肝硬化急性腎損傷

AcuteKidneyInjuryinLiverCirrhosis肝硬化急性腎損傷Diagnostics2024-05-22文獻(xiàn)發(fā)表信息發(fā)表類型：JournalArticle、Review期刊：Diagnostics發(fā)表日期：13-7-2023關(guān)鍵詞：肝腎綜合征作者單位：1.DepartmentofTransplant,DivisionofKidneyandPancreasTransplant,MayoClinic,Jacksonville,FL32224,USA;attieh.rosemary@文獻(xiàn)重點信息摘取急性腎損傷（AKI）在肝硬化患者中很常見，影響了近20%的患者。雖然多種病因可導(dǎo)致AKI，但腎前氮質(zhì)血癥似乎是AKI最常見的病因。無論病因如何，AKI與較差的生存率相關(guān)，在肝腎綜合征（HRS）和急性腎小管壞死（ATN）患者中觀察到的結(jié)果最差。尿液生物標(biāo)志物和護(hù)理點超聲（POCUS）等診斷工具已經(jīng)可用，它們將在不久的將來用于區(qū)分這些患者的AKI的不同原因和AKI的直接管理。在這次更新中，作者將回顧肝硬化患者AKI的這些新分類、治療建議和診斷工具。主要背景腎功能障礙給肝病患者帶來了沉重的負(fù)擔(dān)。急性腎損傷（AKI）影響30-50%的肝硬化住院患者，并導(dǎo)致急性腎臟疾?。ˋKD）和新發(fā)慢性腎臟疾?。–KD）的發(fā)展。AKI還與肝硬化患者的許多并發(fā)癥有關(guān)，包括住院時間延長和生存率下降。在本文的工作中，作者旨在綜述肝硬化患者AKI的定義、分期、病因和流行病學(xué)。作者還討論了肝腎綜合征的病理生理學(xué)，并介紹了其診斷和治療策略的最新進(jìn)展。主要背景—相關(guān)文獻(xiàn)參考(PMID:33553656)標(biāo)題：肝硬化住院患者的急性腎損傷：危險因素、腎損傷類型和生存率。期刊：JGHopen:anopenaccessjournalofgastroenterologyandhepatology(影響因子：None)發(fā)表日期：2021-02-01第一單位：DepartmentofGastroenterologySriramChandraBhanjaMedicalCollegeandHospitalCuttackIndia.KeyMessages：與無AKI患者相比，AKI患者白細(xì)胞計數(shù)高，血清尿素和肌酐高，Child-Turcotte-Pugh高，終末期肝病模型（MELD）評分高（P?<?0.001），住院時間長，28天和90天生存率低（P?<?0.001）。AKI患者在28天和90天時急性肝衰竭和慢性肝衰竭的發(fā)病率增加，住院時間延長，生存率降低。主要背景—相關(guān)文獻(xiàn)參考(PMID:27720915)標(biāo)題：肝硬化患者急性腎損傷分期系統(tǒng)的驗證及其與急慢性肝功能衰竭的相關(guān)性。期刊：Clinicalgastroenterologyandhepatology:theofficialclinicalpracticejournaloftheAmericanGastroenterologicalAssociation(影響因子：12.6)發(fā)表日期：2017-03-01第一單位：UnitofHepaticEmergenciesandLiverTransplantation,DepartmentofMedicine,UniversityofPadova,Padova,Italy.KeyMessages：共有290名患者患有AKI（53%；197名患者患有1期疾?。桓鶕?jù)診斷時的SCr水平確定AKI分期。定義HRS診斷標(biāo)準(zhǔn)最近也被重新定義，以反映HRS是一系列疾病，而不是一個單一的實體（表1）。Table1：肝硬化HRS的新定義和分期系統(tǒng)。OldClassificationNewClassificationDiagnosticCriteriaDiagnosticCriteria.1StagesHRS-1HRS-AKIa.AbsoluteincreaseinsCr≥0.3mg/dLwithin48hand/orb.PercentincreaseinsCr≥50%usingthelastavailablevalueofoutpatientsCrwithin3monthsasthebaselinevaluea.AbsoluteincreaseinsCr≥0.3mg/dLwithin48hand/orb.PercentincreaseinsCr≥50%usingthelastavailablevalueofoutpatientsCrwithin3monthsasthebaselinevalueStage1:increaseinSCr≥0.3mg/dL(26.5μmol/L)within48horincrease≥1.5–1.9foldfrombaseline1a:SCr<1.5mg/dL1b:SCr>1.5mg/dLHRS-1HRS-AKIa.AbsoluteincreaseinsCr≥0.3mg/dLwithin48hand/orb.PercentincreaseinsCr≥50%usingthelastavailablevalueofoutpatientsCrwithin3monthsasthebaselinevaluea.AbsoluteincreaseinsCr≥0.3mg/dLwithin48hand/orb.PercentincreaseinsCr≥50%usingthelastavailablevalueofoutpatientsCrwithin3monthsasthebaselinevalueStage2:increaseinSCr2–3foldfrombaselineHRS-1HRS-AKIa.AbsoluteincreaseinsCr≥0.3mg/dLwithin48hand/orb.PercentincreaseinsCr≥50%usingthelastavailablevalueofoutpatientsCrwithin3monthsasthebaselinevaluea.AbsoluteincreaseinsCr≥0.3mg/dLwithin48hand/orb.PercentincreaseinsCr≥50%usingthelastavailablevalueofoutpatientsCrwithin3monthsasthebaselinevalueStage3:increaseinSCr≥3-foldfrombaselineorSCr≥4.0mg/dL(353.6μmol/L)withanacuteincrease≥0.3mg/dL(26.5μmol/L)orinitiationofrenal-replacementtherapyHRS-2HRS-NAKIHRS-AKDeGFR<60mL/minper1.73m2for<3monthsintheabsenceofothercausesHRS-2HRS-NAKIHRS-CKDeGFR<60mL/minper1.73m2for≥3monthsintheabsenceofothercauses3.肝硬化AKI的鑒別診斷表2總結(jié)了肝硬化患者腎損傷的鑒別診斷及其潛在原因。Table2：肝硬化AKI的鑒別診斷及潛在原因、診斷和處理。(1)EtiologyPotentialCausesandPathophysiologyDiagnosisManagementPre-renalAKIDecreasedoralintake,useofdiureticsforascites,useoflaxativesforhepaticencephalopathyprophylaxisClinicalhistory,POCUSfindings,blandurinarysedimentDiscontinuationofdiureticsandrepletionofintravascularvolumepreferablywithalbumin.Ischemicacutetubularnecrosis(ATN)Prolongedpre-renalinsult,gastrointestinalbleedleadingtohypovolemicshock,septicshockduetospontaneousbacterialperitonitis(SBP)Clinicalhistory,granularcastsonurinemicroscopyConservative,diureticsforvolumeoverloadasneeded,renalreplacementtherapy(RRT)ToxicATNNephrotoxicmedicationssuchasvancomycinorfluoroquinolonesusedforSBPtreatmentClinicalhistory,granularcastsonurinemicroscopyConservative,diureticsforvolumeoverloadasneeded,RRTBilecastnephropathy(akacholemicnephropathy)Depositionofintra-tubularbilirubincastsinsevereliverfailureSerumbilirubinlevelstypically>10mg/dL,bilirubincastsonurinemicroscopyLivertransplanttodecreaseserumbilirubinlevels,diureticsforvolumeoverloadasneeded,RRTHRS-AKI(formerlyHRS-1)Splanchnicvasodilatation,peripheralarterialvasodilation,andintenserenalvasoconstrictionDiagnosisofexclusionintheabsenceofshock,nephrotoxicdrugexposure,orstructuralkidneydisease(proteinuria>500mgperday,microhematuria>50redbloodcellsperhigh-powerfield,and/orabnormalrenalultrasonography)Albumin,vasopressors(norepinephrine,terlipressin)CirrhoticcardiomyopathyHyperdynamiccirculationleadingtorenin-angiotensin-aldosteronesystem(RAAS)andsympatheticnervoussystem(SNS)activation,cardiosuppressantssuchasnitricoxideandinflammatorycytokinesEchocardiographyLivertransplant,diureticstohelpreducepreload,vasopressorsAbdominalcompartmentsyndromeTenseascitescausingsevereintra-abdominalhypertensionandrenalveincongestionSustainedintra-abdominalpressure>20mmHgLarge-volumeparacentesisSecondaryimmunoglobulinA(IgA)nephropathyDecreaseintheexpressionofthehepaticsialo-glycoproteinreceptorleadingtodefectiveIgAglycosylationHematuriaandproteinuriaonurinalysis,renalbiopsyLivertransplantMembranoproliferativeglomerulonephritis(MPGN)HepatitisCvirus(HCV)(frequentlyleadstocryoglobulinemicvasculitis),orHepatitisBvirus(HBV)Hematuriaandproteinuriaonurinalysis,redbloodcellcastsonurinemicroscopy,positiveHCVRNAorHBVDNAbypolymerasechainreaction(PCR)Direct-actingantiviraldrugs肝硬化AKI的鑒別診斷表2總結(jié)了肝硬化患者腎損傷的鑒別診斷及其潛在原因。Table2：肝硬化AKI的鑒別診斷及潛在原因、診斷和處理。(2)EtiologyPotentialCausesandPathophysiologyDiagnosisManagementAcuteInterstitialnephritis(AIN)FluoroquinoloneuseforSBPprophylaxisorproton-pumpinhibitor(PPI)useforGIprophylaxisClinicalhistory,sterilepyuriaonurinalysis,whitebloodcellcastsonurinemicroscopyWithdrawalofoffendingagentObstructiveuropathyMidodrine(alphaagonistusedforbloodpressuresupportinHRS)Physicalexam,bladderscan,POCUS,renalultrasonographyWithdrawalofoffendingmedication,urinarycatheterization常規(guī)診斷工具表3總結(jié)了腎前氮質(zhì)血癥（PRA）、ATN和HRS的主要診斷特征。Table3：肝硬化患者AKI的三個主要原因之間的差異。(1)PRAATNHRSHypotensionYesYesYesShockNoYesNoNephrotoxinsNoYesNoAscites+/?+/?+ResponsetoIVAlbuminYesNoNoIVC<2.5cm,>50%collapse>2.5cm,<50%collapse>2.5cm,<50%collapseUrinesedimentNegativeGranularcastsNegativeFeNa<1%<1%<1%(<0.1%)UrinaryNa<10mEq/L<10>mEq/L<10mEq/L常規(guī)診斷工具表3總結(jié)了腎前氮質(zhì)血癥（PRA）、ATN和HRS的主要診斷特征。Table3：肝硬化患者AKI的三個主要原因之間的差異。(2)PRAATNHRSUrineBiomarkers(NGAL)+++++新型生物標(biāo)志物表4討論了最重要的新型生物標(biāo)志物及其效用和陷阱。Table4：診斷肝硬化AKI的新生物標(biāo)志物。BiomarkerDescriptionUtilityPitfallsCystatinC-Cysteineproteaseinhibitor-Producedbyallnucleatedcellsinthebody-Filteredbytheglomerulusandmetabolizedinthetubules-Lessinfluencedbymusclemass,age,anddiabetesthanserumcreatinine[26]-UsefulinAKIpredictionandprognostication:MELD-CystatinCimprovespredictiveaccuracyofmortality[27]-EquationsbasedonbothcreatinineandCysatinCleastbiasedinassessingtheGFRincirrhosis[28]-Severalnon-GFRdeterminantsofhigherCystatinCsuchasmalesex,greaterheightandweight,higherleanbodymass,higherfatmass,diabetes,higherlevelsofinflammatorymarkers,hyper-andhypothyroidism,andglucocorticoiduse[29,30]UrinaryNGAL-Producedbyneutrophilsandepithelialcellsincludingkidneytubularcells-Abundantlyexpressedintheurinefollowingischemicinjury-Markeroftubulardamage-Usefulfordifferentiatingpre-renalAKIfromATN(highestinATN)-GreatestaccuracyamongmonomericNGAL(mNGAL),interleukin(IL)-18,andotherconventionalurinarybiomarkersfordifferentialdiagnosisbetweenATNandothertypesofAKIwhenmeasuredatday3indecompensatedcirrhosis[31]-Predictorof90-daypatienttransplant-freesurvival[32,33]andprognosticfactorformortalityinACLF[34]-Startstoriseafter3hintheurinefollowingrenalinjury[35]-Lackofstandardization-Uncertaintyregardingthecutoffvalue-UnavailableinmanycountriesthusmakingitaresearchonlytestUrinaryKIM-1-Transmembraneproteinthatisupregulatedintheproximaltubuleandshedintheurineinresponsetoischemia-Rises2–3hfollowingkidneyinjury-UsefulindifferentiatingtypesofAKIandpredictingpatientmortality-HighestinATN-Lackofstandardization-Poorsensitivityandspecificity[36]UrinaryL-FABP-Intracellularlipidchaperoneinvolvedinlipid-mediatedprocesses-Promisingprognosticbiomarkerinpatientswithdecompensatedcirrhosis[37]-HighestinATN-LimitedstudiesindecompensatedcirrhosisUrinaryIL-18-Proinflammatorycytokine,expressedintheproximaltubularcells-Upregulatedinacuteischemicinjury-Markeroftubulardamage:higherinATNcomparedwithpre-renalazotemia,UIT,andCKD-Doesnotpredictpatientmortalityorkidneyoutcomes無創(chuàng)血流動力學(xué)測量POCUS可以準(zhǔn)確測量IVC直徑和IVC收縮率百分比，這是右心房壓力測量的替代品，因此可以區(qū)分體積耗盡和體積充滿狀態(tài)（表5）。Table5：下腔靜脈（IVC）的POCUS評估及其與中心靜脈壓（CVP）的相關(guān)性。IVCDiameter(cm)RespiratoryVariation(Collapse)CVP(cmH2O)<1.5Totalcollapse0–51.5–2.5>50%6–101.5–2.5<50%11–15>2.5<50%16–20>2.5Nochange>20支持性護(hù)理圖1展示了肝硬化AKI初始管理的擬議算法。Figure1：肝硬化和腹水患者AKI初始管理的建議算法。需要仔細(xì)的臨床檢查，并通過使用護(hù)理點超聲（POCUS）或床邊超聲心動圖測量下腔靜脈（IVC）直徑和收縮性來頻繁評估血管內(nèi)容量狀態(tài)，以避免過度輸注白蛋白導(dǎo)致容量過載。本文獻(xiàn)摘要摘要：急性腎損傷（AKI）在肝硬化患者中很常見，影響了近20%的患者。雖然多種病因可導(dǎo)致AKI，但腎前氮質(zhì)血癥似乎是AKI最常見的病因。無論病因如何，AKI與較差的生存率相關(guān)，在肝腎綜合征（HRS）和急性腎小管壞死（ATN）患者中觀察到的結(jié)果最差。近年來，肝硬化AKI出現(xiàn)了新的定義和分類。關(guān)于在這些患者中使用白蛋白和特利加壓素的益處和缺點，也有了更多的知識。尿液生物標(biāo)志物和護(hù)理點超聲（POCUS）等診斷工具已經(jīng)