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, 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 analysisIdentification 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
Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury
Wen Y, Su E, Xu L, Menez S, Moledina D, Obeid W, Palevsky P, Mansour S, Devarajan P, Cantley L, Cahan P, Parikh C, Project K, Injury T. Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury. Science Translational Medicine 2023, 15: eade7287. PMID: 38091407, PMCID: PMC11405121, DOI: 10.1126/scitranslmed.ade7287.Peer-Reviewed Original ResearchThe 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 EGFIdentification 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 insultThe Lymphatic System in Kidney Disease
Baker M, Cantley L. The Lymphatic System in Kidney Disease. Kidney360 2023, 4: e841-e850. PMID: 37019177, PMCID: PMC10371377, DOI: 10.34067/kid.0000000000000120.Peer-Reviewed Original ResearchConceptsKidney diseaseLymphatic systemSetting of AKIKidney allograft rejectionNormal kidney functionImmune response modulationAllograft rejectionLymph nodesInflammatory infiltrateKidney functionImmune cellsTissue edemaNovel therapiesImmune surveillanceNumerous disease statesSystemic circulationFluid removalKidney tissueResident cellsTherapeutic potentialSurveillance cellsAKIDisease statesKidneyResponse modulationThe ion transporter Na+-K+-ATPase enables pathological B cell survival in the kidney microenvironment of lupus nephritis
Chernova I, Song W, Steach H, Hafez O, Al Souz J, Chen P, Chandra N, Cantley L, Veselits M, Clark M, Craft J. The ion transporter Na+-K+-ATPase enables pathological B cell survival in the kidney microenvironment of lupus nephritis. Science Advances 2023, 9: eadf8156. PMID: 36724234, PMCID: PMC9891690, DOI: 10.1126/sciadv.adf8156.Peer-Reviewed Original ResearchConceptsB cellsAutoimmune diseasesAmelioration of proteinuriaLupus nephritis biopsiesB cell infiltrationSodium-potassium adenosine triphosphataseB cell survivalPotassium adenosine triphosphataseLupus nephritisCell infiltrationKidney microenvironmentTissue injuryTherapeutic targetPharmacological inhibitionElevated sodium concentrationLupusHostile microenvironmentHigh expressionKidneySodium concentrationGenetic knockoutCell survivalDiseaseCellsAdenosine triphosphatase
2022
Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease
Liu J, Nair V, Zhao Y, Chang D, Limonte C, Bansal N, Fermin D, Eichinger F, Tanner E, Bellovich K, Steigerwalt S, Bhat Z, Hawkins J, Subramanian L, Rosas S, Sedor J, Vasquez M, Waikar S, Bitzer M, Pennathur S, Brosius F, De Boer I, Chen M, Kretzler M, Ju W, Group F, Knight R, Lecker S, Stillman I, Bogen S, Amodu A, Ilori T, Maikhor S, Schmidt I, Beck L, Henderson J, Onul I, Verma A, Waikar S, McMahon G, Valerius M, Waikar S, Weins A, Colona M, Greka A, Hacohen N, Hoover P, Marshall J, Aulisio M, Chen Y, Janowczyk A, Jayapandian C, Viswanathan V, Bush W, Crawford D, Madabhushi A, Bush L, Cooperman L, Gonzalez-Vicente A, Herlitz L, Jolly S, Nguyen J, O’toole J, Palmer E, Poggio E, Sedor J, Sendrey D, Spates-Harden K, Taliercio J, Bjornstad P, Pyle L, Vinovskis C, Appelbaum P, Barasch J, Bomback A, Canetta P, D’Agati V, Kiryluk K, Kudose S, Mehl K, Shang N, Balderes O, Bansal S, Alexandrov T, Rennke H, El-Achkar T, Barwinska D, Bledsoe S, Borner K, Bueckle A, Cheng Y, Dagher P, Dunn K, Eadon M, Ferkowicz M, Herr B, Kelly K, Ferreira R, Quardokus E, Record E, Rivera M, Su J, Sutton T, Williams J, Winfree S, Menez S, Parikh C, Rosenberg A, Corona-Villalobos C, Wen Y, Johansen C, Rosas S, Roy N, Sun J, Williams M, Azeloglu E, Hansen J, He C, Iyengar R, Xiong Y, Prasad P, Srivastava A, Madhavan S, Parikh S, Rovin B, Shapiro J, Anderton C, Lukowski J, Pasa-Tolic L, Velickovic D, Oliver G, Ardayfio