2023
A 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 groupOutcomes 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 rateEmpagliflozin in Heart Failure: Regional Nephron Sodium Handling Effects
Rao V, Ivey-Miranda J, Cox Z, Moreno-Villagomez J, Maulion C, Bellumkonda L, Chang J, Field M, Wiederin D, Butler J, Collins S, Turner J, Wilson F, Inzucchi S, Wilcox C, Ellison D, Testani J. Empagliflozin in Heart Failure: Regional Nephron Sodium Handling Effects. Journal Of The American Society Of Nephrology 2023, 35: 189-201. PMID: 38073038, PMCID: PMC10843196, DOI: 10.1681/asn.0000000000000269.Peer-Reviewed Original ResearchThe importance of forward flow and venous congestion in diuretic response in acute heart failure: Insights from the ESCAPE trial
Eder M, Griffin M, Moreno-Villagomez J, Bellumkonda L, Maulion C, Asher J, Wilson F, Cox Z, Ivey-Miranda J, Rao V, Butler J, Borlaug B, McCallum W, Ramos-Mastache D, Testani J. The importance of forward flow and venous congestion in diuretic response in acute heart failure: Insights from the ESCAPE trial. International Journal Of Cardiology 2023, 381: 57-61. PMID: 37023862, DOI: 10.1016/j.ijcard.2023.04.002.Peer-Reviewed Original ResearchConceptsRight atrial pressureDiuretic efficiencyRight atrial areaDiuretic responseVenous congestionHeart failureCardio-renal interactionsLoop diuretic doseAcute heart failureRenal perfusion pressureLow cardiac outputMean arterial pressureRight ventricular systolicCongestive heart failureVentricular ejection fractionNet fluid outputForward flowDiuretic doseDiuretic resistanceTTE parametersCardiac indexVentricular systolicArterial pressureAtrial pressureEjection fractionIn-Hospital Observation on Oral Diuretics After Treatment for Acute Decompensated Heart Failure: Evaluating the Utility
Ivey-Miranda J, Rao V, Cox Z, Moreno-Villagomez J, Mahoney D, Maulion C, Bellumkonda L, Turner J, Collins S, Wilson F, Krumholz H, Testani J. In-Hospital Observation on Oral Diuretics After Treatment for Acute Decompensated Heart Failure: Evaluating the Utility. Circulation Heart Failure 2023, 16: e010206. PMID: 36896716, PMCID: PMC10186250, DOI: 10.1161/circheartfailure.122.010206.Peer-Reviewed Original ResearchConceptsAcute decompensated heart failureDecompensated heart failureDiuretic responseDiuretic dosingOral diureticsHeart failureMulticenter cohortHospital observationLower readmission ratesNet fluid balanceDays postdischargeReadmission ratesHospital readmissionUrine outputReadmission riskFluid statusFluid balanceHospital measuresDose selectionCohortProvider decisionsWeight changeReadmissionDiureticsPatients
2022
Mortality 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 activationHemoconcentration of Creatinine Minimally Contributes to Changes in Creatinine during the Treatment of Decompensated Heart Failure
Maulion C, Chen S, Rao VS, Ivey-Miranda JB, Cox ZL, Mahoney D, Coca SG, Negoianu D, Asher JL, Turner JM, Inker LA, Wilson FP, Testani JM. Hemoconcentration of Creatinine Minimally Contributes to Changes in Creatinine during the Treatment of Decompensated Heart Failure. Kidney360 2022, 3: 1003-1010. PMID: 35845336, PMCID: PMC9255871, DOI: 10.34067/kid.0007582021.Peer-Reviewed Original ResearchInferior Vena Cava Diameter Measurement Provides Distinct and Complementary Information to Right Atrial Pressure in Acute Decompensated Heart Failure
