Featured Publications
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 differencesPatientsUrine 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 diseaseDevelopment 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 nitrogenMortality 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 activationUrine interleukin-9 and tumor necrosis factor-α for prognosis of human acute interstitial nephritis
Moledina DG, Wilson FP, Kukova L, Obeid W, Luciano R, Kuperman M, Moeckel GW, Kashgarian M, Perazella MA, Cantley LG, Parikh CR. Urine interleukin-9 and tumor necrosis factor-α for prognosis of human acute interstitial nephritis. Nephrology Dialysis Transplantation 2020, 36: 1851-1858. PMID: 33125471, PMCID: PMC8476079, DOI: 10.1093/ndt/gfaa169.Peer-Reviewed Original ResearchConceptsAcute interstitial nephritisTumor necrosis factorCorticosteroid useIL-9Interstitial nephritisNecrosis factorAcute kidney injuryIL-9 levelsGlomerular filtration rateSubset of patientsCohort of participantsImmunosuppressive therapyTubulointerstitial infiltratesKidney injuryMedian eGFRKidney functionUrine biomarkersInterstitial fibrosisFiltration rateHistological featuresClinical trialsInterleukin-9PatientsEGFRComplete dataThe Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study
Moledina DG, Simonov M, Yamamoto Y, Alausa J, Arora T, Biswas A, Cantley LG, Ghazi L, Greenberg JH, Hinchcliff M, Huang C, Mansour SG, Martin M, Peixoto A, Schulz W, Subair L, Testani JM, Ugwuowo U, Young P, Wilson FP. The Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study. American Journal Of Kidney Diseases 2021, 77: 490-499.e1. PMID: 33422598, PMCID: PMC7791318, DOI: 10.1053/j.ajkd.2020.12.007.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAgedCohort StudiesCOVID-19C-Reactive ProteinCreatinineDiureticsFemaleHospital MortalityHumansIntensive Care UnitsLength of StayMaleMiddle AgedProportional Hazards ModelsRenal DialysisRenal Insufficiency, ChronicRespiration, ArtificialRisk FactorsSARS-CoV-2Severity of Illness IndexUnited StatesVasoconstrictor AgentsConceptsAcute kidney injurySARS-CoV-2Cohort studyRisk factorsCOVID-19Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testingTime-updated Cox proportional hazards modelsDialysis-requiring acute kidney injuryYale New Haven Health SystemHigher inflammatory marker levelsMore acute kidney injuryCox proportional hazards modelMulticenter cohort studyHigh rateInflammatory marker levelsTraditional risk factorsProportional hazards modelCoronavirus disease 2019KDIGO criteriaNephrotoxin exposureKidney injuryInjury independentUnivariable analysisNasopharyngeal samplesMarker levelsUrine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis
Melchinger H, Calderon-Gutierrez F, Obeid W, Xu L, Shaw MM, Luciano RL, Kuperman M, Moeckel GW, Kashgarian M, Wilson FP, Parikh CR, Moledina DG. Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis. Clinical Journal Of The American Society Of Nephrology 2022, 17: 1284-1292. PMID: 35948365, PMCID: PMC9625093, DOI: 10.2215/cjn.04360422.Peer-Reviewed Original ResearchConceptsInterstitial fibrosis/tubular atrophyUrine uromodulinTubular atrophyThick ascending limbUrine albuminSerum creatinineKidney biopsyTubulointerstitial fibrosisMultivariable linear regression modelsTime of biopsyKidney's thick ascending limbAcademic medical centerHuman kidney biopsiesKidney tubulointerstitial fibrosisTubular healthMultivariable analysisHistologic featuresHistologic findingsHistologic changesKidney fibrosisIndependent associationFibrotic modelMultivariable modelMedical CenterMurine model
2024
The development of lateral flow devices for urinary biomarkers to assess kidney health
D Souza S, Obeid W, Hernandez J, Hu D, Wen Y, Moledina D, Albert A, Gregg A, Wheeler A, Philbrook H, Parikh C. The development of lateral flow devices for urinary biomarkers to assess kidney health. Scientific Reports 2024, 14: 8516. PMID: 38609491, PMCID: PMC11014899, DOI: 10.1038/s41598-024-59104-5.Peer-Reviewed Original ResearchConceptsLateral flow deviceInterleukin-9Development of lateral flow devicesUrinary biomarkersDetection antibody concentrationSerum creatinine levelsKidney healthPaired antibodiesEnzyme Linked Immunosorbent AssayCreatinine levelsKidney injuryKidney functionOsteopontinImmunosorbent assayAntibody concentrationsMeasured biomarkersKidneyReal-time changesBiomarkersCOVID-19−Associated Acute Kidney Injury and Longitudinal Kidney Outcomes