J, Bebiak J, Brown K, Campbell T, Campbell C, Hayashi L, Jefferson N, Roberts G, Saul J, Shpigel A, Stutzke C, Koewler R, Pinkeney R, Sealfon R, Troyanskaya O, Wong A, Tuttle K, Pollack A, Goltsev Y, Lucarelli N, Sarder P, Lake B, Zhang K, Boada P, Laszik Z, Nolan G, Anjani K, Sarwal M, Mukatash T, Sigdel T, Alloway R, Burg A, Lee P, Rike A, Shi T, Woodle E, Balis U, Blanc V, Conser N, Eddy S, Frey R, He Y, Hodgin J, Kretzler M, Lienczewski C, Luo J, Mariani L, Menon R, Otto E, Schaub J, Steck B, Elder M, Gilliam M, Hall D, Murugan R, Palevsky P, Randhawa P, Rosengart M, Tublin M, Vita T, Kellum J, Winters J, Alpers C, Berglund A, Blank K, Carson J, Daniel S, De Boer I, Dighe A, Dowd F, Grewenow S, Himmelfarb J, Hoofnagle A, Limonte C, McClelland R, Mooney S, Rezaei K, Shankland S, Snyder J, Wang R, Wilcox A, Williams K, Park C, Bansal S, Montellano R, Pamreddy A, Sharma K, Venkatachalam M, Ye H, Zhang G, Hedayati S, Kermani A, Lee S, Lu C, Miller R, Moe O, Patel J, Pillai A, Sambandam K, Torrealba J, Toto R, Vazquez M, Wang N, Wen N, Zhang D, Park H, Caprioli R, Patterson N, Sharman K, Spraggins J, Van de Plas R, Basta J, Diettman S, Gaut J, Jain S, Rauchman M, Vijayan A, Cantley L, Kakade V, Moledina D, Shaw M, Ugwuowo U, Wilson F, Arora T, Bitzer M, Brosius F, Gadegbeku C, Gipson D, Hawkins J, Kretzler M, Lienczewski C, Pennathur S, Troost J, Gadegbeku C, Bellovich K, Bhat Z, Massengill S, Perumal K. Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease. Diabetes 2022, 71: 2664-2676. PMID: 36331122, PMCID: PMC9750948, DOI: 10.2337/db22-0169.Peer-Reviewed Original ResearchConceptsEnd-stage kidney diseaseDiabetic kidney diseaseKidney diseaseAngiopoietin-2ANGPT2 levelsChinese cohort studyChronic kidney diseaseGlomerular filtration rateCardiovascular Health StudyPlasma angiopoietin-2High receptor expressionStandard clinical parametersSignaling Pathway ActivationPathway scoresThree-marker panelKidney outcomesCohort studyComposite outcomeClinical parametersEndothelial biomarkersFiltration rateReceptor expressionPrognostic biomarkerClinical phenotypingHealth StudyAuthors' Reply: Most Arginase-1 Positive Cells Are Likely Injured S3 Proximal Tubular Cells Carrying Upregulated Phagocytotic Capacity rather than M2 Macrophages—Too Many To Be True
Shin N, Marlier A, Xu L, Doilicho N, Linberg D, Guo J, Cantley L. Authors' Reply: Most Arginase-1 Positive Cells Are Likely Injured S3 Proximal Tubular Cells Carrying Upregulated Phagocytotic Capacity rather than M2 Macrophages—Too Many To Be True. Journal Of The American Society Of Nephrology 2022, 33: 2124-2125. PMID: 36316094, PMCID: PMC9678031, DOI: 10.1681/asn.2022070836.Peer-Reviewed Original ResearchImmune-Mediated Tubule Atrophy Promotes AKI to CKD Transition
Xu L, Guo J, Moledina D, Cantley L. Immune-Mediated Tubule Atrophy Promotes AKI to CKD Transition. Journal Of The American Society Of Nephrology 2022, 33: 872-872. DOI: 10.1681/asn.20223311s1872b.Peer-Reviewed Original ResearchImmune-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 5Interferon activated gene 204 protects against bone loss in experimental periodontitis
Swanson KV, Girnary M, Alves T, Ting JP, Divaris K, Beck J, Pucinelli CM, da Silva RAB, Uyan D, Wilson JE, Seaman WT, Webster‐Cyriaque J, Vias N, Jiao Y, Cantley L, Marlier A, Arnold RR, Marchesan JT. Interferon activated gene 204 protects against bone loss in experimental periodontitis. Journal Of Periodontology 2022, 93: 1366-1377. PMID: 35404474, PMCID: PMC9489626, DOI: 10.1002/jper.21-0668.Peer-Reviewed Original ResearchConceptsBone lossHuman endothelial cellsOsteoclast numberPeriodontal pathogensRecent human genetic association studiesHigher alveolar bone lossEndothelial cellsPeriodontal disease biomarkersAlveolar bone lossNeutrophils/macrophagesInterferon gamma-inducible protein 16Inflammatory cell traffickingInducible protein 16Periodontitis developmentChemokine responsesExperimental periodontitisInflammatory infiltrationPeriodontal destructionMarrow sourcesGingival tissuesMelanoma 2Periodontal tissuesLigature modelChimeric miceAlveolar boneArginase-1 Is Required for Macrophage-Mediated Renal Tubule Regeneration
