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
2020
Pathophysiology of Diuretic Resistance and Its Implications for the Management of Chronic Heart Failure
Wilcox CS, Testani JM, Pitt B. Pathophysiology of Diuretic Resistance and Its Implications for the Management of Chronic Heart Failure. Hypertension 2020, 76: 1045-1054. PMID: 32829662, PMCID: PMC10683075, DOI: 10.1161/hypertensionaha.120.15205.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsChronic heart failureDiuretic resistanceHeart failureHigh daily salt intakeDiuretic-resistant patientsSequential nephron blockadeDaily salt intakeHypochloremic metabolic alkalosisLoop of HenleMultiple diureticsRenal nervesReflex activationLoop diureticsSalt intakeRecurrent hospitalizationsVolume overloadPathophysiological mechanismsSingle doseSodium outputMetabolic alkalosisPharmacokinetic mechanismsDistal tubulesDiureticsProximal tubulesRenal tubules
2017
Renal tubular resistance is the primary driver for loop diuretic resistance in acute heart failure
Maaten J, Rao VS, Hanberg JS, Wilson F, Bellumkonda L, Assefa M, Broughton J, D'Ambrosi J, Tang W, Damman K, Voors AA, Ellison DH, Testani JM. Renal tubular resistance is the primary driver for loop diuretic resistance in acute heart failure. European Journal Of Heart Failure 2017, 19: 1014-1022. PMID: 28105769, PMCID: PMC6231236, DOI: 10.1002/ejhf.757.Peer-Reviewed Original ResearchConceptsAcute heart failureLoop diuretic resistanceRenal tubular responseDiuretic resistanceDiuretic responseRenal tubulesAHF patientsHeart failureLoop diureticsTubular responseRenal tubular resistanceBumetanide doseEffective decongestionIntravenous bumetanidePoor outcomeUrine collectionTubular resistanceSum of defectsPatient variabilityUrea clearancePatientsCommon barriersDoseClearanceDiuretics