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

https://doi.org/10.1016/j.cardfail.2021.08.015Get rights and content

Highlights

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    Patients with heart failure exhibit lower perfusion of the kidney compared to patients without heart failure.

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    Patients with heart failure have larger transrenal renin-angiotensin-aldosterone system marker gradients compared to controls without heart failure.

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    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.

Section snippets

Study Population

This was a post hoc exploratory analysis based on studies conducted at Mount Sinai Hospital, Toronto, Ontario, Canada, that involved stable outpatients with and without chronic HF secondary to left ventricular (LV) systolic dysfunction, a subset of which has been reported previously.12,13 All patients with HF were New York Heart Association class 2--3 and American College of Cardiology/American Heart Association stage C and had HF with reduced ejection fraction of ≤ 40%. Patients were enrolled

Baseline Characteristics and RAAS Markers

The cohorts were predominantly male (92% of patients with HF and 75% of patients without HF) and had a similar mean age of 57.3 ± 11.1 years in patients with HF and 57.3 ± 9.7 years in patients without HF. The ejection fraction in patients with HF was significantly reduced (23% ± 7%) compared to patients without HF (59% ± 9%). In patients with HF GFR (93 ± 26mL/min/1.73m2), ERPF (422 ± 132 mL/min/1.73m2), RBF (726 ± 231 mL/min/1.73m2) MAP (88 ± 17 mmHg), and systemic vascular resistance ((SVR)

Discussion

In the current analysis, our major observations were that (1) GFR, ERPF and RBF were lower in patients with HF vs non-HF without any significant differences being observed in afferent or efferent arteriolar resistances; (2) circulating levels of RAAS mediators, particularly aldosterone and PRA, were higher in the HF vs the non-HF group; (3) larger transrenal gradients for ACE, aldosterone and PRA levels were observed in patients with HF vs the group without HF; (4) transrenal gradients for RAAS

Limitations

Our work has important limitations. First, we recognize that although we used the transrenal gradient as a surrogate measure of intrarenal RAAS activation, we did not assess levels of RAAS activation directly in tissue. Therefore, a small portion of reported RAAS markers could be a result of activation/production in other tissues. For example, the venous samples were collected from the right renal vein, but the right adrenal vein has variable drainage, including into the renal vein; however, it

Lay Summary

We showed that patients with heart failure (HF) have a decreased supply of blood to the kidneys. Control of blood pressure in the body is regulated largely by the renin angiotensin aldosterone system (RAAS). In our group of patients with HF, there was a larger concentration of RAAS markers in blood vessels leaving the kidneys compared to the concentration of RAAS markers entering the kidneys. These data suggest that the kidneys in patients with heart failure may produce more RAAS markers,

Statement of Ethics

The Mount Sinai Hospital Research Ethics Board approved the protocol, and written informed consent was obtained from all participants (REB# 01-0259-U: Investigations Concerning the Control and Modulation of Renal and Cardiac Sympathetic Activity in Chronic Heart Failure).

Funding Sources

None

Authors’ Contributions

JDP and DZIC created the hypothesis and objectives, designed the study and prepared the manuscript; YL and KDB collected the data, researched the data and prepared the manuscript; JMTand AL researched the data and reviewed the manuscript; PNA, OO and LCG reviewed the manuscript; JDP and DZIC are the guarantors of this manuscript and, as such, had full access to all the data in the study and take responsibility for the integrity and accuracy of the data analysis.

Disclosures

DC is supported by a Department of Medicine, University of Toronto Merit Award and receives support from the CIHR, Diabetes Canada and the Heart and Stroke Richard Lewar Centre of Excellence and the Heart and Stroke Foundation of Canada.

DZIC has received consulting fees and speaking honoraria from Janssen, Boehringer Ingelheim-Eli, Lilly, AstraZeneca, Merck, and Sanofi and has received operating funds from Janssen, Boehringer Ingelheim-Eli, Lilly, AstraZeneca, and Merck; RA reports advisory

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    • Toronto and Ottawa, Ontario, Canada; New Haven, Connecticut; and Sao Paolo, Brazil

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    Co-senior/co-corresponding authors

    †

    Co-first authors that contributed equally.

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