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
Hypergranulotic 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 diseaseTelavancin-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 determinantsCauseGranulomatosis 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 cells
2017
Loss of the podocyte glucocorticoid receptor exacerbates proteinuria after injury
Zhou H, Tian X, Tufro A, Moeckel G, Ishibe S, Goodwin J. Loss of the podocyte glucocorticoid receptor exacerbates proteinuria after injury. Scientific Reports 2017, 7: 9833. PMID: 28852159, PMCID: PMC5575043, DOI: 10.1038/s41598-017-10490-z.Peer-Reviewed Original ResearchConceptsKnockout miceGlucocorticoid receptorNephrotic syndromeSimilar renal functionMainstay of therapyReceptor knockout miceTreatment of proteinuriaFoot process effacementMechanism of actionImmunomodulatory therapyRenal functionGlomerular injuryProtein excretionKO miceCommon disorderNephrotoxic serumPodocyte injuryPodocyte-specific deletionMouse modelSlit diaphragm proteinsWild-type podocytesProcess effacementProteinuriaUnstimulated conditionsKnockout animalsMIF-2/D-DT enhances proximal tubular cell regeneration through SLPI- and ATF4-dependent mechanisms
Ochi A, Chen D, Schulte W, Leng L, Moeckel N, Piecychna M, Averdunk L, Stoppe C, Bucala R, Moeckel G. MIF-2/D-DT enhances proximal tubular cell regeneration through SLPI- and ATF4-dependent mechanisms. American Journal Of Physiology. Renal Physiology 2017, 313: f767-f780. PMID: 28539339, PMCID: PMC6148305, DOI: 10.1152/ajprenal.00683.2016.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 4Acute Kidney InjuryAnimalsAntigens, Differentiation, B-LymphocyteApoptosisAutophagyCell HypoxiaCell LineCell ProliferationCyclin D1Disease Models, AnimalEukaryotic Initiation Factor-2FemaleGenetic Predisposition to DiseaseHistocompatibility Antigens Class IIIntramolecular OxidoreductasesKidney Tubules, ProximalMacrophage Migration-Inhibitory FactorsMaleMice, Inbred C57BLMice, KnockoutPhenotypeRegenerationReperfusion InjurySecretory Leukocyte Peptidase InhibitorSignal TransductionTime FactorsTransfectionConceptsMacrophage migration inhibitory factorSecretory leukocyte proteinase inhibitorTubular cell regenerationProximal tubular cellsD-DTCell regenerationTubular cellsIschemic acute kidney injuryIschemia-reperfusion injury modelWild-type control miceMouse proximal tubular cellsAcute kidney injuryIschemia-reperfusion injuryRenal proximal tubular cellsMigration inhibitory factorIntegrated stress responseATF4-dependent mechanismCyclin D1 expressionEukaryotic initiation factorKidney injuryTubular injuryControl miceChemokine receptorsInjury modelInflammatory contextRapamycin 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
2015
Antiphospholipid Antibody Syndrome
Rudich DS, Yun SH, Liebling A, Silbert JE, Moeckel GW, Lesser RL. Antiphospholipid Antibody Syndrome. Journal Of Neuro-Ophthalmology 2015, 35: 396-399. PMID: 26049680, DOI: 10.1097/wno.0000000000000277.Peer-Reviewed Original ResearchA Nodular Foreign Body Reaction in a Dialysis Patient Receiving Long-term Treatment With Lanthanum Carbonate
