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
The ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events
Menez S, Wen Y, Xu L, Moledina D, Thiessen-Philbrook H, Hu D, Obeid W, Bhatraju P, Ikizler T, Siew E, Chinchilli V, Garg A, Go A, Liu K, Kaufman J, Kimmel P, Himmelfarb J, Coca S, Cantley L, Parikh C. The ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events. Kidney International 2023, 104: 1194-1205. PMID: 37652206, PMCID: PMC10840723, DOI: 10.1016/j.kint.2023.08.007.Peer-Reviewed Original ResearchConceptsMajor adverse kidney eventsUEGF/CrUrinary epidermal growth factorAdverse kidney eventsChronic kidney diseaseEpidermal growth factorKidney eventsKidney failureEGF expressionUrinary EGF/CrAcute Kidney Injury studyGrowth factorIschemia-reperfusion injuryProportional hazards regressionTubular healthKidney atrophyObservational cohortHospitalized participantsTubular functionClinical findingsHazards regressionKidney diseaseClinical variablesProgressive atrophyUrinary EGF
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 5Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation
Guo X, Xu L, Velazquez H, Chen TM, Williams RM, Heller DA, Burtness B, Safirstein R, Desir GV. Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation. Journal Of The American Society Of Nephrology 2022, 33: 342-356. PMID: 34921111, PMCID: PMC8819981, DOI: 10.1681/asn.2021040439.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntineoplastic AgentsCell LineCisplatinCreatinineDisease Models, AnimalGene ExpressionGlomerular Filtration RateHepatitis A Virus Cellular Receptor 1HumansKidneyMiceMice, Inbred C57BLMice, KnockoutMonoamine OxidaseNanocapsulesPeptidesRenal Insufficiency, ChronicConceptsRenal proximal tubulesSingle-cell RNA sequencing analysisMesoscale nanoparticlesFirst doseCisplatin chemotherapyProximal tubulesAgonist peptideInduced Chronic Kidney DiseaseGenetic deletionNeck squamous cell carcinomaRNA sequencing analysisCisplatin-induced AKIKidney-targeted deliveryChronic kidney diseaseDevelopment of CKDSquamous cell carcinomaAdministration of cisplatinPlasma renalaseAdvanced headCell carcinomaInflammatory cytokinesKidney diseasePlasma creatinineSystemic administrationRegulated necrosis
2021
Biomarkers of inflammation and repair in kidney disease progression
Puthumana J, Thiessen-Philbrook H, Xu L, Coca SG, Garg AX, Himmelfarb J, Bhatraju PK, Ikizler T, Siew E, Ware LB, Liu KD, Go AS, Kaufman JS, Kimmel PL, Chinchilli VM, Cantley L, Parikh CR. Biomarkers of inflammation and repair in kidney disease progression. Journal Of Clinical Investigation 2021, 131 PMID: 33290282, PMCID: PMC7843225, DOI: 10.1172/jci139927.Peer-Reviewed Original ResearchConceptsKidney disease progressionComposite kidney outcomeChronic kidney diseaseDisease progressionEGFR declineKidney outcomesRenal atrophyMouse modelMonocyte chemoattractant protein-1CHI3L1 mRNA expressionComposite renal outcomeGreater eGFR declineIntroductionAcute kidney injuryProspective cohort studyGlomerular filtration rateBiomarkers of inflammationProgressive renal fibrosisYKL-40 levelsChemoattractant protein-1Traditional clinical variablesLong-term progressionLoop of HenleMultimarker scoreRenal outcomesKidney injury