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. 2022 Jul 19:jim-2022-002467.
doi: 10.1136/jim-2022-002467. Online ahead of print.

Natriuretic peptides, extracellular volume, and subclinical cardiovascular changes in chronic kidney disease stages 1-3: a pilot study

L Parker Gregg  1   2   3 , Peter N Van Buren  4   5 , David J Ramsey  3 , Amaris Maydon  6 , Subhash Banerjee  7   8 , Carl P Walther  9 , Salim S Virani  3   10   11 , Wolfgang C Winkelmayer  9 , Sankar D Navaneethan  9   2   3   12 , S Susan Hedayati  4
Affiliations

Natriuretic peptides, extracellular volume, and subclinical cardiovascular changes in chronic kidney disease stages 1-3: a pilot study

L Parker Gregg et al. J Investig Med. .

Abstract

Natriuretic peptide levels are elevated in persons with chronic kidney disease (CKD) stages 1-3, but it remains unclear whether this is associated with extracellular volume excess or early cardiovascular changes. We hypothesized that patients with CKD stages 1-3 would have evidence of cardiovascular changes, which would associate with brain natriuretic peptide (BNP), amino-terminal-pro-BNP (NT-pro-BNP), and patient-reported symptoms.Outpatients with CKD stages 1-3 and non-CKD controls were enrolled. Cardiovascular parameters included extracellular water (ECW) normalized to body weight measured using whole-body multifrequency bioimpedance spectroscopy, and total peripheral resistance index (TPRI) and cardiac index measured by impedance cardiography. Dyspnea, fatigue, depression, and quality of life were quantified using questionnaires.Among 21 participants (13 with CKD), median (IQR) BNP was 47.0 (28.0-302.5) vs 19.0 (12.3-92.3) pg/mL, p=0.07, and NT-pro-BNP was 245.0 (52.0-976.8) vs 26.0 (14.5-225.8) pg/mL, p=0.08, in the CKD and control groups, respectively. Those with CKD had higher pulse pressure (79 (66-87) vs 64 (49-67) mm Hg, p=0.046) and TPRI (3721 (3283-4278) vs 2933 (2745-3198) dyn×s/cm5/m2, p=0.01) and lower cardiac index (2.28 (2.08-2.78) vs 3.08 (2.43-3.37) L/min/m2, p=0.02). In the overall cohort, natriuretic peptides correlated with pulse pressure (BNP r=0.59; NT-pro-BNP r=0.58), cardiac index (BNP r=-0.76; NT-pro-BNP r=-0.62), and TPRI (BNP r=0.48), p<0.05 for each, but not with ECW/weight. TPRI and blood pressure correlated moderately with symptoms.Elevated natriuretic peptides may coincide with low cardiac index and elevated peripheral resistance in patients with CKD stages 1-3. The role of these biomarkers to detect subclinical cardiovascular changes needs to be further explored.

Keywords: cardiovascular diseases; natriuretic peptides; renal insufficiency, chronic.

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Conflict of interest statement

Competing interests: PNVB is an associate editor for the Journal of Investigative Medicine. SN reports receiving personal fees from AstraZeneca (Data Safety Monitoring Board) Bayer, Boehringer Ingelheim, and Eli Lilly and Co and Vifor; receiving grants from Keryx and receiving research funding from the Department of Veterans Affairs Health Services Research & Development outside the submitted work. SV reports research funding from VA HSR&D, NIH, World Heart Federation, Tahir, and Jooma Family; and honoraria from the American College of Cardiology in his role as the Associate Editor for Innovations, acc.org, outside of this work. WW reports personal fees from Akebia/Otsuka, AstraZeneca, Bayer, Boehringer-Ingelheim/Lilly, GlaxoSmithKline, Janssen, Merck, Pharmacosmos, and Reata, outside of this work. The remaining authors have nothing to disclose.

Figures

Figure 1.
Figure 1.. CKD was associated with higher pulse pressure, lower cardiac index, and higher peripheral resistance.
Dot plots show the individual data points for BNP (A), NT-pro-BNP (B), systolic blood pressure (C), diastolic blood pressure (D), pulse pressure (E), ECW/total body weight (F), cardiac index (G), and TPRI (H). Abbreviations: BNP, brain natriuretic peptide; BP, blood pressure; CKD, chronic kidney disease; ECW, extracellular water; NT-pro-BNP, amino terminal pro-BNP; TPRI, total peripheral resistance index
Figure 2.
Figure 2.. BNP and NT-pro-BNP were associated with cardiovascular parameters.
Scatterplots show the linear associations of BNP with pulse pressure (A), cardiac index (B), and TPRI (C) and of NT-pro-BNP with pulse pressure (D) and cardiac index (E). Natriuretic peptides and blood pressure values were measured the same day as the available cardiac index and total peripheral resistance index measurement for each participant. Abbreviations: BNP, brain natriuretic peptide; CKD, chronic kidney disease; NT-pro-BNP, amino terminal pro-BNP; TPRI, total peripheral resistance index *P<0.05 **P<0.01
Figure 3.
Figure 3.. Higher systolic and diastolic blood pressure and higher peripheral resistance may be associated with multiple patient-reported symptoms.
In an exploratory analysis, the heat map represents correlations seen between symptom scores and cardiovascular parameters, with bright red representing the strongest positive correlations and bright blue representing the strongest negative correlations. Pale red and pale blue represent weaker correlations, and gray represents correlations near zero. Patient-reported symptoms, ECW/total body weight, and blood pressure were measured the same day as the available cardiac index and total peripheral resistance index measurement for each participant. Abbreviations: FACIT-F, Functional Assessment of Chronic Illness Therapy – Fatigue; KDQOL, Kidney Disease Health Related Quality of Life-Short Form 36; QIDS-SR16, 16-item Self-Reported Quick Inventory of Depressive Symptomatology; TPRI, total peripheral resistance index
Figure 4.
Figure 4.. Repeated measurements of natriuretic peptides and extracellular volume were consistent over time.
BNP (A), NT-pro-BNP (B), and ECW/total body weight (C) were consistent within participants from baseline to follow-up 4 weeks later. Abbreviations: BNP, brain natriuretic peptide; CKD, chronic kidney disease; ECW, extracellular water; NT-pro-BNP, amino terminal pro-BNP
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