2024
Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis
Moledina D, Obeid W, Smith R, Rosales I, Sise M, Moeckel G, Kashgarian M, Kuperman M, Campbell K, Lefferts S, Meliambro K, Bitzer M, Perazella M, Luciano R, Pober J, Cantley L, Colvin R, Wilson F, Parikh C. Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis. Journal Of Clinical Investigation 2024, 134: e180583. PMID: 38488004, PMCID: PMC10940080, DOI: 10.1172/jci180583.Peer-Reviewed Original Research
2023
Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis
Moledina D, Obeid W, Smith R, Rosales I, Sise M, Moeckel G, Kashgarian M, Kuperman M, Campbell K, Lefferts S, Meliambro K, Bitzer M, Perazella M, Luciano R, Pober J, Cantley L, Colvin R, Wilson F, Parikh C. Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis. Journal Of Clinical Investigation 2023, 133: e168950. PMID: 37395276, PMCID: PMC10313360, DOI: 10.1172/jci168950.Peer-Reviewed Original ResearchConceptsUrinary CXCL9External validation cohortValidation cohortControl groupAIN diagnosisDiscovery cohortKidney tissueDiagnostic biomarkersAcute interstitial nephritisCXCL9 mRNA expressionAcute kidney injuryBiopsy-confirmed diagnosisAvailable clinical testsNational InstituteKidney injuryTubulointerstitial nephritisInterstitial nephritisKidney biopsyHistological confirmationHistological diagnosisTreatment optionsLymphocyte chemotaxisCXCL9MRNA expression differencesPatientsThe Detrimental Impact of End-Stage Kidney Disease Is Not Reflected in Autopsy Reports.
Lerner G, Reynolds M, Setty S, Deeb R, Rastogi P, Moeckel G, Sanchez H, Henriksen K, Chang A. The Detrimental Impact of End-Stage Kidney Disease Is Not Reflected in Autopsy Reports. Archives Of Pathology & Laboratory Medicine 2023, 148: 74-77. PMID: 37014976, DOI: 10.5858/arpa.2022-0338-oa.Peer-Reviewed Original ResearchConceptsEnd-stage kidney diseaseKidney diseaseAutopsy reportsDie of complicationsRenal replacement therapyMicroscopic autopsy findingsCause of deathCommon CODInterpathologist variationRenal impairmentReplacement therapyAutopsy casesAutopsy findingsCardiovascular diseaseDisease findingsAutopsy assessmentCase recordsDiseaseVital statisticsDecedentsDialysisDeathReportDetrimental impactComplications
2020
Polycystin 2 is increased in disease to protect against stress-induced cell death
Brill AL, Fischer TT, Walters JM, Marlier A, Sewanan LR, Wilson PC, Johnson EK, Moeckel G, Cantley LG, Campbell SG, Nerbonne JM, Chung HJ, Robert ME, Ehrlich BE. Polycystin 2 is increased in disease to protect against stress-induced cell death. Scientific Reports 2020, 10: 386. PMID: 31941974, PMCID: PMC6962458, DOI: 10.1038/s41598-019-57286-x.Peer-Reviewed Original ResearchConceptsPolycystin-2General cellular homeostasisCell deathStress-induced cell deathPathological cell deathAutosomal dominant polycystic kidney diseaseEndoplasmic reticulum membraneCellular homeostasisCellular stressPrimary ciliaUbiquitous expressionExpression changesCell stressReticulum membraneTransient receptor potential cation channelHuman diseasesMultiple tissuesEndogenous roleDominant polycystic kidney diseaseTissue typesCation channelsPolycystic kidney diseaseDifferent pathological statesMultiple diseasesKidney disease
2019
PD-1H (VISTA)–mediated suppression of autoimmunity in systemic and cutaneous lupus erythematosus
Han X, Vesely MD, Yang W, Sanmamed MF, Badri T, Alawa J, López-Giráldez F, Gaule P, Lee SW, Zhang JP, Nie X, Nassar A, Boto A, Flies DB, Zheng L, Kim TK, Moeckel GW, McNiff JM, Chen L. PD-1H (VISTA)–mediated suppression of autoimmunity in systemic and cutaneous lupus erythematosus. Science Translational Medicine 2019, 11 PMID: 31826980, DOI: 10.1126/scitranslmed.aax1159.