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Renal Hemodynamics and Renin-Angiotensin-Aldosterone System Profiles in Patients With Heart Failure

  • Author Footnotes
    † Co-first authors that contributed equally.
    YULIYA Lytvyn
    Correspondence
    Reprint requests: Yuliya Lytvyn, PhD, Toronto General Hospital, 585 University Avenue, 12N-1215, Toronto, Ontario M5G 2N2, Canada.
    Footnotes
    † Co-first authors that contributed equally.
    Affiliations
    Toronto General Hospital Research Institute, Toronto, Ontario, Canada

    Department of Medicine, Division of Nephrology, University of Toronto, Toronto, Ontario, Canada
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  • Author Footnotes
    † Co-first authors that contributed equally.
    KEVIN D. BURNS
    Footnotes
    † Co-first authors that contributed equally.
    Affiliations
    Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
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  • JEFFREY M. TESTANI
    Affiliations
    Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut
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  • ANDRIY LYTVYN
    Affiliations
    Toronto General Hospital Research Institute, Toronto, Ontario, Canada
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  • JAYA PRAKASH N. AMBINATHAN
    Affiliations
    Toronto General Hospital Research Institute, Toronto, Ontario, Canada
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  • OLUWATOSIN OSUNTOKUN
    Affiliations
    Peter Munk Cardiac Centre and the Heart and Stroke Richard Lewar Centre, University of Toronto, Ontario, Canada
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  • LUCAS C. GODOY
    Affiliations
    Toronto General Hospital Research Institute, Toronto, Ontario, Canada

    Peter Munk Cardiac Centre and the Heart and Stroke Richard Lewar Centre, University of Toronto, Ontario, Canada

    Instituto do Coracao, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
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  • Author Footnotes
    # Co-senior/co-corresponding authors
    DAVID Z.I. CHERNEY
    Footnotes
    # Co-senior/co-corresponding authors
    Affiliations
    Toronto General Hospital Research Institute, Toronto, Ontario, Canada

    Department of Medicine, Division of Nephrology, University of Toronto, Toronto, Ontario, Canada

    Banting and Best Diabetes Centre, Toronto, Canada

    Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
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  • Author Footnotes
    # Co-senior/co-corresponding authors
    JOHN D. PARKER
    Footnotes
    # Co-senior/co-corresponding authors
    Affiliations
    Peter Munk Cardiac Centre and the Heart and Stroke Richard Lewar Centre, University of Toronto, Ontario, Canada

    Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada

    Department of Medicine, Division of Cardiology, Sinai Health System and Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada
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  • Author Footnotes
    # Co-senior/co-corresponding authors
    † Co-first authors that contributed equally.
Published:September 03, 2021DOI:https://doi.org/10.1016/j.cardfail.2021.08.015

      Highlights

      • Patients with heart failure exhibit lower perfusion of the kidney compared to patients without heart failure.
      • Patients with heart failure have larger transrenal renin-angiotensin-aldosterone system marker gradients compared to controls without heart failure.
      • Such renal origin of neurohormonal activation may be associated with renal vasoconstriction and lower perfusion of the kidney in patients with heart failure.

      ABSTRACT

      Objective

      Understanding cardiorenal pathophysiology in heart failure (HF) is of clinical importance. We sought to characterize the renal hemodynamic function and the transrenal gradient of the renin-angiotensin-aldosterone system (RAAS) markers in patients with HF and in controls without HF.

      Methods

      In this post hoc analysis, the glomerular filtration rate (GFRinulin), effective renal plasma flow (ERPFPAH) and transrenal gradients (arterial-renal vein) of angiotensin converting enzyme (ACE), aldosterone, and plasma renin activity (PRA) were measured in 47 patients with HF and in 24 controls. Gomez equations were used to derive afferent (RA) and efferent (RE) arteriolar resistances. Transrenal RAAS gradients were also collected in patients treated with intravenous dobutamine (HF, n = 11; non-HF, n = 11) or nitroprusside (HF, n = 18; non-HF, n = 5).

      Results

      The concentrations of PRA, aldosterone and ACE were higher in the renal vein vs the artery in patients with HF vs patients without HF (P < 0.01). In patients with HF, a greater ACE gradient was associated with greater renal vascular resistance (r = 0.42; P 0.007) and greater arteriolar resistances (RA: r = 0.39; P = 0.012; RE: r = 0.48; P = 0.002). Similarly, a greater aldosterone gradient was associated with lower GFR (r = –0.51; P = 0.0007) and renal blood flow (RBF), r = –0.32; P = 0.042) whereas greater PRA gradient with lower ERPF (r = –0.33; P = 0.040), GFR (r = –0.36; P = 0.024), and RBF (r = –0.33; P = 0.036). Dobutamine and nitroprusside treatment decreased the transrenal gradient of ACE (P = 0.012, P < 0.0001, respectively), aldosterone (P = 0.005, P = 0.030) and PRA (P = 0.014, P = 0.002) in patients with HF only.

      Conclusions

      A larger transrenal RAAS marker gradient in patients with HF suggests a renal origin for neurohormonal activation associated with a vasoconstrictive renal profile.

      Key Words

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