IgA肾病结合内科ppt课件.ppt

IgA 肾病肾病 IgA nephropathy Hebei medical university Xu qingyoudefinitionIgAnephropathyisthemostcommonglomerulonephritisthroughouttheworld.PrimaryIgAnephropathyischaracterizedbydepositionoftheIgAantibodyintheglomerulus.definition IgA nephropathy remains the one of the most common,if not the most common,glomerular lesions of all the forms of glomerulonephritis.IgA nephropathy(alsoknownasIgA nephritis,IgAN,Bergers disease)isaformofglomerulonephritis(inflammationoftheglomeruliofthekidney).definition IgA nephropathy was initially described in the late 1960s by Berger and Hinglais,and patients were described on the basis of the finding of predominant IgA deposition(and,to a lesser extent,other immunoglobulins)in the mesangium with a mesangial proliferation,and with clinical features that span the spectrum from asymptomatic hematuria to repidly progressive glomerulonephritis.Berger J,Hinglais N.J Urol Nephrol 1968,74:694definition The distribution of IgA nephropathy varies in the different geographic regions throughout the world.It was the most common form of primary glomerular disease in Asia,evident in up to 30%to 40%of all biopsies,20%in Europe,and 10%of all biopies performed for glomerular disease in North America.30%to40%10%20%Signs and symptoms Theclassicpresentation(in40-50%ofthecases)isepisodicfrankhematuriawhichusuallystartswithinadayortwoofanon-specificupperrespiratorytractinfection(hencesynpharyngitic)asopposedtopost-streptococcalglomerulonephritiswhichoccurssometime(weeks)afterinitialinfection.Lesscommonlygastrointestinalorurinaryinfectioncanbetheincitingagent.AlloftheseinfectionshaveincommontheactivationofmucosaldefensesandhenceIgAantibodyproduction.Loinpaincanalsooccur.Thegrosshematuriaresolvesafterafewdays,thoughmicroscopichematuriamaypersist.Theseepisodesoccuronanirregularbasiseveryfewmonthsandinmostpatientseventuallysubsides(althoughitcantakemanyyears).Renalfunctionusuallyremainsnormal,thoughrarely,acuterenalfailuremayoccur.Thispresentationismorecommoninyoungeradults.Signs and symptoms Asmallerproportion(20-30%),usuallytheolderpopulation,havemicroscopichematuriaandproteinuria(lessthan2gram/day).Thesepatientsmaynothaveanysymptomsandareonlyclinicallyfoundifadoctordecidestotakeaurinesample.Proteinuria2g/daymicroscopichematuriaSigns and symptoms Veryrarely(5%each),thepresentinghistoryis:Nephroticsyndrome(3-3.5gramsofproteinlossintheurine,associatedwithapoorerprognosis)Acuterenalfailure(eitherasacomplicationofthefrankhematuria,whenitusuallyrecovers,orduetorapidlyprogressiveglomerulonephritiswhichoftenleadstochronicrenalfailure)Chronicrenalfailure(noprevioussymptoms,presentswithanemia,hypertensionandothersymptomsofrenalfailure,inpeoplewhoprobablyhadlongstandingundetectedmicroscopichematuriaand/orproteinuria)Nephrotic syndromeAcuterenalfailureChronicrenalfailureSigns and symptoms Reich HN,et al.J Am Soc Nephrol 2007,18:3177蛋白尿蛋白尿g/dg/d6 6个月测定的均值个月测定的均值肾脏存活率Diagnosis Inchildrenandyoungeradults,thehistoryandassociationwithrespiratoryinfectioncanraisethesuspicionofIgAnephropathy.Diagnosis Foranadultpatientwithisolatedhematuria,testssuchasultrasoundofthekidneyandcystoscopyareusuallydonefirsttopinpointthesourceofthebleeding.Thesetestswouldruleoutkidneystonesandbladdercancer,twoothercommonurologicalcausesofhematuria.hematuriaDiagnosis Akidneybiopsyisnecessarytoconfirmthediagnosis.Thebiopsyspecimenshowsproliferationofthemesangium,withIgAdepositsonimmunofluorescenceandelectronmicroscopy.kidney biopsyDiagnosis