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritisAutoantibodiesAutoimmunityDendritic CellsHumansInflammationInterferon Type ILupus Erythematosus, CutaneousLupus Erythematosus, SystemicMembrane ProteinsMice, Inbred BALB CMice, Inbred MRL lprMyeloid CellsNeutrophilsReceptors, Antigen, T-CellSignal TransductionTerpenesUp-RegulationConceptsPlasmacytoid dendritic cellsDiscoid lupus erythematosusSystemic lupus erythematosusCutaneous lupus lesionsPD-1HLupus erythematosusLupus lesionsAutoimmune diseasesKO miceT cellsMyeloid cellsHuman systemic lupus erythematosusBALB/c backgroundCutaneous lupus erythematosusInappropriate immune responseProgression of lupusSystemic autoimmune diseaseImmune cell expansionSuppression of autoimmunityAgonistic monoclonal antibodyDeath-1 homologCutaneous lupusProinflammatory neutrophilsDendritic cellsDLE lesionsHypergranulotic dyscornification: 30 cases of a striking epithelial reaction pattern
Roy SF, Ko CJ, Moeckel GW, Mcniff JM. Hypergranulotic dyscornification: 30 cases of a striking epithelial reaction pattern. Journal Of Cutaneous Pathology 2019, 46: 742-747. PMID: 31157457, DOI: 10.1111/cup.13522.Peer-Reviewed Original ResearchConceptsBenign keratosesDistinctive histopathologic findingsHistological reaction patternEpidermolytic hyperkeratosisReaction patternsBowen's diseaseRetrospective reviewMean ageProminent granular layerHistopathologic findingsEpidermoid cystKeratin immunohistochemistryClinical impressionSeborrheic keratosisPositive stainingNeck areaAbnormal keratinizationKeratohyaline granulesUnique reaction patternReproducible findingsKeratosesCytoplasmic areaGranular layerHyperkeratosisPrevious reportsDevelopment of a 2-dimensional atlas of the human kidney with imaging mass cytometry
Singh N, Avigan ZM, Kliegel JA, Shuch BM, Montgomery RR, Moeckel GW, Cantley LG. Development of a 2-dimensional atlas of the human kidney with imaging mass cytometry. JCI Insight 2019, 4: e129477. PMID: 31217358, PMCID: PMC6629112, DOI: 10.1172/jci.insight.129477.Peer-Reviewed Original ResearchConceptsCell typesIndividual cell typesCritical baseline dataRenal cell typesMass cytometryQuantitative atlasNormal human samplesHuman kidneyRelative abundanceDevelopment of therapiesHuman kidney diseaseKidney diseaseMetal-conjugated antibodiesQuantitative interrogationScarce samplesMachine-learning pipelineDiscovery purposesFuture quantitative analysisNovel abnormalityNormal human kidneySingle tissue sectionHuman samplesRenal biopsyImmune cellsCellsUrine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis
Moledina DG, Wilson FP, Pober JS, Perazella MA, Singh N, Luciano RL, Obeid W, Lin H, Kuperman M, Moeckel GW, Kashgarian M, Cantley LG, Parikh CR. Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis. JCI Insight 2019, 4: e127456. PMID: 31092735, PMCID: PMC6542610, DOI: 10.1172/jci.insight.127456.Peer-Reviewed Original ResearchConceptsAcute interstitial nephritisAcute kidney diseasePrebiopsy diagnosisKidney biopsyKidney diseaseIL-9AIN diagnosisUrine TNFInterstitial nephritisSpecific T cell subsetsAcute tubular injuryDiabetic kidney diseaseIL-9 levelsTNF-α levelsT cell subsetsAddition of biomarkersPlasma cytokinesCytokine levelsTubular injuryHighest quartileMultivariable analysisCell subsetsUrinary TNFBlood eosinophilsGlomerular diseaseRegulated necrosis and failed repair in cisplatin-induced chronic kidney disease
Landau SI, Guo X, Velazquez H, Torres R, Olson E, Garcia-Milian R, Moeckel GW, Desir GV, Safirstein R. Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease. Kidney International 2019, 95: 797-814. PMID: 30904067, PMCID: PMC6543531, DOI: 10.1016/j.kint.2018.11.042.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseKidney diseaseKidney injuryCisplatin-induced chronic kidney diseaseCisplatin-induced acute kidney injuryToll-like receptor 2Regulated necrosis pathwaysReversible kidney injuryAcute kidney injuryChronic kidney injuryProximal tubular damageKidney injury markersDoses of cisplatinEvidence of fibrosisMechanisms of progressionEffective chemotherapeutic agentWestern blot analysisFirst doseInjury markersIntraperitoneal cisplatinSignificant nephrotoxicityTubular damageKidney functionSecond doseCisplatin administrationTelavancin-associated acute kidney injury.
