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Natriuretic peptides, extracellular volume, and subclinical cardiovascular changes in chronic kidney disease stages 1–3: a pilot study
  1. L Parker Gregg1,2,3,
  2. Peter N Van Buren4,5,
  3. David J Ramsey3,
  4. Amaris Maydon6,
  5. Subhash Banerjee7,8,
  6. Carl P Walther1,
  7. Salim S Virani3,9,10,
  8. Wolfgang C Winkelmayer1,
  9. Sankar D Navaneethan1,2,3,11,
  10. S Susan Hedayati4
  1. 1 Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
  2. 2 Medical Care Line, Section of Nephrology, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
  3. 3 Veterans Affairs Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Houston, Texas, USA
  4. 4 Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  5. 5 Medical Service, Renal Section, Veterans Affairs North Texas Health Care System, Dallas, Texas, USA
  6. 6 Mental Health Service, Veterans Affairs North Texas Health Care System, Dallas, Texas, USA
  7. 7 Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  8. 8 Medical Service, Cardiology Section, Veterans Affairs North Texas Health Care System, Dallas, Texas, USA
  9. 9 Internal Medicine, Section of Cardiology, Baylor College of Medicine, Houston, Texas, USA
  10. 10 Internal Medicine, Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
  11. 11 Institute of Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, USA
  1. Correspondence to Dr L Parker Gregg, Baylor College of Medicine Department of Medicine, Houston, Texas, USA; lucile.gregg{at}


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.

  • renal insufficiency, chronic
  • cardiovascular diseases
  • natriuretic peptides

Data availability statement

No data are available.

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  • Presented at These results were presented in part in abstract form at the American Society of Nephrology Kidney Week, October 22, 2020.

  • Contributors Study conception and design: LPG, PVB, SB, SSH; data collection: LPG, PVB, AM, SB, SSH; analysis and interpretation of results: LPG, PVB, DR, AM, SB, CW, SV, WW, SN, SSH; draft manuscript preparation: LPG, DR, SSH. All authors reviewed the results and approved the final version of the manuscript. LPG is responsible for the overall content as guarantor, accepts full responsibility for the finished work and the conduct of the study, had access to the data, and controlled the decision to publish.

  • Funding This study was funded in part by a VA North Texas Health Care System New Investigator Program award (awarded to LPG). LPG is supported by a VA CSR&D Career Development Award (IK2CX002368). This work was also supported in part by the Houston VA Health Services Research & Development Center for Innovations grant (CIN13-413). SSH is supported by the Yin Quan-Yuen Distinguished Professorship in Nephrology at the University of Texas Southwestern Medical Center, Dallas, Texas. CW is supported by grant K23DK122131 from the National Institute of Diabetes and Digestive and Kidney Diseases.

  • Disclaimer The interpretation and reporting of these data are the responsibility of the authors and in no way should be viewed as official policy or interpretation of the Department of Veterans Affairs or the US government.

  • 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,, 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.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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