RTA-美国著名医学专家内部资料课件

RenalTubularAcidosis:

WhentoSuspectand

HowtoTreat?TejK.Mattoo,MDProfessorofPediatricsChief,PediatricNephrology&HypertensionChildren’sHospitalofMichiganDetroit,MIRenalTubularAcidosisInabilitytoReclaimfilteredHCO3inproximaltubule(HCO3filteredinadults=4500mEq/day)and/orExcreteH+inthedistaltubuleNon-volatileacidsthatneedfiltration/excretion(NVAgeneration=0.8-1.0mEq/kg/day)Types:I,II,III,IVProximalRTA(TypeII)DiminishedrenalthresholdforHCO3reabsorption NormalFeHCO3 <5% PRTA >20%ProximalRTAIsolatedproximalRTASporadic:Infancyandtransient(NHE3)Hereditary:PersistentRecessive(kNBC-1)-SLC4A4Dominant(NHE)-SLC9A3FanconisyndromePrimaryGenetic(cystinosis)SporadicSecondarySecondaryCausesofFanconiSyndromeDysproteinemicstatesGalactosemiaHereditaryfructoseintoleranceLowe'ssyndromeMetachromaticleukodystrophyMethylmalonicacidemiaMonoclonalgammopathyMultiplemyelomaPyruvatecarboxylasedeficiencyTyrosinemiaWilson'sdiseaseAssociatedwithchronichypocalcemiaandsecondaryhyperparathyroidismVitaminDdeficiencyorresistanceVitaminDdependencyDrug-inducedortoxin-inducedArginineGentamicinGlue(toluene)LeadMaleicacidMedullarycysticdiseaseMercuryMethyl-3-chromoneOutdatedtetracyclinesRenaltransplantationSjogren'ssyndromeStreptozotocinTubulointerstitialdiseasesOtherrenalandmiscellaneousdiseases

AmyloidosisBonefibromaNephroticsyndromeOsteopetrosisParoxysmalnocturnalhemoglobinuriaSevereburnsDistalRTA(TypeI)InabilityofthedistalrenaltubuletolowerurinepHto<5.5inpresenceofsystemicmetabolicacidosis(mostlyduetoinabilitytosecreteH+)DistalRTA

IsolateddistalRTASporadicHereditaryRecessive Deafness+(β1subunitofH-ATPase)-ATP6V1B1 Deafness-(A4H-ATPase)-ATP6V0A4 Osteopetrosis+(CAII)-CA2Dominant(Cl/HCO3-AE1)-SLC4A1SecondarydistalRTASecondaryCausesofDistalRTAAssociatedwithotherdisordersSicklecelldiseaseOsteopetrosisCirrhosisAssociatedwithotherrenaldiseaseNephrocalcinosisPyelonephritisOstructiveuropathyRenaltransplantAuto-immunedisordersSjogren’ssyndromeRheumatoidarthritisLESDrugs/toxins,e.g.amphotericinB,lithium,ifosfamideHypercalcaemiaorhypercalciuriaHyperglobulinemiaDistalRTA1.Secretorydefect(classic)inabilitytocreateandmaintainH+gradientacrosstheluminalmembrane2.Back-leakdRTA(Gradientdefect)AbilitytosecreteH+isretainedThegradientnotmaintainedduetobackdiffusionExample:AmphotericinB3.Voltage-dependentInabilitytomaintainanegativeintraluminalvoltage-noH+secretionDefect-principalcellsExample:ObstructiveuropathyTypeIIIRTADecreasedHCO3reclamationinPCT+DiminishedurineacidificationbyDCTOsteopetrosis/Marblebraindisease(Guibaud-Vainselsyndrome)CAIIdeficiency/Autosomalrecessive(CA2)HyperkalemicRTAHyperkalemicdistalRTA(TypeIRTA) (voltage-dependanttypeofdistalRTA)TypeIV(diminishedrenaltubularNH3formation)(UrineacidificationisnormalinTypeIVRTA)TypeIVRTAPrimary(Mostcommon,transient,mostlyininfancy)Secondary-PrimarymineralocorticoiddeficiencySelectivealdosteronedeficiencyCombinedwithglucorticoiddeficiencyHyporeninemic

hypoaldosteronismAldosteroneresistancePseudohypoaldosteronismtype1Pseudohypoaldosteronismtype2(Gordonsyndrome)DrugsACEIAmiloride/spironolactone/TriamtereneSMZ/TMPChronicheparintreatmentWhentoSuspectRTA?Normalanion-gapmetabolicacidosiswithnogastrointestinalsymptoms(highchloridewithlowbicarbonate)WhentoSuspectRTAFailuretothriveIncidentalfindingsonbloodchemistryRickets(nutritionalorrenal)HematuriaPolyuria/polydipsia/constipationNephrocalcinosis/nephrolithiasisMusculoskeletalweaknessIleus/vomitingUTIRenalFailureWhenitmaylooklikeRTALowserumHCO3becauseofcompensationforrespiratoryalkalosis3Year-old-maleFamilymovedtoMichiganChildtreatedforProximalRTAforoneyear,HCO3dose=3mEq/kg/day)BloodchemistrybeforebicarbonatetherapywasstartedNa+ 141mEq/LK+ 4.4mEq/LChloride 107mEq/LHCO3 18mEq/L3Year-old-maleCapillarybloodgasPH 7.45PCO2 18.7PO2 110.5BE -8HCO3 13(Respiratoryalkalosiswithpartialrenalcompensation)3Year-old-maleFinaldiagnosisbygenetics/neurologyMitochondrialdisorderUnwinRJ.Therenaltubularacidosis.JournaloftheRoyalSocietyofMedicine(2001)94:221-225

DecreasedrenalHCO3threshold(lowreabsorptivecapacityforHCO3)eg,16meq/LUrinepHinappropriatelyelevatedifplasmaHCO3above16meq/L,sincefilteredHCO3loadexceedsthereducedreabsorptivecapacityWhenplasmaHCO3concdecreasestolowlevel,urinepHdecreasesbelow5.5TreatmentAlkaliadministration(citrateorbicarbonate)Usualstartingdose1-3mEq/kg/dayDoseincreasetitratedtoserumHCO3AppropriateadditionaltreatmentforsecondaryRTATreatmentProximalRTAHCO3requirmentusually>10mEq/kg/dayK+supplementsHydrochlothiazide/IndomethacinTreatmentDistalRTAHCO3requirement1-3mEq/kg/dayK+supplementationTreatmentTypeIVRTAAlkaliadministrationLooporthaizidediureticDietaryK+restriction+MinerallocorticoidConclusionsRTAhasacomplexbutincreasinglyclearpathophysiologyDiagnosiscanbemadeearly,particularlyinthosewithahighindexofsuspic