Cavanaugh C, Moeckel GW, Perazella MA. Telavancin-associated acute kidney injury. Clinical Nephrology 2019, 91: 187-191. PMID: 30614441, DOI: 10.5414/cn109651.Peer-Reviewed Original ResearchConceptsAcute kidney injuryKidney injuryTubular injuryCases of AKIAcute interstitial nephritisProximal tubular injuryAcute tubular injuryHuman clinical trialsSelect infectionsInterstitial nephritisIntravenous therapyKidney biopsyKidney histopathologyHistologic changesClinical trialsHistopathologic descriptionAnimal modelsLysosomal proliferationTelavancinInjurySemi-synthetic derivativesNumerous phagolysosomesStaphylococciGram-positive bacteriaNephritisUpdate on the Native Kidney Biopsy: Core Curriculum 2019
Luciano RL, Moeckel GW. Update on the Native Kidney Biopsy: Core Curriculum 2019. American Journal Of Kidney Diseases 2019, 73: 404-415. PMID: 30661724, DOI: 10.1053/j.ajkd.2018.10.011.BooksConceptsKidney biopsyKidney diseaseCore Curriculum 2019Arteriovenous fistula formationNative kidney biopsiesPercutaneous kidney biopsyKidney biopsy procedureReal-time ultrasoundGross hematuriaPerinephric hematomaFistula formationPotential complicationsLower riskBiopsyBiopsy procedureGenetic testingSpecific procedural aspectsGold standardDiseaseComplicationsSimple light microscopyPreferred methodLight microscopyTomographic imagingHematuria
2018
Reliability of deceased‐donor procurement kidney biopsy images uploaded in United Network for Organ Sharing
Mansour SG, Hall IE, Reese PP, Jia Y, Thiessen‐Philbrook H, Moeckel G, Weng FL, Revelo MP, Khalighi MA, Trivedi A, Doshi MD, Schröppel B, Parikh CR. Reliability of deceased‐donor procurement kidney biopsy images uploaded in United Network for Organ Sharing. Clinical Transplantation 2018, 32: e13441. PMID: 30387908, PMCID: PMC6317379, DOI: 10.1111/ctr.13441.Peer-Reviewed Original ResearchTREX1 Mutation Causing Autosomal Dominant Thrombotic Microangiopathy and CKD—A Novel Presentation
Gulati A, Bale AE, Dykas DJ, Bia MJ, Danovitch GM, Moeckel GW, Somlo S, Dahl NK. TREX1 Mutation Causing Autosomal Dominant Thrombotic Microangiopathy and CKD—A Novel Presentation. American Journal Of Kidney Diseases 2018, 72: 895-899. PMID: 29941221, DOI: 10.1053/j.ajkd.2018.05.006.Peer-Reviewed Original ResearchConceptsRenal thrombotic microangiopathyThrombotic microangiopathyTREX1 mutationsRetinal microangiopathyChronic kidney diseaseRepair exonuclease 1Whole-exome sequencingSignificant brainSymptomatic brainTREX1 variantsKidney involvementClinical presentationKidney diseaseCerebral leukodystrophyComplement dysregulationMicroangiopathyClinical importanceDiverse causesComplement regulationNovel presentationSubstantial proportionBrainSignificant proportionGenetic determinantsCauseThe protective role of macrophage migration inhibitory factor in acute kidney injury after cardiac surgery
Stoppe C, Averdunk L, Goetzenich A, Soppert J, Marlier A, Kraemer S, Vieten J, Coburn M, Kowark A, Kim BS, Marx G, Rex S, Ochi A, Leng L, Moeckel G, Linkermann A, El Bounkari O, Zarbock A, Bernhagen J, Djudjaj S, Bucala R, Boor P. The protective role of macrophage migration inhibitory factor in acute kidney injury after cardiac surgery. Science Translational Medicine 2018, 10 PMID: 29769287, DOI: 10.1126/scitranslmed.aan4886.