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Brain natriuretic peptide as a potential novel marker of salt-sensitivity in chronic kidney disease patients without cardiac dysfunction

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Abstract

Although the renin–angiotensin system (RAS) is counter-balanced by a salt-sensitive mechanism in the hypertensive state, both are reported to be up-regulated in chronic kidney disease (CKD) patients. We conducted this study to evaluate the associations among the RAS, renal function, hypertension, and atherosclerosis, as well as to identify markers for salt-sensitivity. A total of 213 pre-dialysis CKD patients with preserved cardiac function (EF >50 %) were enrolled. Their renal and cardiac biochemical markers and plasma renin activity (PRA) were measured, and echocardiography and carotid artery ultrasound were performed. Their salt intake was estimated by the NaCl excretion from a 24-h collected urine sample. The PRA was higher in patients with hypertension (p = 0.018), and had a significant negative correlation with the eGFR (r = −0.23, p = 0.0067). Importantly, the PRA had a strong negative correlation with the brain natriuretic peptide (BNP) level (r = −0.28, p = 0.017) regardless of whether the patients were being treated with RAS inhibitors. The BNP level was related to the renal functions (eGFR: p = 0.001, ACR: p = 0.009). There was a significant positive correlation between the BNP level and carotid intima–media thickness (p < 0.001). A multivariate analysis revealed that older age and an excess of NaCl excretion were independent predictors of BNP elevation (p = 0.02 and 0.003, respectively). Our analysis revealed details of the counterbalance between BNP and PRA, as well as identifying that excess salt intake is a predictor of BNP elevation. These results indicate that the BNP could be a possible valuable marker for salt sensitivity, and that high salt sensitivity could facilitate atherosclerosis in CKD patients.

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Abbreviations

CKD:

Chronic kidney disease

eGFR:

Estimated glomerular filtration rate

PRA:

Plasma renin activity

BNP:

Brain natriuretic peptide

RAS:

Renin–angiotensin system

ACE-Is:

Angiotensin converting enzyme inhibitors

ARBs:

Angiotensin receptor blockers

EF:

Ejection fraction

LVMI:

Left ventricular mass index

ACR:

Albumin creatinine ratio

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Acknowledgments

The authors are indebted to all of the technicians, nurses, and doctors involve in the treatment of the CKD-specific outpatients for their ongoing support.

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Authors and Affiliations

  1. Department of Cardiology, Fujita Health University Banbuntane Hotokukai Hospital, 3-6-10 Otobashi, Nakagawa-ku, Nagoya, 454-8509, Japan

    Mutsuharu Hayashi, Manaka Tagaya, Takehiro Ito, Tomohito Kamada, Masataka Yoshinaga, Yoshinori Sugishita, Wakaya Fujiwara, Hiroatsu Yokoi & Hideo Izawa

  2. Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Mutsuharu Hayashi & Susumu Suzuki

  3. Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshinari Yasuda

  4. Department of Cardiology, Fujita Health University Hospital, Toyoake, Japan

    Yukio Ozaki

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  1. Mutsuharu Hayashi
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380_2016_867_MOESM1_ESM.jpg

Figure S1. Relationships among the PRA level, eGFR, hypertension, and use of RAS inhibitors. A. There was a significant negative correlation between the PRA and eGFR. B. There was a higher PRA level in patients with hypertension than in those without hypertension. C. The administration of RAS inhibitors led to up-regulation of the PRA level. HT: hypertension, RAS: RAS inhibitors (ACE-Is and/or ARBs) (JPEG 75 kb)

380_2016_867_MOESM2_ESM.jpg

Figure S2. Relationships among the BNP level, the renal function, and hypertension. A. There was a higher BNP level in patients with hypertension than in those without hypertension. B. There was a significant negative correlation between the BNP and eGFR. C. There was a significant positive correlation between the BNP and urinary ACR (JPEG 82 kb)

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Hayashi, M., Yasuda, Y., Suzuki, S. et al. Brain natriuretic peptide as a potential novel marker of salt-sensitivity in chronic kidney disease patients without cardiac dysfunction. Heart Vessels 32, 279–286 (2017). https://doi.org/10.1007/s00380-016-0867-1

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