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 Research
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 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 insult
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 StudyInterferon 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 bone
2021
Development 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
2019
Urine 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 disease
2015
Development of a Targeted Urine Proteome Assay for kidney diseases
Cantley LG, Colangelo CM, Stone KL, Chung L, Belcher J, Abbott T, Cantley JL, Williams KR, Parikh CR. Development of a Targeted Urine Proteome Assay for kidney diseases. Proteomics Clinical Applications 2015, 10: 58-74. PMID: 26220717, PMCID: PMC5003777, DOI: 10.1002/prca.201500020.Peer-Reviewed Original ResearchConceptsKidney diseaseUrinary proteinGraft functionImmediate graft functionDelayed graft functionKidney transplant patientsMultiple kidney diseasesTransplant patientsKidney transplantClinical relevancePotential biomarkersUrine proteomeDiseaseAvailable biofluidBiomarkersPatientsProtein biomarkersAssaysSingle assayProteome changesHuman urineQuantifiable proteinsTransplantProteinPeptides
2013
The Terminator mouse is a diphtheria toxin–receptor knock-in mouse strain for rapid and efficient enrichment of desired cell lineages
Guo JK, Shi H, Koraishy F, Marlier A, Ding Z, Shan A, Cantley LG. The Terminator mouse is a diphtheria toxin–receptor knock-in mouse strain for rapid and efficient enrichment of desired cell lineages. Kidney International 2013, 84: 1041-1046. PMID: 23739236, PMCID: PMC3775868, DOI: 10.1038/ki.2013.202.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersBlotting, WesternCell LineageCell SeparationCell SurvivalDiphtheria ToxinGenotypeHeparin-binding EGF-like Growth FactorImmunohistochemistryIntegrasesIntercellular Signaling Peptides and ProteinsKidney Tubules, ProximalMiceMice, Inbred C57BLMice, TransgenicPhenotypePodocytesPrimary Cell CultureRNA, UntranslatedTime FactorsConceptsDiphtheria toxin treatmentToxin treatmentPrimary culturesDiphtheria toxin receptor expressionDiphtheria toxin receptorCell typesProximal tubule cellsPodocin-cre miceToxin exposureTubule cellsMiceMouse strainsWestern blottingToxin receptorKidney cellsSpecific cell typesMarker proteinsCell lineagesCellsTreatmentChitinase-Like Protein Brp-39/YKL-40 Modulates the Renal Response to Ischemic Injury and Predicts Delayed Allograft Function
Schmidt IM, Hall IE, Kale S, Lee S, He CH, Lee Y, Chupp GL, Moeckel GW, Lee CG, Elias JA, Parikh CR, Cantley LG. Chitinase-Like Protein Brp-39/YKL-40 Modulates the Renal Response to Ischemic Injury and Predicts Delayed Allograft Function. Journal Of The American Society Of Nephrology 2013, 24: 309-319. PMID: 23291472, PMCID: PMC3559482, DOI: 10.1681/asn.2012060579.Peer-Reviewed Original ResearchMeSH KeywordsAdipokinesAnimalsApoptosisBiomarkersCells, CulturedChitinase-3-Like Protein 1Delayed Graft FunctionDisease Models, AnimalEpithelial CellsGlycoproteinsHumansKidneyKidney TransplantationLectinsMacrophagesMaleMiceMice, Inbred C57BLPhosphatidylinositol 3-KinasesPredictive Value of TestsProto-Oncogene Proteins c-aktReperfusion InjurySignal TransductionTransplantation, HomologousConceptsBRP-39/YKLGraft functionKidney injuryYKL-40Reparative responseDeceased donor kidney transplantationKidney ischemia/reperfusionHours of transplantImmediate graft functionDelayed graft functionTubular cell deathIschemia/reperfusionDegree of injuryAllograft functionCell apoptotic deathKidney hypoperfusionKidney transplantationSystemic hypotensionRenal failureIschemic injuryRenal ischemiaRenal responseUrinary levelsBRP-39Activation of Akt