肝硬化急性肾损伤

AcuteKidneyInjuryinLiverCirrhosis肝硬化急性肾损伤Diagnostics2024-05-22文献发表信息发表类型：JournalArticle、Review期刊：Diagnostics发表日期：13-7-2023关键词：肝肾综合征作者单位：1.DepartmentofTransplant,DivisionofKidneyandPancreasTransplant,MayoClinic,Jacksonville,FL32224,USA;attieh.rosemary@文献重点信息摘取急性肾损伤（AKI）在肝硬化患者中很常见，影响了近20%的患者。虽然多种病因可导致AKI，但肾前氮质血症似乎是AKI最常见的病因。无论病因如何，AKI与较差的生存率相关，在肝肾综合征（HRS）和急性肾小管坏死（ATN）患者中观察到的结果最差。尿液生物标志物和护理点超声（POCUS）等诊断工具已经可用，它们将在不久的将来用于区分这些患者的AKI的不同原因和AKI的直接管理。在这次更新中，作者将回顾肝硬化患者AKI的这些新分类、治疗建议和诊断工具。主要背景肾功能障碍给肝病患者带来了沉重的负担。急性肾损伤（AKI）影响30-50%的肝硬化住院患者，并导致急性肾脏疾病（AKD）和新发慢性肾脏疾病（CKD）的发展。AKI还与肝硬化患者的许多并发症有关，包括住院时间延长和生存率下降。在本文的工作中，作者旨在综述肝硬化患者AKI的定义、分期、病因和流行病学。作者还讨论了肝肾综合征的病理生理学，并介绍了其诊断和治疗策略的最新进展。主要背景—相关文献参考(PMID:33553656)标题：肝硬化住院患者的急性肾损伤：危险因素、肾损伤类型和生存率。期刊：JGHopen:anopenaccessjournalofgastroenterologyandhepatology(影响因子：None)发表日期：2021-02-01第一单位：DepartmentofGastroenterologySriramChandraBhanjaMedicalCollegeandHospitalCuttackIndia.KeyMessages：与无AKI患者相比，AKI患者白细胞计数高，血清尿素和肌酐高，Child-Turcotte-Pugh高，终末期肝病模型（MELD）评分高（P < 0.001），住院时间长，28天和90天生存率低（P < 0.001）。AKI患者在28天和90天时急性肝衰竭和慢性肝衰竭的发病率增加，住院时间延长，生存率降低。主要背景—相关文献参考(PMID:27720915)标题：肝硬化患者急性肾损伤分期系统的验证及其与急慢性肝功能衰竭的相关性。期刊：Clinicalgastroenterologyandhepatology:theofficialclinicalpracticejournaloftheAmericanGastroenterologicalAssociation(影响因子：12.6)发表日期：2017-03-01第一单位：UnitofHepaticEmergenciesandLiverTransplantation,DepartmentofMedicine,UniversityofPadova,Padova,Italy.KeyMessages：共有290名患者患有AKI（53%；197名患者患有1期疾病）；根据诊断时的SCr水平确定AKI分期。定义HRS诊断标准最近也被重新定义，以反映HRS是一系列疾病，而不是一个单一的实体（表1）。Table1：肝硬化HRS的新定义和分期系统。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的鉴别诊断表2总结了肝硬化患者肾损伤的鉴别诊断及其潜在原因。Table2：肝硬化AKI的鉴别诊断及潜在原因、诊断和处理。(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的鉴别诊断表2总结了肝硬化患者肾损伤的鉴别诊断及其潜在原因。Table2：肝硬化AKI的鉴别诊断及潜在原因、诊断和处理。(2)EtiologyPotentialCausesandPathophysiologyDiagnosisManagementAcuteInterstitialnephritis(AIN)FluoroquinoloneuseforSBPprophylaxisorproton-pumpinhibitor(PPI)useforGIprophylaxisClinicalhistory,sterilepyuriaonurinalysis,whitebloodcellcastsonurinemicroscopyWithdrawalofoffendingagentObstructiveuropathyMidodrine(alphaagonistusedforbloodpressuresupportinHRS)Physicalexam,bladderscan,POCUS,renalultrasonographyWithdrawalofoffendingmedication,urinarycatheterization常规诊断工具表3总结了肾前氮质血症（PRA）、ATN和HRS的主要诊断特征。Table3：肝硬化患者AKI的三个主要原因之间的差异。(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常规诊断工具表3总结了肾前氮质血症（PRA）、ATN和HRS的主要诊断特征。Table3：肝硬化患者AKI的三个主要原因之间的差异。(2)PRAATNHRSUrineBiomarkers(NGAL)+++++新型生物标志物表4讨论了最重要的新型生物标志物及其效用和陷阱。Table4：诊断肝硬化AKI的新生物标志物。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无创血流动力学测量POCUS可以准确测量IVC直径和IVC收缩率百分比，这是右心房压力测量的替代品，因此可以区分体积耗尽和体积充满状态（表5）。Table5：下腔静脉（IVC）的POCUS评估及其与中心静脉压（CVP）的相关性。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支持性护理图1展示了肝硬化AKI初始管理的拟议算法。Figure1：肝硬化和腹水患者AKI初始管理的建议算法。需要仔细的临床检查，并通过使用护理点超声（POCUS）或床边超声心动图测量下腔静脉（IVC）直径和收缩性来频繁评估血管内容量状态，以避免过度输注白蛋白导致容量过载。本文献摘要摘要：急性肾损伤（AKI）在肝硬化患者中很常见，影响了近20%的患者。虽然多种病因可导致AKI，但肾前氮质血症似乎是AKI最常见的病因。无论病因如何，AKI与较差的生存率相关，在肝肾综合征（HRS）和急性肾小管坏死（ATN）患者中观察到的结果最差。近年来，肝硬化AKI出现了新的定义和分类。关于在这些患者中使用白蛋白和特利加压素的益处和缺点，也有了更多的知识。尿液生物标志物和护理点超声（POCUS）等诊断工具已经