Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study

Abstract

BackgroundLeft ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function.MethodsPlasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory.ResultsLVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin- creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 [95% CI 1.16, 1.37], p<0.001), IL-1RA (1.23 [1.13, 1.34], p<0.0001), IL-6 (1.25 [1.14, 1.36], p<0.001) and TNF-α (1.14 [1.04, 1.25], p = 0.004) were associated with LVH. The odds for systolic dysfunction were greater for subjects with elevated levels of hs-CRP (1.32 [1.18, 1.48], p<0.001) and IL-6 (1.34 [1.21, 1.49], p<0.001). Only hs-CRP was associated with diastolic dysfunction (1.14 [1.04, 1.26], p = 0.005).ConclusionIn patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction.

Janus Face of Coronary Artery Disease and Chronic Kidney Disease

“…Findings from the Chronic Renal Insufficiency Cohort study showed that plasma levels of pro‐inflammatory cytokines and positive acute‐phase proteins were higher in subjects with lower levels of kidney function 12. We showed that specific inflammatory biomarkers are associated with cardiac geometry and risk of atrial fibrillation in patients with CKD 13, 14. Potential causes of inflammation in CKD include chronic subclinical infections, volume overload, increased oxidative stress, sympathetic overactivity, poor nutrition, and vitamin D deficiency, which are also risk factors for CVD.…”

Association of Left Ventricular Hypertrophy With a Faster Rate of Renal Function Decline in Elderly Patients With Non‐End‐Stage Renal Disease

“…(2) Long‐term LVH can induce left ventricular dysfunction and decrease blood perfusion in the glomeruli, resulting in renal tubular ischemia. (3) In patients with LVH, the associated inflammatory response, indicated by, for example, elevated plasma levels of high‐sensitivity C‐reactive protein and interleukin‐6, may contribute to and accelerate the progression of systolic dysfunction and cause rapid progression of CKD …”

“…LVH emerges as an adaptive response to overload, such as pressure or volume, to some extent, but long‐term LVH leads to left ventricular dysfunction, resulting in the constriction of the renal arteries, less blood‐perfusion of the glomeruli, and alteration of the glomerular membrane filtration coefficient and tubular reabsorption . The inflammatory response associated with LVH also contributes to the progression of CKD . Thus, LVH appears to be a type of adverse cardiac remodeling that contributes to risk factors of CKD.…”

The systemic nature of CKD

“…Persistent sympathetic activation can trigger cardiac hypertrophy and fibrosis through activation of the immune system 58 . Accordingly, in patients with stage 3-5 CKD, concentric left ventricular hypertrophy is associated with inflammation 70,71 and with high levels of noradrenaline 72 and neuro peptide Y 73 . High levels of these biomarkers underlie high cardiovascular risk in CKD 74,75 .…”