2023
Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes
Packer M, Wilcox C, Testani J. Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes. Circulation 2023, 148: 354-372. PMID: 37486998, PMCID: PMC10358443, DOI: 10.1161/circulationaha.123.064346.Peer-Reviewed Original ResearchConceptsSGLT2 inhibitorsProximal renal tubulesRenal tubulesProximal tubular effectHeart failure outcomesHeart failure eventsSodium-hydrogen exchanger 3Renal tubular sodiumProgressive volume lossLong-term treatmentReabsorption of glucoseTreatment-related changesChronic diuresisPharmacological toleranceTubular effectsClinical courseFractional excretionHeart failureTubular sodiumCardioprotective effectsRenal compensationDiuretic effectIndividual patientsDurable improvementDegree of upregulation
2022
Renin-Angiotensin-Aldosterone System Activation and Diuretic Response in Ambulatory Patients With Heart Failure
Amatruda JG, Scherzer R, Rao VS, Ivey-Miranda JB, Shlipak MG, Estrella MM, Testani JM. Renin-Angiotensin-Aldosterone System Activation and Diuretic Response in Ambulatory Patients With Heart Failure. Kidney Medicine 2022, 4: 100465. PMID: 35620081, PMCID: PMC9127684, DOI: 10.1016/j.xkme.2022.100465.Peer-Reviewed Original ResearchDiuretic doseTotal reninDiuretic responseDiuretic resistanceFractional excretionHeart failureActive reninSystem activationRenin-angiotensin-aldosterone system activationHigher plasmaActive renin levelsAldosterone system activationLower diuretic efficiencyPlasma total reninRAAS inhibitor useChronic heart failureMultivariable-adjusted modelsHigh-quality trialsLow fractional excretionFurosemide equivalentsRAAS blockadeAldosterone levelsRAAS activationRenin levelsInhibitor use
2021
FGF-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
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 excretionEffect of Loop Diuretics on the Fractional Excretion of Urea in Decompensated Heart Failure
Cox ZL, Sury K, Rao VS, Ivey-Miranda JB, Griffin M, Mahoney D, Gomez N, Fleming JH, Inker LA, Coca SG, Turner J, Wilson FP, Testani JM. Effect of Loop Diuretics on the Fractional Excretion of Urea in Decompensated Heart Failure. Journal Of Cardiac Failure 2020, 26: 402-409. PMID: 32007554, PMCID: PMC7798124, DOI: 10.1016/j.cardfail.2020.01.019.Peer-Reviewed Original ResearchConceptsAcute kidney injuryFractional excretionHeart failureLoop diureticsDecompensated heart failureFurosemide equivalentsKidney injuryProspective cohortDiuretic administrationDiuretic responsePeak diuresisDiuretic effectFEUreaDiureticsPatientsDiagnostic superiorityHospital systemExcretionMagnitude of changeDegree of changeBaselineDistribution of changesFENaDiuresisFailure
2017
Compensatory Distal Reabsorption Drives Diuretic Resistance in Human Heart Failure
Rao VS, Planavsky N, Hanberg JS, Ahmad T, Brisco-Bacik MA, Wilson FP, Jacoby D, Chen M, Tang WHW, Cherney DZI, Ellison DH, Testani JM. Compensatory Distal Reabsorption Drives Diuretic Resistance in Human Heart Failure. Journal Of The American Society Of Nephrology 2017, 28: 3414-3424. PMID: 28739647, PMCID: PMC5661276, DOI: 10.1681/asn.2016111178.Peer-Reviewed Original ResearchConceptsDiuretic resistanceHeart failureLoop diureticsSodium reabsorptionHigh-dose loop diureticsDistal tubular sodium reabsorptionSodium exitLoop diuretic administrationTubular sodium reabsorptionHuman heart failureFurosemide equivalentsDistal reabsorptionConsecutive patientsFractional excretionSodium handlingDiuretic administrationProximal tubularControl cohortCare centerTreatment strategiesAnimal modelsDiureticsNet sodiumFENaTubular location