Griffin M, Ivey-Miranda J, McCallum W, Sarnak M, Eder M, Bellumkonda L, Maulion C, Wilson FP, Rao VS, Testani J. Inferior Vena Cava Diameter Measurement Provides Distinct and Complementary Information to Right Atrial Pressure in Acute Decompensated Heart Failure. Journal Of Cardiac Failure 2022, 28: 1217-1221. PMID: 35301109, DOI: 10.1016/j.cardfail.2022.02.014.Peer-Reviewed Original ResearchConceptsRight atrial pressureAcute decompensated heart failureDecompensated heart failureIVC diameterAtrial pressureHeart failureInferior vena cava diameter (IVCD) measurementBaseline right atrial pressureInferior vena cava (IVC) measurementsPulmonary artery catheterVena cava diameter measurementsArtery catheterHemoglobin levelsIntravascular volumeVenous systemESCAPE trialIVC measurementsBlood volumeRAP measurementsSurvival ratePatientsVolume assessmentHigh complianceModest correlationMedian
2021
The 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 levelsNatriuretic Equation to Predict Loop Diuretic Response in Patients With Heart Failure
Rao VS, Ivey-Miranda JB, Cox ZL, Riello R, Griffin M, Fleming J, Soucier R, Sangkachand P, O'Brien M, LoRusso F, D'Ambrosi J, Churchwell K, Mahoney D, Bellumkonda L, Asher JL, Maulion C, Turner JM, Wilson FP, Collins SP, Testani JM. Natriuretic Equation to Predict Loop Diuretic Response in Patients With Heart Failure. Journal Of The American College Of Cardiology 2021, 77: 695-708. PMID: 33573739, PMCID: PMC8114781, DOI: 10.1016/j.jacc.2020.12.022.Peer-Reviewed Original ResearchConceptsLoop diuretic administrationDiuretic therapyNatriuretic responseDiuretic administrationSodium outputAcute decompensated heart failureDecompensated heart failureHeart failure admissionsDaily urine outputSpot urine samplesNet fluid outputNet fluid lossPathway cohortHeart failureLoop diureticsUrine outputDiuretic responseResidual congestionFluid outputTherapyCohortWeight lossAdditional studiesUrine samplesExcellent discriminationElectronic health record alerts for acute kidney injury: multicenter, randomized clinical trial
Wilson FP, Martin M, Yamamoto Y, Partridge C, Moreira E, Arora T, Biswas A, Feldman H, Garg AX, Greenberg JH, Hinchcliff M, Latham S, Li F, Lin H, Mansour SG, Moledina DG, Palevsky PM, Parikh CR, Simonov M, Testani J, Ugwuowo U. Electronic health record alerts for acute kidney injury: multicenter, randomized clinical trial. The BMJ 2021, 372: m4786. PMID: 33461986, PMCID: PMC8034420, DOI: 10.1136/bmj.m4786.Peer-Reviewed Original ResearchConceptsAcute kidney injuryElectronic health record alertsKidney injuryPrimary outcomeMedical recordsYale New Haven Health SystemCare practicesGlobal Outcomes creatinine criteriaLarge tertiary care centerComposite of progressionDays of randomizationReceipt of dialysisPrespecified secondary outcomesTertiary care centerPatients' medical recordsSmall community hospitalNon-teaching hospitalsElectronic health recordsCreatinine criteriaUsual careSecondary outcomesAdult inpatientsKidney diseaseClinical centersWorse outcomesFGF-23 (Fibroblast Growth Factor-23) and Cardiorenal Interactions
Ivey-Miranda JB, Stewart B, Cox ZL, McCallum W, Maulion C, Gleason O, Meegan G, Amatruda JG, Moreno-Villagomez J, Mahoney D, Turner JM, Wilson FP, Estrella MM, Shlipak MG, Rao VS, Testani JM. FGF-23 (Fibroblast Growth Factor-23) and Cardiorenal Interactions. Circulation Heart Failure 2021, 14: e008385. PMID: 34689571, PMCID: PMC8782627, DOI: 10.1161/circheartfailure.121.008385.Peer-Reviewed Original ResearchConceptsFGF-23Cardiorenal interactionsHeart failureDiuretic resistanceSodium avidityNeurohormonal activationMultivariable analysisDistal tubular sodium reabsorptionLoop diuretic doseTubular sodium reabsorptionGlomerular filtration rateCardiorenal dysfunctionDiuretic doseDiuretic treatmentNT-proBNPFractional excretionDiuretic administrationSodium reabsorptionPeak diuresisFiltration rateCare centerUrine samplingAnimal modelsSerum chlorideDisease severityRenal negative pressure treatment as a novel therapy for heart failure-induced renal dysfunction
