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 differencesPatients
2019
Secretory Leukocyte Protease Inhibitor (SLPI)—A Novel Predictive Biomarker of Acute Kidney Injury after Cardiac Surgery: A Prospective Observational Study
Averdunk L, Fitzner C, Levkovich T, Leaf DE, Sobotta M, Vieten J, Ochi A, Moeckel G, Marx G, Stoppe C. Secretory Leukocyte Protease Inhibitor (SLPI)—A Novel Predictive Biomarker of Acute Kidney Injury after Cardiac Surgery: A Prospective Observational Study. Journal Of Clinical Medicine 2019, 8: 1931. PMID: 31717603, PMCID: PMC6912354, DOI: 10.3390/jcm8111931.Peer-Reviewed Original ResearchSecretory leukocyte protease inhibitorAcute kidney injuryCardiac surgeryLeukocyte protease inhibitorKidney injuryEarly diagnosisBiomarkers of AKIPathogenesis of AKINon-AKI patientsProspective observational studyNovel predictive biomarkerStandard clinical predictorsNovel candidate biomarkersProtease inhibitorsAKI patientsFrequent complicationSerum creatinineClinical predictorsUrine outputPoor outcomeUrinary levelsPredictive biomarkersObservational studyIndependent cohortSurgeryRegulated 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 bacteriaNephritisChapter 83 Adaptive Immunity and Critical Illness
Schulte W, Maerz L, Moeckel G, Bucala R. Chapter 83 Adaptive Immunity and Critical Illness. 2019, 483-487. DOI: 10.1016/b978-0-323-44942-7.00083-2.Peer-Reviewed Original ResearchAcute kidney injuryCritical illnessEnd-stage renal diseaseChronic kidney diseaseChallenging clinical conditionIschemia-reperfusion injuryComplex disease processAdaptive immune systemAKI pathophysiologyKidney injuryHospitalized patientsRenal diseaseKidney diseaseInflammatory processCommon causeClinical conditionsAdaptive immunityLong-term consequencesDisease processImmune systemSubsequent treatmentInjuryIllnessDiseaseCurrent knowledge
2018
The 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 injury
2017
Severe Orthostatic Hypotension Complicating Multiple Myeloma
Sury K, Mutter M, Moeckel G, Perazella M. Severe Orthostatic Hypotension Complicating Multiple Myeloma. Journal Of Onco-Nephrology 2017, 1: e8-e12. DOI: 10.5301/jo-n.5000029.Peer-Reviewed Original ResearchRenal replacement therapySevere hemodynamic instabilityVascular amyloidosisMultiple myelomaOrthostatic hypotensionHemodynamic instabilityReplacement therapyContinuous veno-venous hemodialysisSevere orthostatic hypotensionAcute kidney injuryMaximal medical therapyFatal cardiac arrestGlomerular amyloidosisKidney injuryUrinary findingsPersistent symptomsKidney biopsyMedical therapyKidney functionCardiac arrestMultiple fallsRenal amyloidosisTreatment challengesClinical aspectsAmyloidosisA case of severe nephrotoxicity associated with long-term dietary supplement use
Koraishy FM, Moeckel GW, Geller DS. A case of severe nephrotoxicity associated with long-term dietary supplement use. Clinical Nephrology 2017, 5: 42-47. PMID: 28766491, PMCID: PMC5642467, DOI: 10.5414/cncs109180.BooksDietary supplement useDietary supplementsSupplement useNew-onset renal failureNon-steroidal anti-inflammatory drugsAcute interstitial nephritisCourse of prednisoneAcute kidney injuryAcute tubular necrosisNephrotic range proteinuriaAnti-inflammatory drugsCherry extractKidney injuryRenal failureSerum creatinineTubular necrosisInterstitial nephritisRenal biopsyKidney diseaseSevere nephrotoxicityCyclooxygenase inhibitorSide effectsProteinuriaDaily intakeHealth benefitsRenal recovery following orthotopic liver transplant after prolonged kidney injury: Perspectives on diagnosing hepatorenal syndrome and determining which patients should undergo simultaneous liver kidney transplantation
Card M, Moeckel G, Turner J. Renal recovery following orthotopic liver transplant after prolonged kidney injury: Perspectives on diagnosing hepatorenal syndrome and determining which patients should undergo simultaneous liver kidney transplantation. Journal Of Renal And Hepatic Disorders 2017, 1: 25-28. DOI: 10.15586/jrenhep.2017.20.Peer-Reviewed Original ResearchOrthotopic liver transplantHepatorenal syndromeRenal recoveryLiver transplantSimultaneous liver-kidney transplantSimultaneous liver-kidney transplantationLiver-kidney transplantSignificant renal recoveryLiver-kidney transplantationMonths of dialysisImmunoglobulin A (IgA) nephropathyCurrent diagnostic criteriaKidney injuryKidney transplantationRenal failureA NephropathyIgA depositsCase seriesGlomerular injuryGlomerular lesionsDiagnostic criteriaPatientsDiagnostic approachTransplantCirrhosisMIF-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 contextHistones 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
2014
Bile Acid Nephropathy in a Bodybuilder Abusing an Anabolic Androgenic Steroid
