2024
Volenrelaxin (LY3540378) increases Renal Plasma Flow: A Randomized Phase 1 Trial
San Tham L, Heerspink H, Wang X, Verdino P, Saifan C, Benson E, Goldsmith P, Wang Z, Testani J, Haupt A, Sam F, Cherney D. Volenrelaxin (LY3540378) increases Renal Plasma Flow: A Randomized Phase 1 Trial. Nephrology Dialysis Transplantation 2024, gfae112. PMID: 38782726, DOI: 10.1093/ndt/gfae112.Peer-Reviewed Original ResearchMeasured glomerular filtration rateEffective renal plasma flowRenal plasma flowKidney perfusionIncreased renal plasma flowPlacebo-adjusted changeMultiple-ascending dosePhase 1 trialGlomerular filtration rateChronic heart failureChronic kidney diseaseDiastolic blood pressureRenal arteriolar resistanceExtended half-lifeCardiorenal functionDouble-blindPlacebo SCRelaxin proteinSC doseAdverse eventsMeasured GFRArteriolar resistanceClinical developmentHeart failureOrthostatic hypotension
2023
Kidney and heart failure events are bidirectionally associated in patients with type 2 diabetes and cardiovascular disease
Sharma A, Inzucchi S, Testani J, Ofstad A, Fitchett D, Mattheus M, Verma S, Zannad F, Wanner C, Kraus B. Kidney and heart failure events are bidirectionally associated in patients with type 2 diabetes and cardiovascular disease. ESC Heart Failure 2023, 11: 737-747. PMID: 38155446, PMCID: PMC10966270, DOI: 10.1002/ehf2.14601.Peer-Reviewed Original ResearchPlacebo-treated participantsKidney eventsType 2 diabetesHeart failureCV eventsBaseline factorsLow-density lipoprotein cholesterol levelsMajor adverse CV eventsEMPA-REG OUTCOMEPrior heart failureAdverse CV eventsHeart failure eventsGlomerular filtration rateLipoprotein cholesterol levelsCoronary artery diseaseCox regression modelHigh uric acidUse of therapiesCardiovascular eventsCV diseaseHF outcomesArtery diseaseCholesterol levelsFiltration rateSubsequent riskAssociation of Urine Galectin-3 With Cardiorenal Outcomes in Patients With Heart Failure
Rao V, Ivey-Miranda J, Cox Z, Moreno-Villagomez J, Testani J. Association of Urine Galectin-3 With Cardiorenal Outcomes in Patients With Heart Failure. Journal Of Cardiac Failure 2023, 30: 340-346. PMID: 37301248, PMCID: PMC10947725, DOI: 10.1016/j.cardfail.2023.05.018.Peer-Reviewed Original ResearchGalectin-3 levelsHeart failureGalectin-3Renal fibrosisCardiac Function Heart FailureAldosterone Antagonist TrialContemporary HF cohortChronic kidney diseaseGlomerular filtration rateLow-risk phenotypeSignificant effect modificationLower eGFR levelsRenal tissue fibrosisAmino-terminal propeptideType III procollagenCardiorenal dysfunctionCardiorenal outcomesTOPCAT studyCause mortalityHF cohortSerum creatinineClinic cohortPrognostic importanceKidney diseasePrognostic indicatorThe blunted loop diuretic response in acute heart failure is driven by reduced tubular responsiveness rather than insufficient tubular delivery. The role of furosemide urine excretion on diuretic and natriuretic response in acute heart failure
Biegus J, Zymliński R, Testani J, Fudim M, Cox Z, Guzik M, Iwanek G, Hurkacz M, Raj D, Marciniak D, Ponikowska B, Ponikowski P. The blunted loop diuretic response in acute heart failure is driven by reduced tubular responsiveness rather than insufficient tubular delivery. The role of furosemide urine excretion on diuretic and natriuretic response in acute heart failure. European Journal Of Heart Failure 2023, 25: 1323-1333. PMID: 37042083, DOI: 10.1002/ejhf.2852.Peer-Reviewed Original ResearchConceptsAcute heart failureDiuretic responseHeart failureChronic usersTubular deliveryUrine volumeAcute heart failure patientsGlomerular filtration rateHeart failure patientsHigher urine volumeDiuretic exposureFurosemide deliveryFurosemide usersGood diuresisFurosemide doseFailure patientsNatriuretic responseFurosemide useTubular responseFiltration rateObservational studyUrine excretionNaïve groupHealthy individualsBody weightImprovement in Renal Function During the Treatment of Acute Decompensated Heart Failure: Relationship With Markers of Renal Tubular Injury and Prognostic Importance