Rao VS, Maulion C, Asher JL, Ivey-Miranda J, Cox ZL, Moreno-Villagomez J, Mahoney D, Turner JM, Wilson FP, Wilcox CS, Testani J. Renal negative pressure treatment as a novel therapy for heart failure-induced renal dysfunction. AJP Regulatory Integrative And Comparative Physiology 2021, 321: r588-r594. PMID: 34405731, DOI: 10.1152/ajpregu.00115.2021.Peer-Reviewed Original ResearchConceptsRenal plasma flowGlomerular filtration rateCongestive HFTubular pressureHeart failure hospitalizationPara-aminohippurate clearanceCentral venous pressureHigh fractional excretionNegative pressure therapyUrinary collecting systemNegative pressure treatmentSimilar diuresisFailure hospitalizationRenal dysfunctionCardiac tamponadeIothalamate clearanceFractional excretionRenal parametersKidney functionRenal congestionRenal responseRight kidneyVenous pressurePressure therapyControl kidneys
2024
COVID-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 declineEarly, Individualized Recommendations for Hospitalized Patients With Acute Kidney Injury
Aklilu A, Menez S, Baker M, Brown D, Dircksen K, Dunkley K, Gaviria S, Farrokh S, Faulkner S, Jones C, Kadhim B, Le D, Li F, Makhijani A, Martin M, Moledina D, Coronel-Moreno C, O’Connor K, Shelton K, Shvets K, Srialluri N, Tan J, Testani J, Corona-Villalobos C, Yamamoto Y, Parikh C, Wilson F, Sundararajan A, Wang A, Schretlen C, Singel D, Moss E, Aune F, Iantosca G, Zou G, Chernova I, Bitzel J, Hernandez J, Lindsley J, Dane K, Orias M, Mehta P, Zassman-Isner S, Wen Y, Freeman N. Early, Individualized Recommendations for Hospitalized Patients With Acute Kidney Injury. JAMA 2024, 332 PMID: 39454050, DOI: 10.1001/jama.2024.22718.Peer-Reviewed Original ResearchElectronic health recordsUsual careHealth recordsAction teamsClinicians of patientsHospitalized patientsFinal follow-upIntervention groupHealth systemStudy pharmacistsStudy physiciansMain OutcomesAssociated with adverse outcomesAcute kidney injuryRandomized clinical trialsPrimary outcomeIndividualized recommendationsNew HavenAdverse outcomesAKI detectionCareRhode IslandComposite outcomeFollow-upInterventionMechanistic Differences between Torsemide and Furosemide.
Rao V, Cox Z, Ivey-Miranda J, Neville D, Balkcom N, Moreno-Villagomez J, Ramos-Mastache D, Maulion C, Bellumkonda L, Tang W, Collins S, Velazquez E, Mentz R, Wilson F, Turner J, Wilcox C, Ellison D, Fang J, Testani J. Mechanistic Differences between Torsemide and Furosemide. Journal Of The American Society Of Nephrology 2024 PMID: 39196651, DOI: 10.1681/asn.0000000000000481.Peer-Reviewed Original ResearchTorsemide groupDiuretic doseTubular site of actionHigher diuretic dosesDose of furosemideProportion of dosesOral furosemideSite of actionPrescribed doseNeurohormonal activationMechanistic substudyClinical outcomesPharmacodynamic advantagesKidney dysfunctionPharmacodynamic parametersKidney functionRandomized trialsNatriuresisTubular sitesFurosemideTorsemideDoseTRANSFORM-HFPlasma volumeBody weightSerial direct sodium removal in patients with heart failure and diuretic resistance
