2024
VCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition
Melchinger I, Guo K, Li X, Guo J, Cantley L, Xu L. VCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition. American Journal Of Physiology. Renal Physiology 2024, 327: f610-f622. PMID: 39116349, PMCID: PMC11483080, DOI: 10.1152/ajprenal.00076.2024.Peer-Reviewed Original ResearchAcute kidney injuryChronic kidney diseaseVCAM-1 expressionProximal tubule cellsVCAM-1Tubule cellsKidney Precision Medicine ProjectProinflammatory cytokinesAcute kidney injury to chronic kidney diseaseModel of chronic kidney diseaseExpression of vascular cell adhesion protein 1Cell adhesion pathwaysInflammatory response to injuryInjured proximal tubule cellsVascular cell adhesion protein 1Mouse model of chronic kidney diseaseRisk of progressionChronic kidney disease transitionIncreased immune cell adhesionVCAM-1-positive cellsOverexpression of VCAM-1Inhibition of NF-kB signalingActivation of NF-kBImmune cell adhesionSingle-cell transcriptome analysis
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 differencesPatientsLongitudinal biomarkers and kidney disease progression after acute kidney injury
Wen Y, Xu L, Melchinger I, Thiessen-Philbrook H, Moledina D, Coca S, Hsu C, Go A, Liu K, Siew E, Ikizler T, Chinchilli V, Kaufman J, Kimmel P, Himmelfarb J, Cantley L, Parikh C, Consortium T. Longitudinal biomarkers and kidney disease progression after acute kidney injury. JCI Insight 2023, 8: e167731. PMID: 36951957, PMCID: PMC10243801, DOI: 10.1172/jci.insight.167731.Peer-Reviewed Original ResearchConceptsAcute kidney injuryIschemic reperfusion injuryKidney disease progressionKidney injuryTubular healthDisease progressionChronic kidney disease (CKD) incidenceCox proportional hazards regressionMurine acute kidney injuryKidney disease incidenceUrine KIM-1Proportional hazards regressionCKD progressionCKD transitionUrine uromodulinIncident CKDComposite outcomeKidney atrophyProspective cohortReperfusion injuryHazards regressionKIM-1Prognostic valueMCP-1Initial insult
2022
Immune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition
Xu L, Guo J, Moledina DG, Cantley LG. Immune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition. Nature Communications 2022, 13: 4892. PMID: 35986026, PMCID: PMC9391331, DOI: 10.1038/s41467-022-32634-0.Peer-Reviewed Original ResearchConceptsAcute kidney injuryKidney injuryT cellsChronic kidney disease transitionIschemia-reperfusion kidney injuryKidney disease transitionChronic kidney diseaseDepletion of neutrophilsGlomerular filtration rateT cell recruitmentTubular cell lossMacrophage persistenceProinflammatory neutrophilsTubule damageKidney atrophyContralateral kidneyNeutrophil numbersContralateral nephrectomyKidney diseaseTubule atrophyFiltration rateCell recruitmentMore macrophagesDay 14Day 5Mortality after acute kidney injury and acute interstitial nephritis in patients prescribed immune checkpoint inhibitor therapy
Baker ML, Yamamoto Y, Perazella MA, Dizman N, Shirali AC, Hafez N, Weinstein J, Simonov M, Testani JM, Kluger HM, Cantley LG, Parikh CR, Wilson FP, Moledina DG. Mortality after acute kidney injury and acute interstitial nephritis in patients prescribed immune checkpoint inhibitor therapy. Journal For ImmunoTherapy Of Cancer 2022, 10: e004421. PMID: 35354588, PMCID: PMC8968986, DOI: 10.1136/jitc-2021-004421.Peer-Reviewed Original ResearchConceptsAcute interstitial nephritisAcute kidney injuryImmune checkpoint inhibitor therapyCheckpoint inhibitor therapyICI therapyKidney injuryInhibitor therapyInterstitial nephritisTime-varying Cox proportional hazards modelsHigher peak serum creatinineSevere acute kidney injuryCancer typesCox proportional hazards modelAssociations of biopsyBaseline laboratory valuesObservational cohort studyPeak serum creatinineFavorable treatment responseProportional hazards modelAKI patientsTherapy initiationCohort studySerum creatinineUnivariable analysisImmune activation
2015
The Role of p204 in Kidney Injury
Marlier A, Huen S, Lengyel P, Cantley L. The Role of p204 in Kidney Injury. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.807.1.Peer-Reviewed Original ResearchAcute kidney injuryIschemia-reperfusion injuryRenal ischemia-reperfusion injuryChronic kidney diseaseKidney injuryPeak serum creatinine levelClassical inflammatory stimuliSerum creatinine levelsTubular cell necrosisCD45-positive cellsWhole-body knockoutAKI biomarkersCreatinine levelsKidney diseaseCHI3L1 expressionKidney ischemiaKidney fibrosisInflammasome activationInflammatory stimuliReparative phasePositive cellsTherapeutic targetBone marrowWT controlsCell necrosis