Aklilu A, Kumar S, Nugent J, Yamamoto Y, Coronel-Moreno C, Kadhim B, Faulkner S, O’Connor K, Yasmin F, Greenberg J, Moledina D, Testani J, Wilson F. COVID-19−Associated Acute Kidney Injury and Longitudinal Kidney Outcomes. JAMA Internal Medicine 2024, 184: 414-423. PMID: 38407862, PMCID: PMC10897825, DOI: 10.1001/jamainternmed.2023.8225.Peer-Reviewed Original ResearchCOVID-19-associated acute kidney injuryCOVID-19-associated AKIAcute kidney injuryMulticenter cohort studyKidney function declineKidney functionKidney injuryCohort studyKidney outcomes of patientsIncidence of acute kidney injuryLong-term kidney outcomesHistorical cohort of patientsMultivariate time-to-event analysesPositive influenza ALongitudinal multicenter cohort studyWorsening kidney functionOutcomes of patientsAdverse kidney eventsCohort of patientsComposite of mortalityMarkers of illness severityAdult hospitalized patientsBaseline comorbidity scoreTime-to-event analysisFunctional declineUrinary Plasminogen as a Marker of Disease Progression in Human Glomerular Disease
de Cos M, Mosoyan G, Chauhan K, Troost J, Wong J, Lefferts S, Morgan P, Meliambro K, Egerman M, Ray J, Parker T, Levine D, Seshan S, Bardash Y, Horowitz B, Kent C, Shaw M, Perlman A, Moledina D, Coca S, Campbell K. Urinary Plasminogen as a Marker of Disease Progression in Human Glomerular Disease. American Journal Of Kidney Diseases 2024, 84: 205-214.e1. PMID: 38452919, PMCID: PMC11260534, DOI: 10.1053/j.ajkd.2024.01.520.Peer-Reviewed Original ResearchAssociated with end-stage kidney diseaseEnd-stage kidney diseaseUrinary plasmin(ogenGlomerular diseaseGlomerular disordersBiopsy-proven glomerular diseaseVariable clinical courseDevelopment of novel therapiesCohort of patientsRestricted to patientsElectro-chemiluminescence immunoassayHuman glomerular diseasesClinical courseUrinary markersUrine creatinineAbstractText Label="RATIONALENovel therapiesPrognostic decision makingCox regressionWhite patientsDisease progressionKidney diseasePatientsPodocyte injuryCohortRationale 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 agentToxic Nephropathies of the Tubulointerstitium: Core Curriculum 2024
Krishnan N, Moledina D, Perazella M. Toxic Nephropathies of the Tubulointerstitium: Core Curriculum 2024. American Journal Of Kidney Diseases 2024, 83: 659-676. PMID: 38243994, DOI: 10.1053/j.ajkd.2023.09.017.Peer-Reviewed Original ResearchRenal injurySeverity of renal injuryToxic nephropathyTubulointerstitial renal injuryIrreversible renal injuryToxin-induced renal injuryImmune response genesNephrotoxic riskClinical presentationTubulointerstitial injuryRenal functionClinical manifestationsPatient characteristicsTubular secretionGlomerular filtrationComorbid conditionsMetabolic handlingDrug metabolismExcretory pathwayInjuryTransport defectAdverse effectsTubulointerstitiumNephropathyExogenous toxins
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 ResearchAnalysis 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, DOI: 10.1126/scitranslmed.ade7287.Peer-Reviewed Original ResearchUrinary Biomarkers and Kidney Injury in VA NEPHRON-D: Phenotyping Acute Kidney Injury in Clinical Trials
Kiernan E, Hu D, Philbrook H, Ix J, Bonventre J, Coca S, Moledina D, Fried L, Shlipak M, Parikh C. Urinary Biomarkers and Kidney Injury in VA NEPHRON-D: Phenotyping Acute Kidney Injury in Clinical Trials. American Journal Of Kidney Diseases 2023, 83: 151-161. PMID: 37726051, PMCID: PMC10841767, DOI: 10.1053/j.ajkd.2023.07.012.Peer-Reviewed Original ResearchAcute kidney injuryKidney injuryClinical trialsSerum creatinineUrinary biomarkersAKI eventsVA NEPHRONCombination armUrine biomarkersDiabetic chronic kidney disease patientsChronic Kidney Disease trialChronic kidney disease patientsAldosterone system blockadeCombination therapy armKidney Disease TrialRAAS inhibitor therapySafety end pointCombination therapy groupKidney disease patientsBiomarkers of injuryAKI incidenceKidney outcomesMonotherapy armRAAS blockadeRAASi therapyOutcomes Associated with Sodium-Glucose Cotransporter-2 Inhibitor Use in Acute Heart Failure Hospitalizations Complicated by AKI