Rao V, Ivey‐Miranda J, Cox Z, Moreno‐Villagomez J, Ramos‐Mastache D, Neville D, Balkcom N, Asher J, Bellumkonda L, Bigvava T, Shaburishvili T, Bartunek J, Wilson F, Finkelstein F, Maulion C, Turner J, Testani J. Serial direct sodium removal in patients with heart failure and diuretic resistance. European Journal Of Heart Failure 2024, 26: 1215-1230. PMID: 38556717, DOI: 10.1002/ejhf.3196.Peer-Reviewed Original ResearchConceptsDiuretic resistanceCardiorenal syndromeHeart failureLoop diureticsDiuretic withdrawalHigh-dose loop diureticsN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptideGrowth differentiation factor 15Carbohydrate antigen 125Differentiation factor 15Sodium removalRandomized controlled studyCardiorenal parametersDiuretic doseSoluble ST2Natriuretic peptideMedian timeDiuretic responseKidney injuryPeritoneal membraneElectrolyte handlingKidney functionDiureticsInterleukin-6
2020
Real-Time Prediction of Acute Kidney Injury in Hospitalized Adults: Implementation and Proof of Concept
Ugwuowo U, Yamamoto Y, Arora T, Saran I, Partridge C, Biswas A, Martin M, Moledina DG, Greenberg JH, Simonov M, Mansour SG, Vela R, Testani JM, Rao V, Rentfro K, Obeid W, Parikh CR, Wilson FP. Real-Time Prediction of Acute Kidney Injury in Hospitalized Adults: Implementation and Proof of Concept. American Journal Of Kidney Diseases 2020, 76: 806-814.e1. PMID: 32505812, PMCID: PMC8667815, DOI: 10.1053/j.ajkd.2020.05.003.Peer-Reviewed Original ResearchConceptsAKI alertsHospitalized adultsKidney injuryUrban tertiary care hospitalAcute kidney injurySerum creatinine levelsObservational cohort studyTertiary care hospitalSerum creatinine concentrationBeats/minElectronic health recordsAKI diagnosisCohort studyCreatinine levelsInpatient mortalitySystolic bloodFractional excretionCenter studyBlood biomarkersUnivariable associationsUrine microscopyCreatinine concentrationClinical careElevated riskUrea nitrogenEmpagliflozin in Heart Failure
Griffin M, Rao VS, Ivey-Miranda J, Fleming J, Mahoney D, Maulion C, Suda N, Siwakoti K, Ahmad T, Jacoby D, Riello R, Bellumkonda L, Cox Z, Collins S, Jeon S, Turner JM, Wilson FP, Butler J, Inzucchi SE, Testani JM. Empagliflozin in Heart Failure. Circulation 2020, 142: 1028-1039. PMID: 32410463, PMCID: PMC7521417, DOI: 10.1161/circulationaha.120.045691.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter 2 inhibitorsCotransporter 2 inhibitorsNeurohormonal activationHeart failureRenal dysfunctionBlood volumeHeart failure-related outcomesPlacebo-controlled crossover studyType 2 diabetes mellitusProximal tubular siteHeart failure outcomesStable heart failureUrinary glucose excretionUric acid levelsElectrolyte wastingEmpagliflozin monotherapyOral empagliflozinPlacebo periodStudy drugGlucose excretionNatriuretic effectPotassium wastingTubular sitesDiabetes mellitusFractional excretionReal World Use of Hypertonic Saline in Refractory Acute Decompensated Heart Failure A U.S. Center’s Experience
Griffin M, Soufer A, Goljo E, Colna M, Rao VS, Jeon S, Raghavendra P, D'Ambrosi J, Riello R, Coca SG, Mahoney D, Jacoby D, Ahmad T, Chen M, Tang WHW, Turner J, Mullens W, Wilson FP, Testani JM. Real World Use of Hypertonic Saline in Refractory Acute Decompensated Heart Failure A U.S. Center’s Experience. JACC Heart Failure 2020, 8: 199-208. PMID: 32035891, PMCID: PMC7814403, DOI: 10.1016/j.jchf.2019.10.012.Peer-Reviewed Original ResearchConceptsAcute decompensated heart failureHypertonic saline administrationHypertonic saline therapyHypertonic salineSaline administrationSaline therapyDiuretic efficiencyUrine outputSerum sodiumWeight lossAcute decompensated heartDecompensated heart failureCohort of patientsTotal urine outputReal-world safetyU.S. academic medical centersAcademic medical centerLarge U.S. academic medical centerDiuretic doseCenter experienceHeart failureMetabolic derangementsPrimary analytic approachRespiratory statusClinical variables