Valika AK, Jain D, Jaffe PE, Moeckel G, Brewster UC. A Nodular Foreign Body Reaction in a Dialysis Patient Receiving Long-term Treatment With Lanthanum Carbonate. American Journal Of Kidney Diseases 2015, 67: 128-132. PMID: 26385816, DOI: 10.1053/j.ajkd.2015.07.033.Peer-Reviewed Case Reports and Technical NotesConceptsEnd-stage renal diseaseLanthanum carbonate treatmentUpper gastrointestinal bleedSimilar pathologic findingsLong-term treatmentCollections of histiocytesForeign body reactionGastrointestinal bleedGastrointestinal bleedingUpper endoscopyDialysis patientsHIV infectionRenal diseaseComorbid conditionsPathologic findingsAdverse reactionsHyperechoic materialEndoscopic ultrasoundHyperplastic epitheliumPhosphate bindersGiant cellsLanthanum carbonateGranular cytoplasmic materialPatientsBody reactionComparison of amyloid deposition in human kidney biopsies as predictor of poor patient outcome
Castano E, Palmer MB, Vigneault C, Luciano R, Wong S, Moeckel G. Comparison of amyloid deposition in human kidney biopsies as predictor of poor patient outcome. BMC Nephrology 2015, 16: 64. PMID: 25924613, PMCID: PMC4424547, DOI: 10.1186/s12882-015-0046-0.Peer-Reviewed Original ResearchConceptsEnd-stage renal diseaseAmyloid depositionPatient outcomesAmyloid depositsBiopsy-proven renal amyloidosisHistological localizationHigher serum creatinineInterstitial inflammatory infiltrateStage renal diseaseUrine protein levelsGlomerular amyloid depositionGlomerular amyloid depositsPoor patient outcomesGlomerular capillary loopsHuman kidney biopsiesDifferent study groupsStudent's t-testGlomerular amyloidosisOverall survivalSerum creatinineVascular amyloidosisKidney biopsyRenal diseaseInflammatory infiltrateClinical parameters
2014
Chemokine receptor Cxcr4 contributes to kidney fibrosis via multiple effectors
Yuan A, Lee Y, Choi U, Moeckel G, Karihaloo A. Chemokine receptor Cxcr4 contributes to kidney fibrosis via multiple effectors. American Journal Of Physiology. Renal Physiology 2014, 308: f459-f472. PMID: 25537742, PMCID: PMC4346747, DOI: 10.1152/ajprenal.00146.2014.Peer-Reviewed Original ResearchConceptsUnilateral ureteral obstructionCXCR4 expressionKidney fibrosisChemokine receptorsFibrotic responseSmooth muscle actin levelsG protein-coupled chemokine receptorsGrowth factorChronic kidney inflammationProgressive tissue injuryChronic kidney diseaseHigh CXCR4 expressionTGF-β1 levelsEffector cell typesProgression of fibrosisScarring/fibrosisFinal common pathwayPlatelet-derived growth factorRenal injuryKidney inflammationObstructed kidneysBone morphogenetic protein-7Renal fibrosisUreteral obstructionKidney diseaseGM-CSF Promotes Macrophage Alternative Activation after Renal Ischemia/Reperfusion Injury
Huen SC, Huynh L, Marlier A, Lee Y, Moeckel GW, Cantley LG. GM-CSF Promotes Macrophage Alternative Activation after Renal Ischemia/Reperfusion Injury. Journal Of The American Society Of Nephrology 2014, 26: 1334-1345. PMID: 25388222, PMCID: PMC4446881, DOI: 10.1681/asn.2014060612.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAnalysis of VarianceAnimalsBlotting, WesternCell ProliferationCells, CulturedDisease Models, AnimalGene Expression RegulationGranulocyte-Macrophage Colony-Stimulating FactorImmunohistochemistryKidney Tubules, ProximalMacrophage ActivationMaleMiceMice, Inbred C57BLMultivariate AnalysisPhenotypeRandom AllocationReal-Time Polymerase Chain ReactionReperfusion InjurySignal TransductionUp-RegulationConceptsIschemia/reperfusion injuryMacrophage alternative activationBone marrow-derived macrophagesAlternative activationMarrow-derived macrophagesTubular cellsGM-CSFReperfusion injuryReparative phenotypeTubular proliferationKidney ischemia/reperfusion injuryRenal ischemia/reperfusion injuryMouse proximal tubule cellsInitial kidney damageRepair phaseProximal tubule cellsTubular factorsIschemic injuryKidney damageProinflammatory macrophagesRenal repairMacrophage activationTubule cellsPharmacologic inhibitionMacrophages