2024
Plasma proteomics of acute tubular injury
Schmidt I, Surapaneni A, Zhao R, Upadhyay D, Yeo W, Schlosser P, Huynh C, Srivastava A, Palsson R, Kim T, Stillman I, Barwinska D, Barasch J, Eadon M, El-Achkar T, Henderson J, Moledina D, Rosas S, Claudel S, Verma A, Wen Y, Lindenmayer M, Huber T, Parikh S, Shapiro J, Rovin B, Stanaway I, Sathe N, Bhatraju P, Coresh J, Rhee E, Grams M, Waikar S. Plasma proteomics of acute tubular injury. Nature Communications 2024, 15: 7368. PMID: 39191768, PMCID: PMC11349760, DOI: 10.1038/s41467-024-51304-x.Peer-Reviewed Original ResearchConceptsAcute tubular injuryAcute kidney injuryPathway analysisOrganelle stress responsesSingle-cell RNA sequencingKidney Precision Medicine ProjectKidney diseaseSOMAscan proteomics platformProgression to kidney failureRNA sequencingBiological pathwaysGene expressionStress responseNon-invasive biomarkersProteomics platformMannose receptor 1Kidney injuryTubular injuryImmune regulationReceptor 1Macrophage mannose receptor 1Host responseBiomarker proteinsPrecision Medicine ProjectKidney failureThe 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 changesBiomarkers
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 ResearchOutcomes 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 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 differencesPatientsEvaluation 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 groupJoint Modeling of Clinical and Biomarker Data in Acute Kidney Injury Defines Unique Subphenotypes with Differing Outcomes
Vasquez-Rios G, Oh W, Lee S, Bhatraju P, Mansour S, Moledina D, Gulamali F, Siew E, Garg A, Sarder P, Chinchilli V, Kaufman J, Hsu C, Liu K, Kimmel P, Go A, Wurfel M, Himmelfarb J, Parikh C, Coca S, Nadkarni G. Joint Modeling of Clinical and Biomarker Data in Acute Kidney Injury Defines Unique Subphenotypes with Differing Outcomes. Clinical Journal Of The American Society Of Nephrology 2023, 18: 716-726. PMID: 36975209, PMCID: PMC10278836, DOI: 10.2215/cjn.0000000000000156.Peer-Reviewed Original ResearchConceptsSubphenotype 2Pro-brain natriuretic peptideNeutrophil gelatinase-associated lipocalinCox proportional hazards modelAKI stage 1AKI stage 2AKI stage 3Three-fold riskAcute kidney injuryTroponin T levelsGelatinase-associated lipocalinBiomarkers of inflammationKidney injury moleculeLongitudinal clinical outcomesTumor necrosis factor receptor 1Proportional hazards modelNecrosis factor receptor 1Factor receptor 1AKI subphenotypesCardiorenal eventsSepsis-AKISubphenotype 1Cardiovascular eventsKidney injuryHazard ratio
2022
Pre-operative kidney biomarkers and risks for death, cardiovascular and chronic kidney disease events after cardiac surgery: the TRIBE-AKI study
Vasquez-Rios G, Moledina D, Jia Y, McArthur E, Mansour S, Thiessen-Philbrook H, Shlipak M, Koyner J, Garg A, Parikh C, Coca S. Pre-operative kidney biomarkers and risks for death, cardiovascular and chronic kidney disease events after cardiac surgery: the TRIBE-AKI study. Journal Of Cardiothoracic Surgery 2022, 17: 338. PMID: 36567329, PMCID: PMC9790121, DOI: 10.1186/s13019-022-02066-4.Peer-Reviewed Original ResearchConceptsKidney injury molecule-1Cardiovascular eventsCardiac surgeryCKD eventsCohort studyPlasma kidney injury molecule-1Chronic kidney disease (CKD) incidenceKidney disease incidenceKidney function dataPre-operative concentrationsInjury molecule-1Evaluation of patientsHigh-risk adultsLong-term outcomesHigh-risk individualsTumor necrosis factor receptorNecrosis factor receptorKidney eventsMedian followPlasma sTNFR1Hazard ratioClinical outcomesKidney biomarkersPlasma biomarkersClinical covariatesSafety and Adequacy of Kidney Biopsy Procedure in Patients with Obesity
Qian L, Menez S, Hu D, Weinstein J, Melchinger H, Thiessen-Philbrook H, Luciano R, Turner J, Perazella M, Villalobos C, Shaw M, Wilson F, Parikh C, Moledina D. Safety and Adequacy of Kidney Biopsy Procedure in Patients with Obesity. Kidney360 2022, 4: 98-101. PMID: 36700910, PMCID: PMC10101611, DOI: 10.34067/kid.0006602022.Peer-Reviewed Original ResearchRole of time from transplantation to biopsy in histologic ABMR: A single center report
Chancay J, Liu C, Chauhan K, Andersen L, Harris C, Coca S, Delaney V, Tedla F, De Boccardo G, Sehgal V, Moledina D, Formica R, Reghuvaran A, Banu K, Florman S, Akalin E, Shapiro R, Salem F, Menon MC. Role of time from transplantation to biopsy in histologic ABMR: A single center report. Clinical Transplantation 2022, 36: e14802. PMID: 36069577, PMCID: PMC10211409, DOI: 10.1111/ctr.14802.Peer-Reviewed Original ResearchConceptsDeath-censored graft lossAntibody-Mediated RejectionDonor-specific antibodiesMicrovascular inflammationDQ-DSAAnti-human leukocyte antigen donor-specific antibodiesChronic allograft injurySingle-center reportsHigher inflammatory scoresCause biopsiesAllograft injuryGraft lossChronicity scoreInflammatory scoreHistologic factorsCT scoreFemale recipientsBiopsyMVI scoreT-scoreHeterogeneous etiologyCenter ReportTransplantationScoresSignificant correlationPlasma Soluble Tumor Necrosis Factor Receptor Concentrations and Clinical Events After Hospitalization: Findings From the ASSESS-AKI and ARID Studies