Luciano RL, Castano E, Moeckel G, Perazella MA. Bile Acid Nephropathy in a Bodybuilder Abusing an Anabolic Androgenic Steroid. American Journal Of Kidney Diseases 2014, 64: 473-476. PMID: 24953892, DOI: 10.1053/j.ajkd.2014.05.010.Peer-Reviewed Case Reports and Technical NotesConceptsAcute kidney injurySevere cholestatic liver diseaseCholestatic liver diseaseLiver diseaseAcute tubular injury/necrosisCases of AKIEnd-stage liver diseaseBile acid injurySevere obstructive jaundiceAcute tubular injuryAnabolic androgenic steroidsAnabolic-androgenic steroid useCholemic nephrosisHepatorenal syndromeKidney injuryTubular injuryObstructive jaundiceHemodynamic changesTubular toxicitySteroid useAcid injuryHepatic diseaseTubular cellsHeterogeneous lesionsNephropathyRenalase Prevents AKI Independent of Amine Oxidase Activity
Wang L, Velazquez H, Moeckel G, Chang J, Ham A, Lee HT, Safirstein R, Desir GV. Renalase Prevents AKI Independent of Amine Oxidase Activity. Journal Of The American Society Of Nephrology 2014, 25: 1226-1235. PMID: 24511138, PMCID: PMC4033373, DOI: 10.1681/asn.2013060665.Peer-Reviewed Original ResearchConceptsIschemic injuryCatecholamine levelsRecombinant renalaseAmine oxidase activityHuman proximal tubular cellsCisplatin-induced AKITreatment of AKIWild-type miceHK-2 cellsProximal tubular cellsOxidase activityKidney injuryRenal injuryC-Jun N-terminal kinaseExtracellular signal-regulated kinaseP38 mitogen-activated protein kinaseToxic injuryRenalase proteinTubular cellsSignal-regulated kinaseIntracellular signaling cascadesRenalaseInjuryMitogen-activated protein kinaseN-terminal kinase
2013
Met Activation Is Required for Early Cytoprotection after Ischemic Kidney Injury
Mason S, Hader C, Marlier A, Moeckel G, Cantley LG. Met Activation Is Required for Early Cytoprotection after Ischemic Kidney Injury. Journal Of The American Society Of Nephrology 2013, 25: 329-337. PMID: 24136921, PMCID: PMC3904569, DOI: 10.1681/asn.2013050473.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAnimalsApoptosisBcl-Associated Death ProteinGene Knockdown TechniquesKidneyKidney Tubules, ProximalMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutOrgan SpecificityPhosphatidylinositol 3-KinasesPhosphorylationProtein Processing, Post-TranslationalProto-Oncogene Proteins c-aktReceptor Protein-Tyrosine KinasesReperfusion InjuryRibosomal Protein S6 Kinases, 70-kDaSignal TransductionConceptsIschemia/reperfusionKidney injuryIschemic injuryProximal tubulesInitial tubular injuryMET receptor expressionProximal tubule responseTubular cell survivalIschemic kidney injuryProximal tubule epithelial cellsRenal proximal tubule epithelial cellsTubular cell proliferationTubular cell apoptosisPI3K/Akt activationProapoptotic factor BadTubule epithelial cellsCell survivalTubule responseSerum creatinineTubular injuryKidney repairLiver abnormalitiesReceptor expressionInjuryMET activationWarfarin-related nephropathy in a patient with mild IgA nephropathy on dabigatran and aspirin
Moeckel GW, Luciano RL, Brewster UC. Warfarin-related nephropathy in a patient with mild IgA nephropathy on dabigatran and aspirin. Clinical Kidney Journal 2013, 6: 507-509. PMID: 26120444, PMCID: PMC4438392, DOI: 10.1093/ckj/sft076.Peer-Reviewed Case Reports and Technical NotesAcute kidney injuryTubular injuryIgA nephropathyMild IgA nephropathyAcute tubular injuryLong-term anticoagulationDirect thrombin inhibitorKidney injurySevere hematuriaRenal biopsyGlomerular pathologyDabigatranPatientsThrombin inhibitorsNephropathyInjuryWarfarinAnticoagulationHematuriaAspirinBiopsyPathologyAldosterone stimulates fibronectin synthesis in renal fibroblasts through mineralocorticoid receptor-dependent and independent mechanisms
Chen D, Chen Z, Park C, Centrella M, McCarthy T, Chen L, Al-Omari A, Moeckel GW. Aldosterone stimulates fibronectin synthesis in renal fibroblasts through mineralocorticoid receptor-dependent and independent mechanisms. Gene 2013, 531: 23-30. PMID: 23994292, DOI: 10.1016/j.gene.2013.08.047.Peer-Reviewed Original ResearchConceptsProgression of fibrosisFibronectin synthesisChronic kidney diseaseC-Jun NH2-terminal protein kinaseMineralocorticoid hormone aldosteroneKidney fibroblast cell lineTranscription factor c-JunExtracellular signal-regulated kinaseReceptor-dependent activationSignal-regulated kinaseDependent signaling pathwaysKidney injuryInterstitial fibrosisKidney diseaseMineralocorticoid receptorHormone aldosteroneAldosteroneRenal fibroblastsAnimal modelsProtein kinaseFibroblast cell lineFibronectin expressionKidneyFibrosisSubsequent phosphorylationAcute kidney injury in a patient with sarcoidosis: hypercalciuria and hypercalcemia leading to calcium phosphate deposition.