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAnimalsAntigens, Differentiation, B-LymphocyteAntioxidantsCardiac Surgical ProceduresCell DeathHistocompatibility Antigens Class IIHumansIncidenceInflammationKidneyLipid PeroxidationLipocalin-2Macrophage Migration-Inhibitory FactorsMice, Inbred C57BLOxidative StressProtective AgentsProtein DomainsRecombinant ProteinsReperfusion InjuryRhabdomyolysisConceptsMacrophage migration inhibitory factorAcute kidney injuryRecombinant macrophage migration inhibitory factorIschemia-reperfusion injuryCardiac surgeryMigration inhibitory factorTubular epithelial cellsKidney injuryHigher macrophage migration inhibitory factorIncidence of AKIPathogenesis of AKIUrinary Macrophage Migration Inhibitory FactorExperimental acute kidney injuryExperimental ischemia-reperfusion injuryInhibitory factorMyocardial ischemia-reperfusion injuryOxidative stressMIF serum concentrationsCardiac surgery patientsRenal tubular epithelial cellsConventional cardiac surgeryEpithelial cellsHours of reperfusionSetting of hypoxiaTubular cell injuryGranulomatosis With Polyangiitis in a Young Adult With Down Syndrome
Mensah KA, Pascha V, Moeckel G, Danve A. Granulomatosis With Polyangiitis in a Young Adult With Down Syndrome. JCR Journal Of Clinical Rheumatology 2018, 24: 153-156. PMID: 29200025, DOI: 10.1097/rhu.0000000000000633.Peer-Reviewed Original ResearchAcute Kidney InjuryAdultAntibodies, Antineutrophil CytoplasmicBiopsyBlood TransfusionDiagnosis, DifferentialDown SyndromeGlucocorticoidsGranulomatosis with PolyangiitisHemoptysisHumansImmunoglobulins, IntravenousImmunologic FactorsKidneyMalePatient Care ManagementPatient SelectionRespiration, ArtificialRespiratory InsufficiencyRituximabTomography, X-Ray ComputedTreatment OutcomeSemaphorin 7A in circulating regulatory T cells is increased in autosomal-dominant polycystic kidney disease and decreases with tolvaptan treatment
Lee Y, Blount KL, Dai F, Thompson S, Scher JK, Bitterman S, Droher M, Herzog EL, Moeckel G, Karihaloo A, Dahl NK. Semaphorin 7A in circulating regulatory T cells is increased in autosomal-dominant polycystic kidney disease and decreases with tolvaptan treatment. Clinical And Experimental Nephrology 2018, 22: 906-916. PMID: 29453607, DOI: 10.1007/s10157-018-1542-x.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsAutosomal dominant polycystic kidney diseaseEnd-stage renal diseaseRenal fibrosisSEMA7A expressionADPKD patientsTolvaptan treatmentPolycystic kidney diseaseKidney diseaseNumber of PBMCsExpression of SEMA7ASubsequent renal fibrosisMarkers of inflammationRegulatory T cellsADPKD kidneysBlood mononuclear cellsImmunomodulating proteinsRenal diseaseMononuclear cellsSmall kidneysKidney fibrosisLiver fibrosisRenal cystsSemaphorin 7AT cellsPathologic Perspectives on Acute Tubular Injury Assessment in the Kidney Biopsy
Moeckel GW. Pathologic Perspectives on Acute Tubular Injury Assessment in the Kidney Biopsy. Seminars In Nephrology 2018, 38: 21-30. PMID: 29291758, DOI: 10.1016/j.semnephrol.2017.09.003.Peer-Reviewed Original ResearchConceptsAcute tubular injuryKidney biopsy analysisRenal pathology laboratoryTissue injury markersClinical time courseCell injury pathwaysTime courseNephrologists' managementInjury markersTubular injuryTubular lesionsKidney biopsyPathophysiological mechanismsTreatment modalitiesPatient managementDrug choiceEtiologic mechanismsInjury pathwaysToxic injuryPathologic perspectiveToxic etiologyBiopsy samplesClinical practiceBiopsy analysisPathology practice
2017
Rapamycin treatment dose‐dependently improves the cystic kidney in a new ADPKD mouse model via the mTORC1 and cell‐cycle‐associated CDK1/cyclin axis