OtherbloodtestsdonetoaidinthediagnosisincludeCRPorESR,complementlevels,ANA,andLDH.ProteinelectrophoresisandimmunoglobulinlevelscanshowincreasedIgAin50%ofallpatients.Diagnosis Aurinalysiswillshowredbloodcells,usuallyasredcellurinarycasts.Proteinuria,usuallylessthan2gramsperday,alsomaybepresent.OtherrenalcausesofisolatedhematuriaincludethinbasementmembranediseaseandAlportsyndrome,thelatterbeingahereditarydiseaseassociatedwithhearingimpairmentandeyeproblems.Morphology Histologically,IgAnephropathymayshowmesangialwideningandfocalandsegmentalinflammation.Diffusemesangialproliferationorcrescenticglomerulonephritismayalsobepresent.ImmunoflourescenceshowsmesangialdepositionofIgAoftenwithC3andproperdinandsmalleramountsofotherimmunoglobulins(IgGorIgM)Natural history Completeremission,anormalurinalysis,occursrarelyinadults,inabout5%ofcases.Thus,eveninthosewithnormalrenalfunctionafteradecadeortwo,urinaryabnormalitiespersistinthegreatmajority.Incontrast,3050%ofchildrenmayhaveanormalurinalysisattheendof10years.However,giventheveryslowevolutionofthisdisease,thelongerterm(2030years)outcomeofsuchpatientsisnotyetestablished.anormalurinalysisurinaryabnormalitiesadecadeortwoTherapy Patientswithisolatedhematuria,proteinuria1g/dayandnormalrenalfunctionhaveabenigncourseandaregenerallyjustfollowedupannually.Incaseswheretonsillitisistheprecipitatingfactorforepisodichematuria,tonsillectomyhasbeenclaimedtoreducethefrequencyofthoseepisodes.However,itdoesnotreducetheincidenceofprogressiverenalfailure.proteinuria1g/dayhematuriahematurianormalrenalfunctionfollowed upTherapy-steroids AsubsetofIgAnephropathypatients,whohaveminimalchangediseaseonlightmicroscopyandclinicallyhavenephroticsyndrome,showanexquisiteresponsetosteroids,behavingmoreorlesslikeminimalchangedisease.Protein3.5g/dedemaHyper-lipidemiaHypo-proteinemiaInotherpatients,theevidenceforsteroidsisnotcompelling.Shortcoursesofhighdosesteroidshavebeenproventolackbenefit.However,inpatientswithpreservedrenalfunctionandproteinuria(1-3.5g/day),arecentprospectivestudyhasshownthat6monthsregimenofsteroidsmaylessenproteinuriaandpreserverenalfunction.Therapy-Cyclophosphamide Cyclophosphamidehadbeenusedincombinationwithanti-platelet/anticoagulantsinunselectedIgAnephropathypatientswithconflictingresults.Also,thesideeffectprofileofthisdrug,includinglongtermriskofmalignancyandsterility,madeitanunfavorablechoiceforuseinyoungadults.However,onerecentstudy,inacarefullyselectedhighriskpopulationofpatientswithdecliningGFR,showedthatacombinationofsteroidsandcyclophosphamidefortheinitial3monthsfollowedbyazathioprineforaminimumof2yearsresultedinasignificantpreservationofrenalfunction.Otheragentssuchasmycophenolatemofetil,ciclosporinandmizoribinehavealsobeentriedwithvaryingresults.Therapy-omega-3 fatty acids AstudyfromMayoClinicdidshowthatlongtermtreatmentwithomega-3fattyacidsresultsinreductionofprogressiontorenalfailure,without,however,reducingproteinuriainasubsetofpatientswithhighriskofworseningkidneyfunction.However,theseresultshavenotbeenreproducedbyotherstudygroupsandintwosubsequentmeta-analyses.However,fishoiltherapydoesnothavethedrawbacksofimmunosuppressivetherapy.Also,apartfromitsunpleasanttasteandabdominaldiscomfort,itisrelativelysafetoconsume.Therapy-ACEI,ARB Low-proteindietandoptimalcontrolofbloodpressure.Thechoiceoftheantihypertensiveagentisopenaslongasthebloodpressureiscontrolledtodesiredlevel.However,AngiotensinconvertingenzymeinhibitorsandAngiotensinIIreceptorantagonistsarefavouredduetotheiranti-proteinuriceffect.