Natov P, Ivey-Miranda J, Cox Z, Moreno-Villagomez J, Maulion C, Bellumkonda L, Shlipak M, Estrella M, Borlaug B, Rao V, Testani J. Improvement in Renal Function During the Treatment of Acute Decompensated Heart Failure: Relationship With Markers of Renal Tubular Injury and Prognostic Importance. Circulation Heart Failure 2023, 16: e009776. PMID: 36700431, PMCID: PMC10150783, DOI: 10.1161/circheartfailure.122.009776.Peer-Reviewed Original ResearchConceptsAcute decompensated heart failureDecompensated heart failureStable renal functionGlomerular filtration rateRenal functionRenal tubular injuryHeart failureTubular injuryKIM-1Filtration rateRenal tubular injury markersTubular injury markersRenal function groupCumulative urine outputCardiorenal dysfunctionDiuretic dosesInjury markersWorse survivalWorsened survivalUrine outputDecongestive therapyPrognostic importanceAdverse outcomesLower admissionPatients
2022
Evidence-Based Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Chronic Kidney Disease
Beldhuis IE, Lam CSP, Testani JM, Voors AA, Van Spall HGC, Maaten J, Damman K. Evidence-Based Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Chronic Kidney Disease. Circulation 2022, 145: 693-712. PMID: 35226558, PMCID: PMC9074837, DOI: 10.1161/circulationaha.121.052792.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsChronic kidney diseasePresence of CKDSevere chronic kidney diseaseHeart failure hospitalizationReduced ejection fractionHFrEF therapyHeart failureFailure hospitalizationEjection fractionMedical therapyKidney diseaseDrug classesSodium-glucose cotransporter 2 inhibitorsEvidence-based medical therapyGlucose cotransporter 2 inhibitorsStrong independent risk factorEnd pointCKD stage 3bPoor cardiovascular outcomesCKD stage 5Combined end pointCotransporter 2 inhibitorsIndependent risk factorSevere heart failureGlomerular filtration rate
2021
Rates of Reversal of Volume Overload in Hospitalized Acute Heart Failure: Association With Long-term Kidney Function
McCallum W, Tighiouart H, Testani JM, Griffin M, Konstam MA, Udelson JE, Sarnak MJ. Rates of Reversal of Volume Overload in Hospitalized Acute Heart Failure: Association With Long-term Kidney Function. American Journal Of Kidney Diseases 2021, 80: 65-78. PMID: 34843844, PMCID: PMC9135960, DOI: 10.1053/j.ajkd.2021.09.026.Peer-Reviewed Original ResearchConceptsB-type natriuretic peptideAcute heart failureEGFR declineHeart failureVolume overloadKidney functionNatriuretic peptideLower riskN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptideHeart Failure Outcome StudyLong-term kidney functionG4-G5Adverse kidney outcomesClinical congestion scoreKidney function declineGlomerular filtration rateCause-specific hazards modelKidney outcomesTolvaptan (EVEREST) trialCardiovascular outcomesVasopressin AntagonismImproved survivalFunction declineDecreased riskFGF-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 Hemodynamics and Renin-Angiotensin-Aldosterone System Profiles in Patients With Heart Failure