Aklilu A, Kumar S, Yamamoto Y, Moledina D, Sinha F, Testani J, Wilson F. Outcomes Associated with Sodium-Glucose Cotransporter-2 Inhibitor Use in Acute Heart Failure Hospitalizations Complicated by AKI. Kidney360 2023, 4: 1371-1381. PMID: 37644648, PMCID: PMC10615381, DOI: 10.34067/kid.0000000000000250.Peer-Reviewed Original ResearchConceptsAcute kidney injuryHeart failure hospitalizationSodium-glucose cotransporter-2 inhibitor useSodium-glucose cotransporter 2 inhibitorsAcute heart failure hospitalizationCotransporter 2 inhibitorsCox regression analysisRenal recoveryFailure hospitalizationAKI diagnosisKidney injuryInhibitor useLower riskStage 5 chronic kidney diseaseTime-varying Cox regression analysisKidney Disease Improving Global OutcomesInverse probability-weighted analysisMulticenter retrospective cohort studyMultivariable Cox regression analysisStage 5 CKDAcute heart failureRetrospective cohort studyChronic kidney diseaseKidney function recoveryGlomerular filtration rateThe 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 EGFComparative evaluation of glomerular morphometric techniques reveals differential technical artifacts between focal segmental glomerulosclerosis and normal glomeruli
Reghuvaran A, Lin Q, Basgen J, Banu K, Shi H, Vashist A, Pell J, Perinchery S, He J, Moledina D, Wilson F, Menon M. Comparative evaluation of glomerular morphometric techniques reveals differential technical artifacts between focal segmental glomerulosclerosis and normal glomeruli. Physiological Reports 2023, 11: e15688. PMID: 37423891, PMCID: PMC10329935, DOI: 10.14814/phy2.15688.Peer-Reviewed Original ResearchEvaluation of Plasma Biomarkers to Predict Major Adverse Kidney Events in Hospitalized Patients With COVID-19
Menez S, Coca S, Moledina D, Wen Y, Chan L, Thiessen-Philbrook H, Obeid W, Garibaldi B, Azeloglu E, Ugwuowo U, Sperati C, Arend L, Rosenberg A, Kaushal M, Jain S, Wilson F, Parikh C, Consortium T, Deng J, Atta M, Bagnasco S, Ko A, Iwasaki A, Farhadian S, Nelson A, Casanovas-Massana A, White E, Schulz W, Coppi A, Young P, Nunez A, Shepard D, Matos I, Strong Y, Anastasio K, Brower K, Kuang M, Chiorazzi M, Bermejo S, Vijayakumar P, Geng B, Fournier J, Minasyan M, Muenker M, Moore A, Nadkarni G. Evaluation of Plasma Biomarkers to Predict Major Adverse Kidney Events in Hospitalized Patients With COVID-19. American Journal Of Kidney Diseases 2023, 82: 322-332.e1. PMID: 37263570, PMCID: PMC10229201, DOI: 10.1053/j.ajkd.2023.03.010.Peer-Reviewed Original ResearchConceptsSoluble tumor necrosis factor receptor 1Major adverse kidney eventsAdverse kidney eventsAdverse kidney outcomesAcute kidney injuryKidney eventsTumor necrosis factor receptor 1Necrosis factor receptor 1Plasma biomarkersKidney outcomesC-indexFactor receptor 1Hospitalized patientsCOVID-19KDIGO stage 3 acute kidney injuryDialysis-requiring acute kidney injuryStage 3 acute kidney injuryLong-term adverse health outcomesReceptor 1Long-term kidney dysfunctionAvailable blood samplesIdentification of patientsProportional hazards regressionAdverse health outcomesCOVID-19 hospitalizationA randomized clinical trial assessing the effect of automated medication-targeted alerts on acute kidney injury outcomes
Wilson F, Yamamoto Y, Martin M, Coronel-Moreno C, Li F, Cheng C, Aklilu A, Ghazi L, Greenberg J, Latham S, Melchinger H, Mansour S, Moledina D, Parikh C, Partridge C, Testani J, Ugwuowo U. A randomized clinical trial assessing the effect of automated medication-targeted alerts on acute kidney injury outcomes. Nature Communications 2023, 14: 2826. PMID: 37198160, PMCID: PMC10192367, DOI: 10.1038/s41467-023-38532-3.Peer-Reviewed Original ResearchConceptsAcute kidney injuryUsual care groupKidney injuryCare groupAcute Kidney Injury OutcomesAlert groupNon-steroidal anti-inflammatory drugsComposite of progressionHours of randomizationMedications of interestAldosterone system inhibitorsClasses of medicationsProton pump inhibitorsRandomized clinical trialsAnti-inflammatory drugsClinical decision support systemNephrotoxic medicationsHospitalized adultsDiscontinuation ratesCertain medicationsPrimary outcomeSubstantial morbiditySystem inhibitorsPump inhibitorsParallel group