Coca SG, Vasquez-Rios G, Mansour SG, Moledina DG, Thiessen-Philbrook H, Wurfel MM, Bhatraju P, Himmelfarb J, Siew E, Garg AX, Hsu CY, Liu KD, Kimmel PL, Chinchilli VM, Kaufman JS, Wilson M, Banks RE, Packington R, McCole E, Kurth MJ, Richardson C, Go AS, Selby NM, Parikh CR. Plasma Soluble Tumor Necrosis Factor Receptor Concentrations and Clinical Events After Hospitalization: Findings From the ASSESS-AKI and ARID Studies. American Journal Of Kidney Diseases 2022, 81: 190-200. PMID: 36108888, PMCID: PMC9868060, DOI: 10.1053/j.ajkd.2022.08.007.Peer-Reviewed Original ResearchConceptsSoluble tumor necrosis factor receptor 1Acute kidney injuryHeart failureClinical eventsIndex hospitalizationPlasma soluble tumour necrosis factor receptor 1Soluble tumour necrosis factor receptor concentrationsBiomarker measurementsKidney disease incidenceBaseline serum samplesKidney disease progressionLate heart failureTumor necrosis factor receptor 1Association of biomarkersProportional hazards modelNecrosis factor receptor 1Magnitude of associationFactor receptor 1AKI statusIndex admissionKidney eventsKidney outcomesAKI definitionKidney injuryHospital dischargeUrine 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 modelMortality 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 activationClinically adjudicated deceased donor acute kidney injury and graft outcomes
Mansour SG, Khoury N, Kodali R, Virmani S, Reese PP, Hall IE, Jia Y, Yamamoto Y, Thiessen-Philbrook HR, Obeid W, Doshi MD, Akalin E, Bromberg JS, Harhay MN, Mohan S, Muthukumar T, Singh P, Weng FL, Moledina DG, Greenberg JH, Wilson FP, Parikh CR. Clinically adjudicated deceased donor acute kidney injury and graft outcomes. PLOS ONE 2022, 17: e0264329. PMID: 35239694, PMCID: PMC8893682, DOI: 10.1371/journal.pone.0264329.Peer-Reviewed Original ResearchConceptsDonor Acute Kidney InjuryAcute kidney injuryGraft failureAKI phenotypesKidney injuryUrine biomarkersLack of associationAKI casesGraft functionHigher DGFPotential kidneyGraft outcomeDeceased donorsOrgan utilizationMCP-1YKL-40Donor StudyEGFRDGFAncillary analysisAvailable chartsBiomarkersInjuryPhenotypeAssociation
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 nitrogenPrognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19
Menez S, Moledina DG, Thiessen-Philbrook H, Wilson FP, Obeid W, Simonov M, Yamamoto Y, Corona-Villalobos CP, Chang C, Garibaldi BT, Clarke W, Farhadian S, Dela Cruz C, Coca SG, Parikh CR, Investigators T, 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. Prognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19. American Journal Of Kidney Diseases 2021, 79: 257-267.e1. PMID: 34710516, PMCID: PMC8542781, DOI: 10.1053/j.ajkd.2021.09.008.Peer-Reviewed Original ResearchConceptsAdverse kidney outcomesNeutrophil gelatinase-associated lipocalinUrinary biomarkersBiomarker levelsKidney outcomesPrimary outcomeClinical AKIKidney injuryComposite outcomeCOVID-19KDIGO stage 3 AKIKidney injury molecule-1Cox proportional hazards regressionEpidermal growth factor levelsStage 3 AKIPrimary composite outcomeInjury molecule-1Kidney disease progressionGelatinase-associated lipocalinAdditional prognostic informationComposite outcome eventsProportional hazards regressionCOVID-19 patientsGrowth factor levelsCoronavirus disease 2019Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients
George S, Pal AC, Gagnon J, Timalsina S, Singh P, Vydyam P, Munshi M, Chiu JE, Renard I, Harden CA, Ott IM, Watkins AE, Vogels CBF, Lu P, Tokuyama M, Venkataraman A, Casanovas-Massana A, Wyllie AL, Rao V, Campbell M, Farhadian SF, Grubaugh ND, Dela Cruz CS, Ko AI, Perez A, Akaho EH, Moledina DG, Testani J, John AR, Ledizet M, Mamoun CB, Team A. Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients. Kidney360 2021, 2: 924-936. PMID: 35373072, PMCID: PMC8791366, DOI: 10.34067/kid.0002172021.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 spike proteinSARS-CoV-2Spike proteinUrine samplesSARS-CoV-2 infectionYale-New Haven HospitalCOVID-19 patientsAntigen capture assayDetectable viral RNANew Haven HospitalPositive PCR resultsPossible long-term consequencesSpike S1 proteinNP PCRChildren's HospitalNasopharyngeal swabsSARS-CoV-2 spike S1 proteinRenal abnormalitiesLong-term effectsCystatin CLong-term consequencesHospitalUrineViral RNAAlbuminuriaThe Challenges of Acute Interstitial Nephritis: Time to Standardize
Moledina DG, Perazella MA. The Challenges of Acute Interstitial Nephritis: Time to Standardize. Kidney360 2021, 2: 1051-1055. PMID: 35373086, PMCID: PMC8791367, DOI: 10.34067/kid.0001742021.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsHumansNephritis, Interstitial
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