Lytvyn Y, Burns KD, Testani JM, Lytvyn A, Ambinathan JPN, Osuntokun O, Godoy LC, Cherney DZI, Parker JD. Renal Hemodynamics and Renin-Angiotensin-Aldosterone System Profiles in Patients With Heart Failure. Journal Of Cardiac Failure 2021, 28: 385-393. PMID: 34487814, DOI: 10.1016/j.cardfail.2021.08.015.Peer-Reviewed Original ResearchConceptsPlasma renin activityRenal blood flowAngiotensin converting enzymeHeart failureArteriolar resistanceGreater renal vascular resistanceEffective renal plasma flowRenal hemodynamic functionRenal vascular resistanceGlomerular filtration rateRenal plasma flowCardiorenal pathophysiologyGomez's equationsLower ERPFAldosterone systemIntravenous dobutamineNeurohormonal activationRenal hemodynamicsRenin activityVascular resistanceRenal profileRenin-AngiotensinHemodynamic functionLower GFRRenal veinRenal 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
2020
Renal profiling based on estimated glomerular filtration rate and spot urine sodium identifies high‐risk acute heart failure patients
Biegus J, Zymliński R, Testani J, Marciniak D, Zdanowicz A, Jankowska EA, Banasiak W, Ponikowski P. Renal profiling based on estimated glomerular filtration rate and spot urine sodium identifies high‐risk acute heart failure patients. European Journal Of Heart Failure 2020, 23: 729-739. PMID: 33190378, DOI: 10.1002/ejhf.2053.Peer-Reviewed Original ResearchConceptsAcute heart failureGlomerular filtration rateHeart failureFiltration rateDay 1Acute heart failure patientsHospital heart failureSpot urine sodiumHeart failure patientsUrinary sodium concentrationAHF patientsInotrope useTherapeutic profilingUrine sodiumFailure patientsIndependent prognosticatorRenal functionDay 2PatientsEGFRConcomitant assessmentWater handlingSodium concentrationPrognosticatorExcretersCystatin C and Muscle Mass in Patients With Heart Failure
Ivey-Miranda JB, Inker LA, Griffin M, Rao V, Maulion C, Turner JM, Wilson FP, Tang WHW, Levey AS, Testani JM. Cystatin C and Muscle Mass in Patients With Heart Failure. Journal Of Cardiac Failure 2020, 27: 48-56. PMID: 32750487, PMCID: PMC8672303, DOI: 10.1016/j.cardfail.2020.07.013.Peer-Reviewed Original ResearchConceptsHeart failureCreatinine clearanceMuscle massCystatin CHigher muscle massAssociation of eGFRcysGlomerular filtration rateLow muscle massCystatin C levelsAccurate GFR estimationMultivariable analysisFiltration rateEGFRcysEGFRcrBody compositionGFR estimationPatientsCreatinineC levelsClearanceMortalityAssociationAcute Kidney Function Declines in the Context of Decongestion in Acute Decompensated Heart Failure
McCallum W, Tighiouart H, Testani JM, Griffin M, Konstam MA, Udelson JE, Sarnak MJ. Acute Kidney Function Declines in the Context of Decongestion in Acute Decompensated Heart Failure. JACC Heart Failure 2020, 8: 537-547. PMID: 32535124, PMCID: PMC9027677, DOI: 10.1016/j.jchf.2020.03.009.Peer-Reviewed Original ResearchConceptsB-type natriuretic peptideAcute decompensated heart failureDecompensated heart failureHeart failureKidney functionAdverse outcomesAcute declineNT-proBNPComposite outcomeNatriuretic peptideHigh riskMultivariable Cox regression modelsTotal proteinAcute kidney functionMarkers of decongestionN-terminal prohormoneGlomerular filtration rateCox regression modelEGFR declineCardiovascular deathVolume overloadFiltration rateEGFRHospital changesDecongestionImproved cardiac and venous pressures during hospital stay in patients with acute heart failure: an echocardiography and biomarkers study