Li A, Fan S, Xu Y, Meng J, Shen X, Mao J, Zhang L, Zhang X, Moeckel G, Wu D, Wu G, Liang C. Rapamycin treatment dose‐dependently improves the cystic kidney in a new ADPKD mouse model via the mTORC1 and cell‐cycle‐associated CDK1/cyclin axis. Journal Of Cellular And Molecular Medicine 2017, 21: 1619-1635. PMID: 28244683, PMCID: PMC5543471, DOI: 10.1111/jcmm.13091.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticCDC2 Protein KinaseCell CycleCyclinsDose-Response Relationship, DrugFemaleFounder EffectGene Expression RegulationHumansIntegrasesKidneyMaleMiceMice, TransgenicMicrofilament ProteinsPolycystic Kidney, Autosomal DominantPromoter Regions, GeneticSignal TransductionSirolimusTOR Serine-Threonine KinasesTRPP Cation ChannelsConceptsAutosomal dominant polycystic kidney diseaseEnd-stage renal diseaseMouse modelCyclin-dependent kinase 1Kidney/body weight ratioPreclinical trialsVivo preclinical resultsBody weight ratioCre transgenic miceHigh-dose rapamycinStandardized animal modelHuman autosomal dominant polycystic kidney diseaseRapamycin (mTOR) inhibitor rapamycinDominant polycystic kidney diseaseMonths of ageOrthologous mouse modelConditional knockout miceDose-dependent mannerPolycystic kidney diseaseAberrant epithelial cell proliferationEpithelial cell proliferationNew molecular targetsADPKD therapyRenal functionADPKD mouse modelHistones and Neutrophil Extracellular Traps Enhance Tubular Necrosis and Remote Organ Injury in Ischemic AKI
Nakazawa D, Kumar SV, Marschner J, Desai J, Holderied A, Rath L, Kraft F, Lei Y, Fukasawa Y, Moeckel GW, Angelotti ML, Liapis H, Anders HJ. Histones and Neutrophil Extracellular Traps Enhance Tubular Necrosis and Remote Organ Injury in Ischemic AKI. Journal Of The American Society Of Nephrology 2017, 28: 1753-1768. PMID: 28073931, PMCID: PMC5461800, DOI: 10.1681/asn.2016080925.Peer-Reviewed Original ResearchConceptsNeutrophil extracellular trap formationExtracellular trap formationNeutrophil extracellular trapsTubular necrosisExtracellular trapsCell necrosisTubular epithelial cell deathTubular epithelial cell necrosisRemote organ dysfunctionRemote organ injuryRemote organ damageRenal ischemic injuryTubular cell necrosisIschemia-reperfusion injuryRemote tissue injuryAdditive protective effectEpithelial cell necrosisTUNEL-positive cellsEpithelial cell deathNovel molecular targetsTrap formationIschemic AKISevere AKIKidney injuryMultiorgan dysfunction
2016
Eculizumab Therapy for Chronic Antibody‐Mediated Injury in Kidney Transplant Recipients: A Pilot Randomized Controlled Trial
Kulkarni S, Kirkiles‐Smith N, Deng YH, Formica RN, Moeckel G, Broecker V, Bow L, Tomlin R, Pober JS. Eculizumab Therapy for Chronic Antibody‐Mediated Injury in Kidney Transplant Recipients: A Pilot Randomized Controlled Trial. American Journal Of Transplantation 2016, 17: 682-691. PMID: 27501352, DOI: 10.1111/ajt.14001.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntibodies, Monoclonal, HumanizedChronic DiseaseComplement C5Complement Inactivating AgentsEarly Intervention, EducationalFemaleFollow-Up StudiesGlomerular Filtration RateGraft RejectionGraft SurvivalHumansIsoantibodiesKidney Failure, ChronicKidney Function TestsKidney TransplantationLiving DonorsMaleMiddle AgedPilot ProjectsPrognosisRisk FactorsTissue DonorsTransplant RecipientsYoung AdultConceptsDe novo donor-specific antibodiesComplement inhibitionTreatment groupsNovo donor-specific antibodiesAntibody-Mediated InjuryC1q-positive patientsDonor-specific antibodiesKidney transplant recipientsPrimary end pointEndothelial cell injuryMo of observationEculizumab therapyEculizumab treatmentHumoral injuryTransplant recipientsKidney transplantRenal functionKidney functionChronic settingEGFR trajectoriesTreatment periodCell injuryPatientsEnd pointPercentage change