Shin NS, Marlier A, Xu L, Doilicho N, Linberg D, Guo J, Cantley LG. Arginase-1 Is Required for Macrophage-Mediated Renal Tubule Regeneration. Journal Of The American Society Of Nephrology 2022, 33: 1077-1086. PMID: 35577558, PMCID: PMC9161787, DOI: 10.1681/asn.2021121548.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryTubular cell proliferationArginase-1Contralateral nephrectomyRenal repairFl/Littermate controlsTubular cellsReceptor 1GM-CSFRenal tubular cell proliferationRenal tubule regenerationMacrophage scavenger receptor 1Mannose receptor 1Cell proliferative responsesCell proliferationScavenger receptor 1Coculture of macrophagesDead cell debrisKidney injuryKidney repairRenal responseProinflammatory activationTubule regenerationMouse survivalMortality 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 activationCharacterization of temporospatial distribution of renal tubular casts by nephron tracking after ischemia-reperfusion injury
Shin NS, Marlier A, Xu L, Lam T, Cantley LG, Guo JK. Characterization of temporospatial distribution of renal tubular casts by nephron tracking after ischemia-reperfusion injury. American Journal Of Physiology. Renal Physiology 2022, 322: f322-f334. PMID: 35100823, PMCID: PMC8897010, DOI: 10.1152/ajprenal.00284.2021.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryCast formationGlomerular filtration rateTubular cast formationUrine 24 hDetached epithelial cellsDead cell debrisRenal recoveryRenal functionFiltration rateS3 tubulesTubular castsTubular cellsTubular nucleiKidney sectionsOuter medullaTrypsin levelsEntire nephronRenal tubular castsFuture interventionsInjurySelective lossTubule segmentsEpithelial cellsKidney
2021
Using Imaging Mass Cytometry to Define Cell Identities and Interactions in Human Tissues
Kakade VR, Weiss M, Cantley LG. Using Imaging Mass Cytometry to Define Cell Identities and Interactions in Human Tissues. Frontiers In Physiology 2021, 12: 817181. PMID: 35002783, PMCID: PMC8727440, DOI: 10.3389/fphys.2021.817181.Peer-Reviewed Original ResearchSingle-cell sequencingComplex cellular microenvironmentHuman disease pathogenesisKidney cell typesCell identityHuman kidney samplesMultiplexed imaging techniquesMass cytometryCell sequencingCellular microenvironmentCell typesNovel insightsImaging Mass CytometryHuman tissuesDisease pathogenesisPathophysiological processesCellular dataAntibody validationProteomicsCytometryHuman kidneyIMC analysisSequencingKidney samplesPhenotypingDevelopment and external validation of a diagnostic model for biopsy-proven acute interstitial nephritis using electronic health record data
Moledina DG, Eadon MT, Calderon F, Yamamoto Y, Shaw M, Perazella MA, Simonov M, Luciano R, Schwantes-An TH, Moeckel G, Kashgarian M, Kuperman M, Obeid W, Cantley LG, Parikh CR, Wilson FP. Development and external validation of a diagnostic model for biopsy-proven acute interstitial nephritis using electronic health record data. Nephrology Dialysis Transplantation 2021, 37: 2214-2222. PMID: 34865148, PMCID: PMC9755995, DOI: 10.1093/ndt/gfab346.Peer-Reviewed Original ResearchConceptsAcute interstitial nephritisInterstitial nephritisUrine biomarkersBiopsy-proven acute interstitial nephritisElectronic health record dataExternal validation cohortTypical clinical featuresBlood urea nitrogenTumor necrosis factorCharacteristic curve analysisHealth record dataExternal validationElectronic health recordsAIN diagnosisModest AUCsSerum creatinineCreatinine ratioKidney biopsyClinical featuresValidation cohortNecrosis factorUnrecognized casesInterleukin-9PatientsUrea nitrogenCadherin-11, Sparc-related modular calcium binding protein-2, and Pigment epithelium-derived factor are promising non-invasive biomarkers of kidney fibrosis