Akiyama E, Cinotti R, Čerlinskaitė K, Van Aelst LNL, Arrigo M, Placido R, Chouihed T, Girerd N, Zannad F, Rossignol P, Badoz M, Launay J, Gayat E, Cohen‐Solal A, Lam CSP, Testani J, Mullens W, Cotter G, Seronde M, Mebazaa A. Improved cardiac and venous pressures during hospital stay in patients with acute heart failure: an echocardiography and biomarkers study. ESC Heart Failure 2020, 7: 996-1006. PMID: 32277607, PMCID: PMC7261539, DOI: 10.1002/ehf2.12645.Peer-Reviewed Original ResearchConceptsLeft ventricular ejection fractionTricuspid annular plane systolic excursionNeutrophil Gelatinase-Associated LipocalinVenous pressureAHF patientsHFrEF patientsCardiac chamber dimensionsEchocardiographic parametersDyspnea patientsHeart failureNatriuretic peptidePlasma volumeMid-regional pro-atrial natriuretic peptideAcute heart failure patientsDiastolic Heart Failure StudyAnnular plane systolic excursionPro-atrial natriuretic peptideB-type natriuretic peptideE-wave deceleration timeInferior vena cava diameterAcute heart failureDiastolic heart failureGelatinase-Associated LipocalinGlomerular filtration rateHeart failure patientsEvaluation of kidney function throughout the heart failure trajectory – a position statement from the Heart Failure Association of the European Society of Cardiology
Mullens W, Damman K, Testani JM, Martens P, Mueller C, Lassus J, Tang WHW, Skouri H, Verbrugge FH, Orso F, Hill L, Ural D, Lainscak M, Rossignol P, Metra M, Mebazaa A, Seferovic P, Ruschitzka F, Coats A. Evaluation of kidney function throughout the heart failure trajectory – a position statement from the Heart Failure Association of the European Society of Cardiology. European Journal Of Heart Failure 2020, 22: 584-603. PMID: 31908120, DOI: 10.1002/ejhf.1697.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGlomerular filtration rateHeart failureKidney functionFiltration rateRenal functionSerum creatinineAcute heart failure episodeGuideline-directed medical therapyImproved long-term outcomesCardio-renal dysfunctionCardio-renal interactionsAcute heart failureChronic heart failureHeart Failure AssociationHeart failure careHeart failure stateHeart failure episodesAppropriate clinical contextLong-term outcomesRenal function assessmentFurther treatment strategiesNeurohumoral blockersLoop diureticsMedical therapyWorse outcomes
2019
Adverse Renal Response to Decongestion in the Obese Phenotype of Heart Failure With Preserved Ejection Fraction
Reddy YNV, Obokata M, Testani JM, Felker GM, Tang WHW, Abou-Ezzeddine OF, Sun JL, Chakrabothy H, McNulty S, Shah SJ, Lewis GD, Stevenson LW, Redfield MM, Borlaug BA. Adverse Renal Response to Decongestion in the Obese Phenotype of Heart Failure With Preserved Ejection Fraction. Journal Of Cardiac Failure 2019, 26: 101-107. PMID: 31618698, PMCID: PMC7036022, DOI: 10.1016/j.cardfail.2019.09.015.Peer-Reviewed Original ResearchConceptsRenal functionNonobese patientsHeart failureObese HFpEFObese patientsEjection fractionRenal responseAdverse renal responsesRight ventricular remodelingGlomerular filtration rateBody mass indexPlasma volume expansionSimilar weight lossCardiorenal hemodynamicsRenal dysfunctionPathophysiologic featuresMass indexAtrial fibrillationDecongestive therapyVentricular remodelingPericardial restraintFiltration rateHFpEFObese phenotypeSevere worsening
2018
Chronic kidney disease, worsening renal function and outcomes in a heart failure community setting: A UK national study
