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HFpEF in CKD is Associated with Elevated TNF‐α/IL‐6 Inflammatory Signaling from the Kidney
Author(s) -
Chade Alejandro R.,
Eirin Alfonso
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r3478
Subject(s) - medicine , cardiorenal syndrome , kidney disease , cardiology , heart failure , kidney , ejection fraction , renal function , diastole , heart failure with preserved ejection fraction , endocrinology , blood pressure
Background Chronic kidney disease (CKD) is independently associated with incident heart failure with preserved ejection fraction (HFpEF), but the underlying mechanisms remain unknown. We recently developed a translational swine model of CKD‐HF that replicates many features of human HFpEF. This study tested the hypothesis that CKD‐induced HFpEF associates with increased pro‐inflammatory cytokine signaling of renal origin. Methods CKD and normal pigs (n=4 each) were studied for 14 weeks. Renal hemodynamics (multi‐detector CT) and cardiac morphology and function (echocardiography) were quantified in vivo . Tumor necrosis factor (TNF)‐ α and interleukin (IL)‐6 levels (ELISA) were measured in circulating, renal vein, and coronary sinus blood, and their renal and cardiac gradients quantified. Systemic TNF‐α and IL‐6 levels (Luminex) were also measured in patients with CKD and age/gender‐matched healthy volunteers (n=12 each) and correlated with biomarkers of heart failure. Results Pigs with CKD developed hypertension, renal failure (stage 3), left ventricular (LV) hypertrophy, and abnormal LV strain and diastolic dysfunction (E/A, E/e’ ratio) with pEF, accompanied by positive renal (renal release) and negative cardiac (cardiac retention) gradients of TNF‐α and IL‐6 (Fig. 1A). Circulating TNF‐α and IL‐6 were also higher in patients with CKD compared to normal subjects (Fig. 1B), which correlated directly with ANP and NT‐proBNP levels (Fig. 1C). Conclusions Our experimental and clinical data supports a crosstalk between the kidney and the heart in CKD, suggesting that inflammatory signaling led by TNF‐α and IL‐6 of renal origin may impose cardiac abnormalities towards development of HFpEF.