Schmidt I, Colona M, Kestenbaum B, Alexopoulos L, Palsson R, Srivastava A, Liu J, Stillman I, Rennke H, Vaidya V, Wu H, Humphreys B, Waikar S, Knight R, Lecker S, Stillman I, Bogen S, Amodu A, Ilori T, Maikhor S, Schmidt I, Beck L, Henderson J, Onul I, Verma A, McMahon G, Valerius M, Waikar S, Weins A, Colona M, Greka A, Hacohen N, Hoover P, Marshall J, Aulisio M, Chen Y, Janowczyk A, Jayapandian C, Viswanathan V, Bush W, Crawford D, Madabhushi A, Bush L, Cooperman L, Gonzalez-Vicente A, Herlitz L, Jolly S, Nguyen J, O’toole J, Palmer E, Poggio E, Sedor J, Sendrey D, Spates-Harden K, Taliercio J, Bjornstad P, Pyle L, Vinovskis C, Appelbaum P, Balderes O, Barasch J, Bomback A, Canetta P, D’Agati V, Kiryluk K, Kudose S, Mehl K, Shang N, Bansal S, Alexandrov T, Rennke H, El-Achkar T, Barwinska D, Bledso S, Borner K, Bueckle A, Cheng Y, Dagher P, Dunn K, Eadon M, Ferkowicz M, Herr B, Kelly K, Ferreira R, Quardokus E, Record E, Rivera M, Su J, Sutton T, Williams J, Winfree S, Jain Y, Menez S, Parikh C, Rosenberg A, Corona-Villalobos C, Wen Y, Johansen C, Rosas S, Roy N, Sun J, Williams M, Azeloglu E, Hansen J, He C, Iyengar R, Xiong Y, Prasad P, Srivastava A, Madhavan S, Parikh S, Rovin B, Shapiro J, Anderton C, Lukowski J, Pasa-Tolic L, Velickovic D, Oliver G, Ardayfio J, Bebiak J, Brown K, Campbell T, Campbell C, Hayashi L, Jefferson N, Roberts G, Saul J, Shpigel A, Stutzke C, Koewler R, Pinkeney R, Sealfon R, Troyanskaya O, Wong A, Tuttle K, Pollack A, Goltsev Y, Ginley B, Lucarelli N, Lutnick B, Sarder P, Lake B, Zhang K, Boada P, Laszik Z, Nolan G, Anjani K, Sarwal M, Mukatash T, Sigdel T, Alloway R, Burg A, Lee P, Rike A, Shi T, Woodle E, Ascani H, Balis U, Blanc V, Conser N, Eddy S, Frey R, He Y, Hodgin J, Kretzler M, Lienczewski C, Luo J, Mariani L, Menon R, Otto E, Schaub J, Steck B, Elder M, Gilliam M, Hall D, Murugan R, Palevsky P, Randhawa P, Rosengart M, Tublin M, Vita T, Winters J, Kellum J, Alpers C, Berglund A, Berry B, Blank K, Carson J, Daniel S, De Boer I, Dighe A, Dowd F, Grewenow S, Himmelfarb J, Hoofnagle A, Limonte C, McClelland R, Mooney S, Rezaei K, Shankland S, Snyder J, Wang R, Wilcox A, Williams K, Park C, Bansal S, Montellano R, Pamreddy A, Sharma K, Venkatachalam M, Ye H, Zhang G, Basit M, Hedayati S, Kermani A, Lee S, Lu C, Miller R, Moe O, Patel J, Pillai A, Sambandam K, Torrealba J, Toto R, Vazquez M, Wang N, Wen N, Zhang D, Park H, Caprioli R, Patterson N, Sharman K, Spraggins J, Van de Plas R, Basta J, Diettman S, Gaut J, Jain S, Rauchman M, Vijayan A, Cantley L, Kakade V, Moledina D, Shaw M, Ugwuowo U, Wilson F, Arora T. Cadherin-11, Sparc-related modular calcium binding protein-2, and Pigment epithelium-derived factor are promising non-invasive biomarkers of kidney fibrosis. Kidney International 2021, 100: 672-683. PMID: 34051265, PMCID: PMC8384690, DOI: 10.1016/j.kint.2021.04.037.Peer-Reviewed Original ResearchConceptsPigment epithelium-derived factorBoston Kidney Biopsy CohortEnd-stage kidney diseaseChronic kidney diseaseModular calcium binding protein-2Seattle Kidney StudyKidney fibrosisKidney diseaseEpithelium-derived factorNon-invasive biomarkersBiopsy cohortTubular atrophyInterstitial fibrosisKidney StudyBinding protein 2Cox proportional hazards regression modelHuman chronic kidney diseaseProportional hazards regression modelsUrine biomarker levelsCohort of patientsHazards regression modelsPromising non-invasive biomarkerIndependent prospective cohortsAssociation of biomarkersNon-invasive assessment