期患者应每年检测一次ALP没有给出靶目标范围检测方法和标本采集较PTH方便9、Infection(oneofthemajorcauseofdeath)immunefunctionisdepressed10、Metabolicacidosis（代谢性酸中毒）IncreasecardiovasculareventsIncreasemortalityinCKDpatientsManifestationsofESRD4411、Fluid,electrolyte

disturbancesodium（钠）andwaterhypernatremia，hyponatremiapotassium（钾）Hyperkalemia，hypokalemiaManifestationsofESRD45SeverearrhythmiaCardiacarrestEKG：HighpeakTwave

ProlongedP-R

WidenQRSwaveHyperkalemia（高钾血症）46AtlasofAnesthesia:CriticalCare47Contents

Definition

EtiologyPathogenesis

ClinicalpresentationsDiagnosisTreatment48DiagnosticProcedureRenalfailure(yesorno)DifferentiateAKIorCKDLookforreversiblefactorsAnalyzethestageofCKDAnalyzeifthereiscomplicationsDiagnoseprimary/secondarydiseaseGFR↓Cr,BUNyesLonghistoryUrinevol.atnightSmallkidneyAnemiaCa,PCKDPre-renalfactorsPost-renalfactorsrenalparenchymafactorsVascularfactorsDrug?Infection?Infection,CVD,anemia,malnutrition,osteodystrophy,hyperkelamia,uremicencephalopathy49120mmol/L120mmol/LsCr130mL/min30mL/mineGFRAgeGenderBodyweightMusclemassRaceReproductioncourtesyofPEStevensScr受多种因素影响CG公式（CockcroftGault）male

Ccr=(140-age)×bodyweight/Scr（mg/dl）×72female

Ccr=maleCcr×0.85CG公式对肥胖和浮肿病人高估了其GFRESTIMATIONOFGFRESTIMATIONOFGFR

MDRDStudy

GFR（ml/min/1.73m2）=186×（Scr/88.6）－1.154×（age）－0.203×（0.742female）normaleGFR≥90ml/minCKD-EPIChronicKidneyDiseaseEpidemiologyCollaborationCKD-EPIcreat公式a值：根据性别与人种分别采用如下数值：

黑人

女性=166

男性=163

白人及其他人种

女性=144

男性=141

b值根据性别不同分别采用如下数值:

女性=0.7

男性=0.9

c值根据年龄与血清肌酐值的大小分别采用如下数值：

女性

血清肌酐≤0.7mg/dL=-0.329

血清肌酐>0.7mg/dL=-1.209

男性

血清肌酐≤0.7mg/dL=-0.411

血清肌酐>0.7mg/dL=-1.209CKD-EPI

GFR=a×(serumcreatinine/b)c×(0.993)ageAnnInteralMed2009,May52012CKD-EPIcreatinine-cystatinC公式CKD-EPIcystatinC公式2012CKD-EPIcystatinC血cysC血cysC血ScrInkerLA,etal.NEnglJMed.2012Jul5;367(1):20-9Contents

Definition

EtiologyPathogenesis

Clinicalpresentations

Diagnosis

Treatment55CKD

deathStagesinProgressionofCKDandTherapeuticStrategiesComplicationsScreening

forCKD

riskfactorsCKDrisk

reduction;

Screeningfor

CKDDiagnosis

&treatment;

Treat

comorbid

conditions;

Slow

progressionEstimate

progression;

Treat

complications;

Preparefor

replacementReplacement

bydialysis

&transplantNormalIncreased

riskKidney

failureDamageGFRDelayprogression&reduceCVSRiskPreventUraemicComplicationsModifycomorbitiesPrepareforRRTACEinhibitorsMalnutrition/AnaemiaCardiacdiseaseEducationBPcontrolCVSdiseaseVasculardiseaseInformedchoiseofRRT/conservativemanagementGlucosecontrolCalciumPhosphatePTHDruginteractionsTimelyaccessplacement/TransplantListSmokingcessationAcidosisNeuropathy/RetinopathyTimelyinitiationofRRTEarlydetectionofCKDTreatmentPrimarydiseaseandreversiblefactorstreatmentTreatmentofcomplicationsofESRDBloodpurificationRenaltransplantation58DiettherapyEnoughcalorieintake:30-35kcal/kg/dLowproteindiet:（Non-Dialysis，Non-Diabetes）CKD1-2stage0.8g/kg/dCKD3stage0.6g/kg/dCKD4-5stage0.4g/kg/dEssentialaminoacidsupplement59Treatmentofcomplications

