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 ResearchRationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis
Barsotti G, Luciano R, Kumar A, Meliambro K, Kakade V, Tokita J, Naik A, Fu J, Peck E, Pell J, Reghuvaran A, Tanvir E, Patel P, Zhang W, Li F, Moeckel G, Perincheri S, Cantley L, Moledina D, Wilson F, He J, Menon M. Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis. Kidney International Reports 2024, 9: 1354-1368. PMID: 38707807, PMCID: PMC11068976, DOI: 10.1016/j.ekir.2024.02.006.Peer-Reviewed Original ResearchMinimal change diseaseRandomized controlled trialsSafety of metforminDouble-blindPodocyte injuryAdjunctive therapyPlacebo-controlled randomized controlled trialsPhase III studyPhase II trialPrimary glomerular diseaseFocal segmental glomerulosclerosisEffect of metforminPhase IIPlacebo-controlledPreclinical dataNovel urineChange diseaseTissue markersRandomized trialsSegmental glomerulosclerosisGlomerular diseaseMechanistic biomarkersObservational studyFSGSInexpensive agent
2023
APOBEC-1 deletion enhances cisplatin-induced acute kidney injury
Guo X, Blanc V, Davidson N, Velazquez H, Chen T, Moledina D, Moeckel G, Safirstein R, Desir G. APOBEC-1 deletion enhances cisplatin-induced acute kidney injury. Scientific Reports 2023, 13: 22255. PMID: 38097707, PMCID: PMC10721635, DOI: 10.1038/s41598-023-49575-3.Peer-Reviewed Original ResearchThrombotic Microangiopathy and Acute Tubular Injury After Diethylene Glycol Ingestion: A Kidney Biopsy Teaching Case
Malvar G, Gunasekaran D, Mehr N, Ishibe S, Moeckel G. Thrombotic Microangiopathy and Acute Tubular Injury After Diethylene Glycol Ingestion: A Kidney Biopsy Teaching Case. Kidney Medicine 2023, 6: 100758. PMID: 38304581, PMCID: PMC10831151, DOI: 10.1016/j.xkme.2023.100758.Peer-Reviewed Original ResearchAcute tubular injuryThrombotic microangiopathyTubular injuryEndothelial injuryPossible life-threatening complicationsDirect toxic injuryIncidence of AKIInitial gastrointestinal symptomsLife-threatening complicationsTypical clinical courseDiethylene glycol poisoningPeripheral sensorimotor neuropathyHigh mortality rateDiethylene glycol ingestionGastrointestinal symptomsClinical courseKidney biopsyGlycol ingestionSensorimotor neuropathyGlycol poisoningPathological lesionsToxic injuryGenetic predispositionUnusual caseMortality rateA Vexing Case
Dave D, Malvar G, Moeckel G, Shirali A. A Vexing Case. Journal Of The American Society Of Nephrology 2023, 34: 249-250. DOI: 10.1681/asn.20233411s1249d.Peer-Reviewed Original ResearchThrombotic Microangiopathy from Chafing Fuel Intoxication
Mehr N, Malvar G, Gunasekaran D, Ishibe S, Moeckel G. Thrombotic Microangiopathy from Chafing Fuel Intoxication. Journal Of The American Society Of Nephrology 2023, 34: 466-466. DOI: 10.1681/asn.20233411s1466d.Peer-Reviewed Original ResearchIdentification 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 impactComplicationsApplication of digital pathology and machine learning in the liver, kidney and lung diseases
Wu B, Moeckel G. Application of digital pathology and machine learning in the liver, kidney and lung diseases. Journal Of Pathology Informatics 2023, 14: 100184. PMID: 36714454, PMCID: PMC9874068, DOI: 10.1016/j.jpi.2022.100184.Peer-Reviewed Original ResearchWhole slide imagingArtificial intelligenceDigital pathologyAI technologyNeural networkIntegration of AIImplementation of AIDifferent AI technologiesTime-consuming taskDeep learningMachine learningSlide imagesImage patternsRapid developmentImage analysisNetworkLearningTechnologyRecent yearsIntelligenceMachineApplicationsTaskImagesVision
2022
Apobec-1 Limits Cisplatin and Ischemia-Reperfusion-Induced AKI
Guo X, Xu L, Velazquez H, Chen T, Blanc V, Davidson N, Moeckel G, Safirstein R, Desir G. Apobec-1 Limits Cisplatin and Ischemia-Reperfusion-Induced AKI. Journal Of The American Society Of Nephrology 2022, 33: 359-360. DOI: 10.1681/asn.20223311s1359e.Peer-Reviewed Original ResearchRenalase Protects Renal Injury by Maintaining Mitochondrial Dynamic Homeostasis
Guo X, Chen R, Chen T, Moeckel G, Safirstein R, Jonas E, Desir G. Renalase Protects Renal Injury by Maintaining Mitochondrial Dynamic Homeostasis. Journal Of The American Society Of Nephrology 2022, 33: 359-359. DOI: 10.1681/asn.20223311s1359d.Peer-Reviewed Original Research
2020
Kidney tissue hypoxia dictates T cell–mediated injury in murine lupus nephritis
Chen PM, Wilson PC, Shyer JA, Veselits M, Steach HR, Cui C, Moeckel G, Clark MR, Craft J. Kidney tissue hypoxia dictates T cell–mediated injury in murine lupus nephritis. Science Translational Medicine 2020, 12 PMID: 32269165, PMCID: PMC8055156, DOI: 10.1126/scitranslmed.aay1620.Peer-Reviewed Original ResearchConceptsHypoxia-inducible factor-1Lupus nephritisT cellsTissue hypoxiaT-cell-mediated injuryCell-mediated injuryHIF-1 blockadeKidney tissue hypoxiaSystemic lupus erythematosusHuman lupus nephritisMurine lupus nephritisRenal injuryAutoimmune injuryLupus erythematosusAutoimmune diseasesImmune cellsRenal tissueMurine modelTissue damageMore hypoxicNephritisInjuryLow oxygen tensionOxygen tensionFactor 1SUN-389 Collagenofibrotic glomerulopathy in kidney transplant recipient: A first report
Abu-Alfa A, Moeckel G, Kfrouy H, Jdiaa S. SUN-389 Collagenofibrotic glomerulopathy in kidney transplant recipient: A first report. Kidney International Reports 2020, 5: s359-s360. DOI: 10.1016/j.ekir.2020.02.929.Peer-Reviewed Case Reports and Technical NotesPolycystin 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 lesionsSecretory 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 cohortSurgeryHypergranulotic 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 administration