Natriuretic Peptides, Extracellular Volume, and Subclinical Cardiovascular Changes in Chronic Kidney Disease Stages 1-3: a Pilot Study

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/cm/m, p=0.01) and lower cardiac index (2.28 (2.08-2.78) vs 3.08 (2.43-3.37) L/min/m, 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.