1、Hypertension:目标血压值130-139/80-85mmHg——2009

ESH指南高血压高危、低危靶目标均为SBP<140mmHg——2013

ESH指南

60不同人群靶目标血压不同BPTargetinCKD中国高血压防治指南伴有慢性肾脏疾病、糖尿病，或病情稳定的冠心病或脑血管病的高血压患者治疗更宜个体化，一般＜130/80

mmHg2013ESH/ESC高血压管理指南无论是高危还是低危的高血压患者，收缩压的目标值全部是＜140mmHg除糖尿病患者舒张压靶目标值调整到85mmHg外，其他患者的舒张压靶目标值均为＜90mmHg

61EuropeanHeartJournal.doi:10.1093/eurheartj/eht151AntihypertensiveDrugsrestrictionofsodiumACEI/ARBCCBβ-blocker-blockerdiuretic62RestrictionofwaterandsodiumFurosemideVasculardilationDigoxins2、HeartFailure63BloodpurificationCorrectionofelectrolytesandacid-basedisturbanceImprovementofanemiaPericarditis:IncreasedialysisfrequencyortimeHeparinfreedialysisSurgery643、Anemia:Recombinanthumanerythropoietin 50-100u/kgtiw,ih target:Hb110-120g/L,Hct30-35%Iron:ivorpoFolicacid654、CKD-MBD:RecovertheimbalanceofCa,P（calciumphosphatePTH）

restrictionofintake phosphatebindingVitaminDsupplementPartialparathyroidectomy66FluidandelectrolytesNaintake:3g/dpatientswithhypertension,edema,orheartfailureshouldrestrainsodiumintakeMetabolicacidosis Sodiumbicarbonate675、Fluid,electrolytesandacid-basedisturbanceHyperkalemia

Identifytreatablecauses10%calciumgluconateinject:10-20ml50%gluconate50-100mli.v.+insulin6-12u5%sodiumbicarbonateInfusion:250mlUseexchangeresinHemodialysisorperitonealdialysis68ControlinfectionAdjustantibioticdosageaccordingtoGFRRenaltoxicitydrugs：NoTraditionalChinesemedicineOtherTherapy69RenalReplacementTherapy

(RRT,肾替代治疗)HemodialysisPeritonealdialysisRenalTransplantation70血液透析Hemodialysis71Hemodialysis72血液透析需要每周进行2-3次，每次3－5个小时GFR<10-15ml/min血液透析是利用血透机来净化血液，机器上有一个特殊的滤器，叫做透析器，它就相当于一个人工肾脏，清除身体里的废物和多余的水分。73腹膜透析PeritonealDialysis74HowisPeritonealDialysisDone?PeritoneumPeritoneal

Dialysis

SolutionBagwithFreshSolutionImplanted

CatheterBagforUsedSolutionPeritonealdialysis

isdonebyfillingspeciallycomposedperitonealdialysissolutionintotheabdominalcavity.Thesolutetransferbetweenbloodand

thesolutionhappensbydiffusion.Thewaterremovalfromthepatientis

anosmoticprocess.75

“腹透液”无菌液体灌进腹腔血液中废物和多余水分就通过腹膜进入腹透液里把含有废物和多余水分的透析液放出来再灌进去新的腹透液，透析的过程就又开始每一次引流和灌入，称为“换液”76新鲜透析液透出液管路腹膜透析有两种连续性不卧床腹膜透析(CAPD)手工操作每天4次手工换液一周7天自动化腹膜透析(APD)机器操作夜间自动换液一周7天77肾移植RenalTransplantation78LocationofaKidneyTransplantAortaConnectionof

RenalArteryand

VeintothePelvic

VesselsLiverKidneyTransplant

in