Lawson CA, Testani JM, Mamas M, Damman K, Jones PW, Teece L, Kadam UT. Chronic kidney disease, worsening renal function and outcomes in a heart failure community setting: A UK national study. International Journal Of Cardiology 2018, 267: 120-127. PMID: 29957251, PMCID: PMC6024224, DOI: 10.1016/j.ijcard.2018.04.090.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseRenal functionKidney diseasePrevalence of CKDModerate chronic kidney diseaseSevere chronic kidney diseasePresence of diabetesAdjusted risk estimatesGlomerular filtration rateCase-control studyHeart failure monitoringUK national studyHF prognosisFirst hospitalisationHF patientsRenal declineHF cohortRelated comorbiditiesHF settingFiltration rateNatural courseHospitalisationHigh riskRisk associationCommunity populationWorsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury
Ahmad T, Jackson K, Rao VS, Tang WHW, Brisco-Bacik MA, Chen HH, Felker GM, Hernandez AF, O'Connor CM, Sabbisetti VS, Bonventre JV, Wilson FP, Coca SG, Testani JM. Worsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury. Circulation 2018, 137: 2016-2028. PMID: 29352071, PMCID: PMC6066176, DOI: 10.1161/circulationaha.117.030112.Peer-Reviewed Original ResearchMeSH KeywordsAcetylglucosaminidaseAcute DiseaseAcute Kidney InjuryAgedAged, 80 and overBiomarkersCreatinineCystatin CDiuresisFemaleGlomerular Filtration RateHeart FailureHepatitis A Virus Cellular Receptor 1HumansKidneyLipocalin-2MaleMiddle AgedSodium Potassium Chloride Symporter InhibitorsTime FactorsTreatment OutcomeUnited StatesConceptsKidney injury molecule-1Neutrophil gelatinase-associated lipocalinInjury molecule-1Acute heart failureGelatinase-associated lipocalinRenal tubular injuryTubular injury biomarkersAggressive diuresisROSE-AHF trialsTubular injuryInjury biomarkersRenal functionHeart failureMolecule-1D-glucosaminidaseHigh-dose loop diuretic therapyAcute heart failure treatmentKidney tubular injuryLoop diuretic therapyAcute kidney injuryGlomerular filtration rateHeart failure treatmentDiuretic therapyFurosemide equivalentsKidney injury
2016
Reduced Cardiac Index Is Not the Dominant Driver of Renal Dysfunction in Heart Failure
Hanberg JS, Sury K, Wilson FP, Brisco MA, Ahmad T, Maaten J, Broughton JS, Assefa M, Tang WH, Parikh CR, Testani JM. Reduced Cardiac Index Is Not the Dominant Driver of Renal Dysfunction in Heart Failure. Journal Of The American College Of Cardiology 2016, 67: 2199-2208. PMID: 27173030, PMCID: PMC4867078, DOI: 10.1016/j.jacc.2016.02.058.Peer-Reviewed Original ResearchConceptsPulmonary artery catheterizationBlood urea nitrogenCardiac indexRenal functionHeart failureRenal dysfunctionGood renal functionReduced cardiac indexHigher cardiac indexGlomerular filtration rateSignificant inverse correlationMultiple subgroupsMulticenter populationWorse eGFRHF patientsCreatinine ratioArtery catheterizationPatient subgroupsFiltration rateSerial assessmentLinear mixed modelingESCAPE trialPatientsUrea nitrogenDysfunctionThe risk of death associated with proteinuria in heart failure is restricted to patients with an elevated blood urea nitrogen to creatinine ratio
Brisco MA, Zile MR, Maaten J, Hanberg JS, Wilson FP, Parikh C, Testani JM. The risk of death associated with proteinuria in heart failure is restricted to patients with an elevated blood urea nitrogen to creatinine ratio. International Journal Of Cardiology 2016, 215: 521-526. PMID: 27153048, PMCID: PMC4986924, DOI: 10.1016/j.ijcard.2016.04.100.Peer-Reviewed Original ResearchConceptsElevated blood urea nitrogenBUN/CrRenal dysfunctionBlood urea nitrogenCreatinine ratioUrea nitrogenLeft Ventricular Dysfunction (SOLVD) trialVentricular Dysfunction trialsGlomerular filtration rateRisk of deathBaseline characteristicsWorsened survivalAdverse eventsHeart failureTop tertileFiltration rateBottom tertileProteinuriaSurvival disadvantagePatientsMortalityTertileDysfunctionSurvivalSurvival models