Manjunath V, Moeckel G, Dahl NK. Acute kidney injury in a patient with sarcoidosis: hypercalciuria and hypercalcemia leading to calcium phosphate deposition. Clinical Nephrology 2013, 80: 151-5. PMID: 23845267, DOI: 10.5414/cn107258.Peer-Reviewed Original ResearchConceptsAcute kidney injuryAcute tubular necrosisKidney injuryOH vitamin D levelsVitamin D levelsCalcium oxalate nephrolithiasisRenal functionTubular necrosisKidney biopsyKidney functionCalcium phosphate depositionD levelsGiant cell formationOxalate nephrolithiasisSarcoidosisRandall's plaqueHypercalcemiaHypercalciuriaPatientsInjuryPhosphate depositionPlaquesCell formationCalcium phosphate crystalsDifferent mechanismsMacrophage-specific deletion of transforming growth factor-β1 does not prevent renal fibrosis after severe ischemia-reperfusion or obstructive injury
Huen SC, Moeckel GW, Cantley LG. Macrophage-specific deletion of transforming growth factor-β1 does not prevent renal fibrosis after severe ischemia-reperfusion or obstructive injury. American Journal Of Physiology. Renal Physiology 2013, 305: f477-f484. PMID: 23761668, PMCID: PMC3891258, DOI: 10.1152/ajprenal.00624.2012.Peer-Reviewed Original ResearchConceptsGrowth factor-β1Kidney injuryKidney diseaseRenal fibrosisTGF-β1Factor-β1Renal ischemia-reperfusion injuryChronic kidney diseaseIschemia-reperfusion injuryProgressive renal fibrosisMacrophage-specific deletionInnate immune responseMyeloid lineage cellsPersistence of macrophagesLater time pointsTubulointerstitial fibrosisFibrosis markersInterstitial fibrosisMacrophage infiltrationEffective therapyInjury modelObstructive injuryImmune responseTissue scarringFibrosisBabesiosis-Induced Acute Kidney Injury With Prominent Urinary Macrophages
Luciano RL, Moeckel G, Palmer M, Perazella MA. Babesiosis-Induced Acute Kidney Injury With Prominent Urinary Macrophages. American Journal Of Kidney Diseases 2013, 62: 801-805. PMID: 23643302, DOI: 10.1053/j.ajkd.2013.02.376.Peer-Reviewed Case Reports and Technical NotesConceptsAcute kidney injuryAcute tubular injuryKidney injuryTubular injuryDialysis-requiring acute kidney injuryAcute interstitial nephritisMultiorgan system failureSubsequent kidney biopsySevere symptomatic diseaseUrinary macrophagesUrinary findingsInterstitial nephritisKidney biopsySymptomatic diseaseMassive hemolysisSevere babesiosisVolume depletionCommon causeProfound hemolysisErythrocyte fragmentsUrine sedimentInjuryLarge macrophagesPigment toxicityUnique findingRenalase protects against cisplatin acute kidney injury in mice
Desir G, Wang L, Velazquez H, Moeckel G, Safirstein R. Renalase protects against cisplatin acute kidney injury in mice. The FASEB Journal 2013, 27: 910.7-910.7. DOI: 10.1096/fasebj.27.1_supplement.910.7.Peer-Reviewed Original ResearchCisplatin acute kidney injuryAcute kidney injuryRenalase expressionKidney injuryCisplatin-induced acute kidney injuryIschemic acute kidney injuryRenal injury scoreUseful therapeutic optionHK-2 cellsImportant clinical syndromeRenalase deficiencyTubular necrosisPro-survival signalsTherapeutic optionsClinical syndromeInjury scorePlasma creatinineKO miceEffective therapyRenalaseBCL2 expressionMarked reductionProtective actionCaspase-3Injury